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Huang YC, Lee NY, Weng MY. Increased risk of Pneumocystis jirovecii colonization in rheumatoid arthritis patients on biologics and Janus kinase inhibitor. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2025; 58:112-119. [PMID: 39271438 DOI: 10.1016/j.jmii.2024.08.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 08/15/2024] [Accepted: 08/26/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND The prevalence of Pneumocystis jirovecii (PJ) pneumonia among rheumatic patients is rising. PJ colonization serves as a reservoir for transmission and precedes the development of PJ pneumonia. We aim to clarify the association of PJ colonization in patients of rheumatoid arthritis (RA) treated with biologics or Janus kinase inhibitors (JAKi). METHODS A prospective cohort study was performed from March 2021 to July 2022 in the rheumatology outpatient department of National Cheng Kung University Hospital. We obtained oral-wash samples from asymptomatic RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and JAKi. A real-time quantitative polymerase chain reaction assay focusing on the mitochondrial large subunit ribosomal ribonucleic acid gene of PJ was applied to detect colonization. RESULTS One hundred and ten RA patients were enrolled. Adjusted odds ratios (ORs) of PJ colonization were 6.40 (95% CI 1.34-30.57, p-value =0.02) in patients receiving bDMARDs or JAKi. Specifically, in patients treated with bDMARDs the adjusted OR was 8.08 (95% CI 1.57-41.51, p-value=0.012), and a trend toward developing PJ colonization was further identified in patients receiving JAKi (adjusted OR: 4.79, 95% CI 0.89-25.91, p=0.069). Among patients treated with bDMARDs or JAKi, medication duration >3 years and age >60 y/o are risk factors for PJ colonization. CONCLUSION RA patients on bDMARDs or JAK inhibitors have an approximately 6-fold higher risk of developing P. jirovecii colonization. Patients treated with bDMARDs had an 8-fold higher risk of P. jirovecii colonization. Risk factors of PJ colonization are medication duration >3 years and age > 60 y/o.
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Affiliation(s)
- Ya-Chun Huang
- Department of Internal Medicine, Division of Allergy, Immunology, and Rheumatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| | - Nan-Yao Lee
- Department of Internal Medicine and Center for Infection Control, National Cheng Kung University Hospital and Medical College, Tainan, Taiwan.
| | - Meng-Yu Weng
- Department of Internal Medicine, Division of Allergy, Immunology, and Rheumatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Nishimura K, Ishikawa T, Okamoto N, Akamine K, Inoue N, Irabu H, Kato K, Keino H, Kojima M, Kubo H, Maruyama K, Mizuta M, Shabana K, Shimizu M, Sugita Y, Takakuwa Y, Takanashi S, Takase H, Umebayashi H, Umezawa N, Yamanishi S, Yamazaki K, Yashiro M, Yasumi T, Mori M. Efficacy and safety of abatacept for systemic juvenile idiopathic arthritis: A systematic review. Mod Rheumatol 2024; 35:167-173. [PMID: 38753302 DOI: 10.1093/mr/roae046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 05/08/2024] [Indexed: 12/28/2024]
Abstract
OBJECTIVES This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA). METHODS Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan. RESULTS Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6, and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9%, and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms, and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases. CONCLUSIONS Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL-6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms.
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Affiliation(s)
- Kenichi Nishimura
- Department of Pediatrics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
| | - Takashi Ishikawa
- Division of Immunology, National Center for Child Health and Development, Tokyo, Japan
- Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan
| | - Nami Okamoto
- Department of Pediatrics, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Keiji Akamine
- Department of Nephrology and Rheumatology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Natsumi Inoue
- Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Ishikawa, Japan
| | - Hitoshi Irabu
- Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kentaro Kato
- Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hiroshi Keino
- Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
| | | | - Hiroshi Kubo
- Department of Pediatrics, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| | - Kazuichi Maruyama
- Department of Vision Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Mao Mizuta
- Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children's Hospital, Hyogo, Japan
| | - Kosuke Shabana
- Department of Pediatrics, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Masaki Shimizu
- Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuko Sugita
- Department of Pediatrics, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Yukiko Takakuwa
- Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Satoshi Takanashi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hiroshi Takase
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiroaki Umebayashi
- Department of Rheumatism, Infectious Disease, Miyagi Children's Hospital, Miyagi, Japan
| | - Natsuka Umezawa
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shingo Yamanishi
- Department of Pediatrics, Tokyo Yamate Medical Center, Tokyo, Japan
| | - Kazuko Yamazaki
- Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Masato Yashiro
- Department of Pediatrics, Okayama University Hospital, Okayama, Japan
| | - Takahiro Yasumi
- Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Masaaki Mori
- Lifetime Clinical Immunology, Tokyo Medical and Dental University, Tokyo, Japan
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Ishikawa T, Nishimura K, Okamoto N, Akamine K, Inoue N, Irabu H, Kato K, Keino H, Kojima M, Kubo H, Maruyama K, Mizuta M, Shabana K, Shimizu M, Sugita Y, Takakuwa Y, Takanashi S, Takase H, Umebayashi H, Umezawa N, Yamanishi S, Yamazaki K, Yashiro M, Yasumi T, Mori M. Efficacy and safety of tumor necrosis factor inhibitors for systemic juvenile idiopathic arthritis: A systematic review. Mod Rheumatol 2024; 35:174-184. [PMID: 38795057 DOI: 10.1093/mr/roae050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 04/16/2024] [Accepted: 05/22/2024] [Indexed: 05/27/2024]
Abstract
OBJECTIVES This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA). METHODS Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual of Minds for observational studies. RESULTS One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 [95% confidence interval (CI): 0.94-1.79]/1.48 (95% CI: 0.95-2.29)/1.89 (95% CI: 0.81-4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection, and malignancy caused by TNF inhibitors was 0-4%. CONCLUSIONS Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, especially well-designed RCTs, are needed to accumulate clinical data.
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Affiliation(s)
- Takashi Ishikawa
- Division of Immunology, National Center for Child Health and Development, Tokyo, Japan
- Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan
| | - Kenichi Nishimura
- Department of Pediatrics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
| | - Nami Okamoto
- Department of Pediatrics, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Keiji Akamine
- Department of Nephrology and Rheumatology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Natsumi Inoue
- Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Ishikawa, Japan
| | - Hitoshi Irabu
- Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kentaro Kato
- Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hiroshi Keino
- Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
| | | | - Hiroshi Kubo
- Department of Pediatrics, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| | - Kazuichi Maruyama
- Department of Vision Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Mao Mizuta
- Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children's Hospital, Hyogo, Japan
| | - Kosuke Shabana
- Department of Pediatrics, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Masaki Shimizu
- Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuko Sugita
- Department of Pediatrics, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Yukiko Takakuwa
- Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Satoshi Takanashi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hiroshi Takase
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiroaki Umebayashi
- Department of Rheumatism, Infectious Disease, Miyagi Children's Hospital, Miyagi, Japan
| | - Natsuka Umezawa
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shingo Yamanishi
- Department of Pediatrics, Tokyo Yamate Medical Center, Tokyo, Japan
| | - Kazuko Yamazaki
- Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Masato Yashiro
- Department of Pediatrics, Okayama University Hospital, Okayama, Japan
| | - Takahiro Yasumi
- Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Masaaki Mori
- Lifetime Clinical Immunology, Tokyo Medical and Dental University, Tokyo, Japan
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Miyashiro M, Asano T, Ishii Y, Miyazaki C, Shimizu H, Masuda J. Treatment Patterns of Biologic Disease-Modifying Antirheumatic Drugs and Janus Kinase Inhibitors in Patients with Rheumatoid Arthritis in Japan: A Claims-Based Cohort Study. Drugs Real World Outcomes 2024; 11:285-297. [PMID: 38598110 PMCID: PMC11176134 DOI: 10.1007/s40801-024-00423-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/13/2024] [Indexed: 04/11/2024] Open
Abstract
BACKGROUND Reports on treatment patterns of biologic disease-modifying antirheumatic drugs (bDMARDs)/Janus kinase inhibitors (JAKi) for rheumatoid arthritis (RA) in clinical practice are still sparse in Japan, especially in combination with conventional synthetic DMARDs (csDMARDs). OBJECTIVES The aim of this study was to investigate treatment patterns of bDMARD/JAKi in the treatment of RA in real-world clinical practice in Japan. METHOD A retrospective cohort study was conducted using the Japanese Medical Data Vision health claims database. The inclusion criteria required a recorded diagnosis of RA, defined by ICD-10 codes, in patients aged 18 years and older on the index date. We analyzed 39,903 RA patients treated with DMARDs from 2008 to 2020. RESULTS Among analyzed subjects, 10,196 patients (25.6%) were prescribed bDMARDs/JAKi in combination with csDMARDs, and 3067 patients (7.7%) were prescribed these drugs without csDMARDs. Among the bDMARDs/JAKi, tumor necrosis factor inhibitors (TNFi) were the most commonly prescribed DMARD overall, and also the most common first-line therapy, accounting for 60.0% or 45.5% of patients prescribed these drugs in combination with or without csDMARDs, respectively. Switching, temporary discontinuation (restarting with the same agents), and discontinuation of bDMARDs/JAKi were observed in 3150 (30.9%), 1379 (13.5%), and 2025 (19.9%) patients with csDMARDs, and in 849 (27.7%), 513 (16.7%), and 833 (27.2%) patients without csDMARDs, respectively. CONCLUSIONS Real-world treatment trajectories of bDMARDs/JAKi with and without csDMARDs was analyzed in RA patients in Japan between 2008 and 2020. TNFi were the predominant first-line therapy, and likely to be switched to different classes. Understanding the current treatment patterns, including discontinuation, is important to find an optimal treatment strategy for RA patients.
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Affiliation(s)
- Masahiko Miyashiro
- Immunology and Infectious Diseases Department, Medical Affairs Division, Janssen Pharmaceutical K.K., Nishi Kanda 3-5-2, Chiyoda-Ku, Tokyo, 101-0065, Japan
| | - Teita Asano
- Immunology and Infectious Diseases Department, Medical Affairs Division, Janssen Pharmaceutical K.K., Nishi Kanda 3-5-2, Chiyoda-Ku, Tokyo, 101-0065, Japan.
| | - Yutaka Ishii
- Immunology and Infectious Diseases Department, Medical Affairs Division, Janssen Pharmaceutical K.K., Nishi Kanda 3-5-2, Chiyoda-Ku, Tokyo, 101-0065, Japan
| | - Celine Miyazaki
- Value, Evidence and Access Department, Janssen Pharmaceutical K.K., Nishi Kanda 3-5-2, Chiyoda-Ku, Tokyo, 101-0065, Japan
| | - Hirohito Shimizu
- Medical Affairs Division, Medical Excellence Department, Janssen Pharmaceutical K.K., Nishi Kanda 3-5-2, Chiyoda-Ku, Tokyo, 101-0065, Japan
| | - Junya Masuda
- Immunology and Infectious Diseases Department, Medical Affairs Division, Janssen Pharmaceutical K.K., Nishi Kanda 3-5-2, Chiyoda-Ku, Tokyo, 101-0065, Japan
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Noguchi H, Takeichi T, Hayai S, Yoshikawa M, Muro Y, Akiyama M. Pneumocystis pneumonia in a patient with severe generalized pustular psoriasis treated with biologics. J Dermatol 2024; 51:e112-e114. [PMID: 37905597 DOI: 10.1111/1346-8138.17014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 09/19/2023] [Accepted: 10/10/2023] [Indexed: 11/02/2023]
Affiliation(s)
- Haruka Noguchi
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takuya Takeichi
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shunsaku Hayai
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masato Yoshikawa
- Division of Dermatology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
| | - Yoshinao Muro
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masashi Akiyama
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Harigai M, Fujii T, Sakai R, Igarashi A, Shoji A, Yamaguchi H, Iwasaki K, Makishima M, Yoshida A, Okada N, Yamashita K, Kawahito Y. Risk of hospitalized infections in older elderly patients with rheumatoid arthritis treated with tocilizumab or other biological/targeted synthetic disease-modifying antirheumatic drugs: Evaluation of data from a Japanese claims database. Mod Rheumatol 2024; 34:287-296. [PMID: 37039670 DOI: 10.1093/mr/road031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 03/15/2023] [Indexed: 04/12/2023]
Abstract
OBJECTIVE We compared the incidence rates of hospitalized infections (HIs) between tocilizumab (TCZ) and other biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in adults aged ≥75 years with rheumatoid arthritis (RA). METHODS We used a Japanese claims database from Medical Data Vision Co., Ltd (Tokyo, Japan) to perform a retrospective longitudinal population-based study in patients with RA who were prescribed b/tsDMARDs between 2014 and 2019. We calculated adjusted risk ratios (aRRs) for HIs in three age groups (<65, ≥65 and <75, and ≥75 years). RESULTS Of 5506 patients, 2265 (41.1%) were <65 years, 1709 (31.0%) were 65-74 years, and 1532 (27.8%) were ≥75 years. Crude incidence rates (/100 person-years) of HIs were 3.99, 7.27, and 10.77, respectively. In the oldest group, aRRs (95% confidence interval) for HIs (b/tsDMARDs versus TCZ) were as follows: etanercept, 2.40 (1.24-4.61); adalimumab, 1.90 (0.75-4.83); golimumab, 1.21 (0.66-2.23); and abatacept, 0.89 (0.49-1.62). In the other age groups, the noticeable difference was a lower aRR of etanercept versus TCZ in the youngest group (0.30, 0.11-0.85). CONCLUSION In patients with RA aged ≥75 years, b/tsDMARDs have a similar risk of HIs to tocilizumab except for etanercept.
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Affiliation(s)
- Masayoshi Harigai
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Takao Fujii
- Department of Rheumatology and Clinical Immunology, Wakayama Medical University, Wakayama, Japan
| | - Ryoko Sakai
- Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Tokyo, Japan
| | - Ataru Igarashi
- Department of Health Economics & Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
- Unit of Public Health and Preventive Medicine, Yokohama City University of Medicine, Yokohama, Japan
| | - Ayako Shoji
- Medilead Inc., Tokyo Opera City Tower, Tokyo, Japan
| | | | | | | | | | | | | | - Yutaka Kawahito
- Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Kuwana M, Sugiyama N, Momohara S, Atsumi T, Takei S, Tamura N, Harigai M, Fujii T, Matsuno H, Takeuchi T, Yamamoto K, Takasaki Y, Tanigawa M, Endo Y, Hirose T, Morishima Y, Yoshii N, Mimori T, Takagi M. Six-month safety and effectiveness of tofacitinib in patients with rheumatoid arthritis in Japan: Interim analysis of post-marketing surveillance. Mod Rheumatol 2024; 34:272-286. [PMID: 37405710 DOI: 10.1093/mr/road063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 06/17/2023] [Indexed: 07/06/2023]
Abstract
OBJECTIVES We evaluated the real-world safety/effectiveness of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), in patients with RA in Japan registered in a post-marketing surveillance study. METHODS This interim analysis included data from July 2013 to December 2018. Adverse events (AEs), serious AEs (SAEs), Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] scores, and rates of SDAI/CDAI/DAS28-4(ESR)-defined remission and low disease activity were analysed using 6 months of data. Risk factors for serious infections were assessed by multivariable analyses. RESULTS Safety and disease activity were evaluated in 6866 and 6649 patients, respectively. Overall, 32.73%/7.37% of patients reported AEs/SAEs. Clinically important AEs with tofacitinib included serious infections/infestations [3.13% of patients; incidence rate (IR; patients with events) 6.91/100 patient-years (PY)], herpes zoster (3.63%; IR 8.02/100 PY), and malignancies (0.68%; IR 1.45/100 PY). SDAI/CDAI/DAS28-4(ESR) scores and remission/low disease activity rates improved over 6 months. Male sex, older age, Steinbrocker's stage IV, history of infection, and diabetes mellitus at baseline were independent risk factors for serious infection. CONCLUSIONS In patients with RA receiving tofacitinib in Japan, safety was consistent with the reported profile, and disease activity improved over 6 months. STUDY IDENTIFIER NCT01932372.
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Affiliation(s)
- Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
| | - Naonobu Sugiyama
- Inflammation and Immunology Medical Affairs, Pfizer Japan Inc., Tokyo, Japan
| | - Shigeki Momohara
- Kusanagi Orthopedic Rheumatology Clinic, Shizuoka, Japan
- Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Tatsuya Atsumi
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Syuji Takei
- Pediatric Rheumatology, Medical Center for Children, Kagoshima University Hospital, Kagoshima, Japan
| | - Naoto Tamura
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | - Masayoshi Harigai
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Takao Fujii
- Department of Rheumatology and Clinical Immunology, Wakayama Medical University, Wakayama, Japan
| | | | - Tsutomu Takeuchi
- Department of Rheumatology, Keio University School of Medicine, Tokyo, Japan
- Saitama Medical University, Saitama, Japan
| | | | - Yoshinari Takasaki
- Juntendo Koshigaya Hospital, Juntendo University Faculty of Medicine, Saitama, Japan
| | | | | | - Tomohiro Hirose
- Inflammation and Immunology Medical Affairs, Pfizer Japan Inc., Tokyo, Japan
| | - Yosuke Morishima
- Inflammation and Immunology Medical Affairs, Pfizer Japan Inc., Tokyo, Japan
| | - Noritoshi Yoshii
- Inflammation and Immunology Medical Affairs, Pfizer Japan Inc., Tokyo, Japan
| | | | - Michiaki Takagi
- Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan
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Matsumoto T, Sugihara T, Hosoya T, Ishizaki T, Kubo K, Kamiya M, Baba H, Tsuchida M, Hirano F, Kojima M, Miyasaka N, Harigai M. Effectiveness and safety of treat-to-target strategy for methotrexate-naïve rheumatoid arthritis patients >75 years of age. Rheumatol Adv Pract 2024; 8:rkae019. [PMID: 38425693 PMCID: PMC10904149 DOI: 10.1093/rap/rkae019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 01/24/2024] [Indexed: 03/02/2024] Open
Abstract
Objectives To identify differences in effectiveness and safety of a treat-to-target (T2T) strategy comparing late-onset MTX-naïve RA patients (LORA) ≥75 or <75 years of age. Methods Treatment was adjusted to target low disease activity with conventional synthetic DMARDs followed by biologic DMARDs (bDMARDs) in LORA ≥75 years (n = 98, mean age 80.0 years) and LORA <75 years (n = 99) with moderate-high disease activity. Achievement of Simplified Disease Activity Index (SDAI) remission at week 156 by non-responder imputation analysis was evaluated as a primary outcome. Results LORA ≥75 years had more comorbidities than LORA <75 years, but SDAI and ACPA positivity were similar at baseline. Of the LORA ≥75 years, 70.4% started MTX and 34.1% and 37.1% received a bDMARD at week 52 and 156, respectively (very similar to the LORA <75 years). Glucocorticoid use was more frequent in the LORA ≥75 years than in the LORA <75 years. Comorbidities/adverse events more frequently contributed to the reasons for non-adherence to T2T in the LORA ≥75 than in the LORA <75. At week 156, 32.7% of the LORA ≥75 and 66.7% of the LORA <75 achieved SDAI remission (P < 0.001). The cumulative incidence of serious adverse events (SAEs) over 156 weeks was 42.8% in the LORA ≥75 and 22.1% in the LORA <75. Multivariable analysis indicated an increased risk of SDAI non-remission at week 156 in the LORA ≥75 [odds ratio 2.82 (95% CI 1.29. 6.14)] after adjusting for comorbidities at baseline, non-adherence to T2T and SAEs. Conclusions It was more difficult to achieve remission in the LORA ≥75 patients than in the LORA <75 patients due to both poor treatment response and safety issues.
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Affiliation(s)
- Takumi Matsumoto
- Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Takahiko Sugihara
- Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
- Human Care Research Team, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
- Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan
| | - Tadashi Hosoya
- Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tatsuro Ishizaki
- Human Care Research Team, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
| | - Kanae Kubo
- Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
| | - Mari Kamiya
- Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiroyuki Baba
- Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Marina Tsuchida
- Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Fumio Hirano
- Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masayo Kojima
- Department of Frailty Research, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Obu, Japan
| | - Nobuyuki Miyasaka
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masayoshi Harigai
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan
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9
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Yanagihara T, Oka Y, Moriwaki A, Moriuchi Y, Ogata H, Ishimatsu A, Otsuka J, Taguchi K, Yoshida M. A Case of Pneumocystis Pneumonia Developed During Rheumatoid Arthritis Treatment With Methotrexate and Golimumab. Cureus 2024; 16:e52944. [PMID: 38406039 PMCID: PMC10894044 DOI: 10.7759/cureus.52944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2024] [Indexed: 02/27/2024] Open
Abstract
Here, we report a case of an 87-year-old female patient with rheumatoid arthritis (RA) treated with methotrexate (MTX) and golimumab who developed severe pneumocystis pneumonia (PCP), also known as Pneumocystis jirovecii pneumonia. The patient presented with chief complaints of dyspnea on exertion, dry cough, and fatigue. A high-resolution chest CT scan revealed diffuse, unevenly distributed ground-glass opacities throughout both lungs. The patient was clinically diagnosed with PCP based on the clinical settings, imaging, and a high level of serum β-D-glucan. While the patient required high-flow oxygen therapy, low-dose trimethoprim/sulfamethoxazole and corticosteroid therapy improved her condition, and the patient was discharged on day 25. Although to our knowledge no case report has been published regarding PCP in patients with RA treated with golimumab, this case emphasizes the importance of attention to opportunistic infections in elderly patients receiving immunosuppressive therapy. MTX use alongside tumor necrosis factor inhibitors like golimumab may increase the risk of serious infections such as PCP. The case underscores the necessity of prophylactic measures and early intervention for PCP, highlighting the delicate balance between immunosuppression benefits and infection risks in RA management.
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Affiliation(s)
- Toyoshi Yanagihara
- Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JPN
| | - Yusuke Oka
- Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JPN
| | - Atushi Moriwaki
- Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JPN
| | - Yuki Moriuchi
- Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JPN
| | - Hiroaki Ogata
- Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JPN
| | - Akiko Ishimatsu
- Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JPN
| | - Junji Otsuka
- Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JPN
| | - Kazuhito Taguchi
- Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JPN
| | - Makoto Yoshida
- Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JPN
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10
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Sumi T, Takeda K, Michimata H, Nagayama D, Koshino Y, Watanabe H, Yamada Y, Kodama K, Nishikiori H, Chiba H. Pneumocystis Pneumonia Infection Following the Initiation of Pembrolizumab Therapy for Lung Adenocarcinoma. Intern Med 2023; 62:3381-3385. [PMID: 37005268 DOI: 10.2169/internalmedicine.1163-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/03/2023] Open
Abstract
Pneumocystis pneumonia (PCP) is an opportunistic infection that presents a ground-glass appearance in the lungs on chest radiography. Interstitial lung disease is a commonly reported adverse effect of immune checkpoint inhibitor (ICI) treatment; however, there are few reports of ICI treatment-associated PCP infection. A 77-year-old man with lung adenocarcinoma was administered pembrolizumab and hospitalized for dyspnea 2 weeks after treatment. Chest computed tomography showed bilateral ground-glass opacities in all lung lobes. PCP was therefore diagnosed, and steroids and sulfamethoxazole-trimethoprim were initiated. Following treatment, the patient's condition improved promptly. This report suggests that ICI treatment can cause PCP infection.
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Affiliation(s)
- Toshiyuki Sumi
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, Japan
| | - Kazuya Takeda
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan
| | - Haruhiko Michimata
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, Japan
| | - Daiki Nagayama
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, Japan
| | - Yuta Koshino
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, Japan
| | - Hiroki Watanabe
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, Japan
| | - Yuichi Yamada
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, Japan
| | - Kentaro Kodama
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan
| | - Hirotaka Nishikiori
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan
| | - Hirofumi Chiba
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan
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11
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Takabayashi K, Ando F, Ikeda K, Nakajima H, Hanaoka H, Suzuki T. Incidence of opportunistic infections in patients with rheumatoid arthritis treated with different molecular-targeted drugs: A population-based retrospective cohort study. Mod Rheumatol 2023; 33:1078-1086. [PMID: 36308397 DOI: 10.1093/mr/roac133] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 10/23/2022] [Indexed: 11/08/2023]
Abstract
OBJECTIVES We compared the incidences of four opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with molecular-targeted drugs from big claims data. MATERIALS AND METHODS We identified 205,906 patients with RA who were prescribed molecular-targeted drugs in 2010-17 from the National Database of Japan and calculated the incidence of four OIs (Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster). RESULTS The total number of Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster patients with biological disease-modifying antirheumatic drugs or tofacitinib treatment history in RA was 765, 1158, 834, and 18,336, respectively. The incidence rates of each OI for all biological disease-modifying antirheumatic drugs were 0.14, 0.14, 0.09, and 2.40 per 100 person-years, respectively, while for tofacitinib they were 0.22, 0.22, 0.07, and 7.00 per 100 person-years. No big difference was observed among biological disease-modifying antirheumatic drugs. All OIs showed higher incidence in those >65 years, but Pneumocystis pneumonia, nontuberculous mycobacterial infection, and herpes zoster showed no difference between those 65-74 years old and those >75 years old. The median of occurrence was the third, seventh, ninth, and thirteenth month after treatment, respectively. CONCLUSIONS We counted real incidence rates of OIs for the whole nation from big claims data.
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Affiliation(s)
- Katsuhiko Takabayashi
- Division of Medical Informatics and Management, Chiba University Hospital, Chiba, Japan
- Department of Internal Medicine, Sanwa Hospital, Chiba, Japan
| | - Fumihiko Ando
- Division of Medical Informatics and Management, Chiba University Hospital, Chiba, Japan
| | - Kei Ikeda
- Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan
| | - Hiroshi Nakajima
- Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan
| | - Hideki Hanaoka
- Clinical Research Center, Chiba University Hospital, Chiba, Japan
| | - Takahiro Suzuki
- Division of Medical Informatics and Management, Chiba University Hospital, Chiba, Japan
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12
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Chen J, Liao J, Xiang L, Zhang S, Yan Y. Current knowledge of TNF-α monoclonal antibody infliximab in treating Kawasaki disease: a comprehensive review. Front Immunol 2023; 14:1237670. [PMID: 37936712 PMCID: PMC10626541 DOI: 10.3389/fimmu.2023.1237670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 10/10/2023] [Indexed: 11/09/2023] Open
Abstract
Kawasaki disease (KD), an autoinflammatory disease primarily affecting young children, characterized by consisting of acute systemic vasculitis and coronary artery involvement in severe cases. Intravenous immunoglobulin gamma (IVIG) combined with aspirin therapy is the first-line regimen for the prevention of coronary aneurysms in the acute phase of KD. The etiology and pathogenesis of KD are unclear, but its incidence is increasing gradually, especially in the cases of IVIG-naïve KD and refractory KD. Conventional therapies for refractory KD have unsatisfactory results. At present, infliximab (IFX), a human-murine chimeric monoclonal antibody that specifically blocks tumor necrosis factor-α (TNF-α), has made great progress in the treatment of KD. This review revealed that IFX infusion (5 mg/kg) could effectively modulate fever, reduce inflammation, improve arthritis, diminish the number of plasma exchange, decrease hospitalizations, and prevent the progression of coronary artery lesions. The adverse effects of IFX administration included skin rash, arthritis, respiratory disease, infusion reaction, hepatomegaly, and vaccination-associated complications. But the incidence of these adverse effects is low. The clear optimal application protocol of the application of IFX for either initial combination therapy or salvage therapy in KD is still under investigation. In addition, there are no effective biomarkers to predict IFX resistance. Further multicenter trials with large sample size and long-term follow-up are still needed to validate the clinical efficacy and safety of IFX for IVIG-resistant KD or refractory KD.
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Affiliation(s)
- Jiaying Chen
- Department of Pediatrics, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Jian Liao
- Department of Nephrology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, China
| | - Lupeng Xiang
- Taizhou University Medical School, Taizhou, Zhejiang, China
| | - Shilong Zhang
- Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yajing Yan
- Health Management Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
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13
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Harrington R, Harkins P, Conway R. Targeted Therapy in Rheumatoid-Arthritis-Related Interstitial Lung Disease. J Clin Med 2023; 12:6657. [PMID: 37892795 PMCID: PMC10607625 DOI: 10.3390/jcm12206657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 10/14/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune multisystem inflammatory disease in which lung involvement is the most common extra-articular manifestation. Parenchymal lung involvement or interstitial lung disease (ILD) is a significant cause of morbidity and mortality and there is a paucity of evidence-based guidance on how to best treat RA-ILD. This review article aims to evaluate the evidence from cohort studies and best real word data from registries. Extensive discussion of the relative merits and drawbacks of glucocorticoids, various biologics, small molecules and anti-fibrotics is presented. The limited available guidelines in RA-ILD are also discussed and a rational treatment algorithm is offered.
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14
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Miyata H, Sonomoto K, Fukuyo S, Nakayamada S, Nakano K, Iwata S, Miyazaki Y, Kawabe A, Aoki T, Tanaka Y. Computed tomography for malignancy screening in patients with rheumatoid arthritis before initiation of disease modifying antirheumatic drug. Rheumatology (Oxford) 2023; 62:3339-3349. [PMID: 36782362 DOI: 10.1093/rheumatology/kead075] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 01/14/2023] [Accepted: 02/01/2023] [Indexed: 02/15/2023] Open
Abstract
OBJECTIVES This study aimed to clarify the usefulness of screening for malignancies using CT before the initiation of biologic and targeted synthetic DMARDs (b/tsDMARDs) in patients with active RA. METHODS We examined 2192 patients with RA who underwent plain CT scans prior to the initiation of b/tsDMARDs. The sensitivity for detecting malignancy was measured and compared with that of regular screening (physical examination and X-ray). We then evaluated the clinical characteristics, prognosis and treatment of patients with RA with concomitant malignancies. Additionally, we determined the incidence rate of malignancy in patients with RA who were initiated on b/tsDMARDs after CT screening. RESULTS Of the 2192 patients, 33 (1.5%) were diagnosed with malignancy after CT screening. Whereas regular screening detected only seven malignancies, CT screening further detected 26 (including 19 at the early stage). On the other hand, 86% of the malignancies detectable by regular screening were at an advanced stage. Patients diagnosed with early-stage malignancies received RA treatments that included b/tsDMARDs after curative resection; 80% of these patients achieved low disease activity after 1 year. This rate was comparable to the patients without malignancy detection after screening (70%). The 5 year incidence of malignancy after the initiation of b/tsDMARDs after CT screening was lower than that of the RA cohort without CT screening (standardized incidence ratio: 0.35). CONCLUSION Screening in patients with RA using CT before the initiation of b/tsDMARDs allows for the early detection and treatment of malignancy, resulting in safer and more stable b/tsDMARD treatments.
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Affiliation(s)
- Hiroko Miyata
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
| | - Koshiro Sonomoto
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
- Department of Clinical Nursing, School of Health Sciences, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
| | - Shunsuke Fukuyo
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
- Department of Rheumatology, Wakamatsu Hospital of the University of the Occupational and Environmental Health, Japan, Kitakyushu, Japan
| | - Shingo Nakayamada
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
| | - Kazuhisa Nakano
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
- Department of Rheumatology, Kawasaki Medical School, Okayama, Japan
| | - Shigeru Iwata
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
- Department of Rheumatology, Wakayama Medical University, Wakayama, Japan
| | - Yusuke Miyazaki
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
| | - Akio Kawabe
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
| | - Takatoshi Aoki
- Department of Radiology, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
| | - Yoshiya Tanaka
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
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15
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Takeuchi T, Nishikawa K, Yamada F, Morita A, Ohtsuki M, Suzuki Y, Watanabe M, Yamanaka H, Hibi T. Real-World Safety and Efficacy of Biosimilar CT-P13 in Patients with Immune-Mediated Inflammatory Diseases: Integrated Analysis of Three Japanese Prospective Observational Studies. Drug Saf 2023; 46:991-1005. [PMID: 37700154 PMCID: PMC10584739 DOI: 10.1007/s40264-023-01340-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/26/2023] [Indexed: 09/14/2023]
Abstract
INTRODUCTION Biosimilar CT-P13 was approved with limited data from clinical trials compared to the originator infliximab in biologic-naïve patients with rheumatoid arthritis. Three prospective post-marketing surveillance studies have been conducted in Japanese biologic-naïve patients and switched patients from biologics including the originator infliximab. OBJECTIVE We performed an integrated analysis of final data from three post-marketing studies to provide long-term safety and efficacy data of CT-P13 in a real-world clinical setting. METHODS A total of 1816 patients consisting of 987 patients with rheumatoid arthritis, 342 patients with Crohn's disease, 322 patients with ulcerative colitis, and 165 patients with psoriasis were evaluated for safety. Efficacy was assessed in 1150 patients whose disease parameter values were serially collected. RESULTS Adverse drug reactions were reported in 24.2% of all patients. The incidence of adverse drug reactions differed by the prior treatment status with biologics: 30.5% in patients naïve to biologics, 17.0% in patients switched from the originator infliximab, and 33.5% in patients switched from other biologics. Infusion reactions were the most frequent adverse drug reactions (8.2%), and its incidence was significantly higher in patients with ulcerative colitis and an allergy history in a multivariable Cox regression analysis. Infection was the second most frequent (6.1%), but tuberculosis only occurred in four patients (0.2%). The incidence of infection was low in patients with Crohn's disease and psoriasis, and significant risk factors were an allergy history, comorbidities, and concomitant steroid use. Interstitial lung disease occurred in 16 patients (0.9%), including 11 patients with rheumatoid arthritis. With CT-P13 therapy, disease activity parameters decreased similarly in all four diseases, although long-term drug discontinuation rates because of inefficacy varied by disease. In naïve patients, the disease activity parameters decreased rapidly and the proportion of patients in remission increased. Patients switched from infliximab maintained lowered parameter levels with infliximab pretreatment. Decreases were also observed in patients switched from other biologics, but discontinuations were most often because of insufficient efficacy. CONCLUSIONS The integrated analysis of a large number of patients detected no new safety signals with long-term CT-P13 treatment. Efficacy in rheumatoid arthritis, psoriasis, Crohn's disease, and ulcerative colitis cases was confirmed in biologic-naïve patients and switched patients from the originator infliximab or other biologics.
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Affiliation(s)
- Tsutomu Takeuchi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Kiyohiro Nishikawa
- Quality and Pharmacovigilance Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., 2-1-1 Marunouchi, Chiyoda-ku, Tokyo, 100-0005, Japan.
- Asajes Ventures, 3-11-5 Nihonbashi Honcho, Chuo-ku, Tokyo, 103-0023, Japan.
| | - Fumika Yamada
- Quality and Pharmacovigilance Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., 2-1-1 Marunouchi, Chiyoda-ku, Tokyo, 100-0005, Japan
| | - Akimichi Morita
- Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
| | - Mamitaro Ohtsuki
- Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, 329-0498, Japan
| | - Yasuo Suzuki
- Ginza Central Clinic, 1-15-4 Ginza, Chuo-ku, Tokyo, 104-0061, Japan
| | - Mamoru Watanabe
- Advanced Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Hisashi Yamanaka
- Rheumatology Department, Sanno Medical Center, 8-5-35 Akasaka, Minato-ku, Tokyo, 107-0052, Japan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan
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16
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Tanaka Y. Making a prescribing choice for rheumatoid arthritis: a focus on small molecule drugs vs. biologics for the most favourable patient outcome. Expert Opin Pharmacother 2023; 24:1791-1798. [PMID: 37563102 DOI: 10.1080/14656566.2023.2247325] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 08/07/2023] [Accepted: 08/09/2023] [Indexed: 08/12/2023]
Abstract
INTRODUCTION The molecular targeted therapies available for rheumatoid arthritis include 10 types of biological disease-modifying antirheumatic drugs (bDMARDs) and five types of Janus kinase (JAK) inhibitors. This article reviews the differential and proper use of bDMARDs and JAK inhibitors, focusing on their efficacy and safety, based mainly on phase III clinical trials. AREA COVERED The JAK inhibitors approved for treating rheumatoid arthritis are compared with bDMARDs based on the evidence derived from global phase III trials. EXPERT OPINION In patients with inadequate responses to bDMARDs and JAK inhibitors, switching between these drugs is comparable in efficacy in both directions. Head-to-head comparison demonstrated that baricitinib and upadacitinib are more efficacious than tumor necrosis factor (TNF) inhibitors. However, the ORAL Surveillance study demonstrated that JAK inhibitors are associated with higher incidences of death, major adverse cardiovascular events, malignancies and thrombosis than TNF inhibitors in at-risk patients. The need for risk assessment by pre-treatment screening, regular monitoring during treatment, and appropriate systemic management in adverse events should be recognized. Meanwhile, some JAK-inhibitors were efficacious even for difficult-to-treat disease. These results suggest the need for establishing therapeutic strategies considering the balance between safety and efficacy in individual patients.
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Affiliation(s)
- Yoshiya Tanaka
- University of Occupational and Environmental Health Japan, Kitakyushu, Japan
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17
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Tanaka Y, Kawanishi M, Nakanishi M, Yamasaki H, Takeuchi T. Efficacy and safety of the anti-TNF multivalent NANOBODY® compound ozoralizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: A 52-week result of a Phase II/III study (OHZORA trial). Mod Rheumatol 2023; 33:883-890. [PMID: 36197757 DOI: 10.1093/mr/roac119] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 09/19/2022] [Accepted: 09/23/2022] [Indexed: 11/13/2022]
Abstract
OBJECTIVE To assess the efficacy and safety through a 52-week treatment with subcutaneous ozoralizumab at 30 or 80 mg in patients with active rheumatoid arthritis despite methotrexate therapy. METHODS This multicentre, randomized, placebo-controlled, double-blind, parallel-group confirmatory trial included a 24-week double-blind treatment period followed by a 28-week open-label treatment period. The double-blind treatment period randomized 381 (2:2:1) patients to placebo and ozoralizumab at 30 or 80 mg, and patients receiving placebo were re-randomized (1:1) to ozoralizumab at 30 or 80 mg in the open-label period. RESULTS The ozoralizumab groups showed good clinical improvement, with high American College of Rheumatology response rates at 52 weeks, as well as good improvements in other endpoints, which were observed from Day 3 and maintained through Week 52. Furthermore, the ozoralizumab groups showed a high remission rate in clinical and functional remission at Week 52. Serious adverse events occurred in a total of 23 patients in the ozoralizumab groups, without differences in incidence between doses. CONCLUSIONS Ozoralizumab demonstrated significant therapeutic effects and efficacy, which was maintained for 52 weeks. The safety profile was consistent with the evaluated results in interim analysis at Week 24, and ozoralizumab was well-tolerated up to Week 52.
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Affiliation(s)
- Yoshiya Tanaka
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | | | - Megumi Nakanishi
- Development Headquarters, Taisho Pharmaceutical Co., Ltd., Tokyo, Japan
| | - Hironori Yamasaki
- Development Headquarters, Taisho Pharmaceutical Co., Ltd., Tokyo, Japan
| | - Tsutomu Takeuchi
- Keio University School of Medicine, Tokyo, Japan
- Saitama Medical University, Saitama, Japan
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18
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Terabe K, Takahashi N, Asai S, Hirano Y, Kanayama Y, Yabe Y, Oguchi T, Fujibayashi T, Ishikawa H, Hanabayashi M, Hattori Y, Suzuki M, Kishimoto K, Ohashi Y, Imaizumi T, Imagama S, Kojima T. Reasons and risk factors for discontinuation of treatment with any biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: A long-term observational study. Mod Rheumatol 2023; 33:891-898. [PMID: 35975317 DOI: 10.1093/mr/roac090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 07/18/2022] [Accepted: 08/04/2022] [Indexed: 11/12/2022]
Abstract
OBJECTIVES Patients with rheumatoid arthritis (RA) usually switch to a second biological disease-modifying antirheumatic drugs (bDMARDs) when the first has proven to be ineffective, although some may discontinue bDMARDs treatment altogether. We investigated the total rate of bDMARDs retention and the risk of bDMARDs discontinuation in patients with RA. METHODS The study included 564 patients with RA who started bDMARDs treatment before 2008 (<65 years old, n = 413; ≥65, n = 151). The primary outcome was the incidence of bDMARDs discontinuation due to adverse events (AEs). Risk factors were examined using Fine and Gray regression models. RESULTS Among 564 patients, 74 had discontinued bDMARDs treatment due to AEs. Male sex and Steinbrocker class 3-4 were more frequent, while rheumatoid factor and concomitant methotrexate treatment were less frequent, in those aged ≥65 years than in those aged <65 years, respectively. The subdistribution hazard ratio for discontinuation was significantly higher in the ≥65 group than in the <65 years group (hazard ratio = 3.53, 95% confidence interval = 2.07-6.03). Lack of concomitant treatment with MTX was risk factor for discontinuation in patients ≥65 years. Advanced Steinbrocker class was a risk factor in patients <65 years. CONCLUSIONS Older patients are at higher risk of discontinuing bDMARDs treatment due to AEs than younger patients.
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Affiliation(s)
- Kenya Terabe
- Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Nobunori Takahashi
- Department of Orthopedic Surgery, Aichi Medical University, Nagakute, Japan
| | - Shuji Asai
- Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuji Hirano
- Department of Rheumatology, Toyohashi Municipal Hospital, Toyohashi, Japan
| | - Yasuhide Kanayama
- Department of Orthopedic Surgery, Toyota Kosei Hospital, Toyota, Japan
| | - Yuichiro Yabe
- Department of Rheumatology, Tokyo Shinjuku Medical Center, Tokyo, Japan
| | - Takeshi Oguchi
- Department of Orthopedic Surgery, Anjo Kosei Hospital, Anjo, Japan
| | | | - Hisato Ishikawa
- Department of Orthopedic Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan
| | - Masahiro Hanabayashi
- Department of Orthopedic Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan
| | - Yosuke Hattori
- Department of Orthopedic Surgery, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
| | - Mochihito Suzuki
- Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenji Kishimoto
- Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshifumi Ohashi
- Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takahiro Imaizumi
- Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan
| | - Shiro Imagama
- Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toshihisa Kojima
- Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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19
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Andronache IT, Şuţa VC, Şuţa M, Ciocodei SL, Vladareanu L, Nicoara AD, Arghir OC. Better Safe than Sorry: Rheumatoid Arthritis, Interstitial Lung Disease, and Medication-A Narrative Review. Biomedicines 2023; 11:1755. [PMID: 37371850 DOI: 10.3390/biomedicines11061755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/12/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023] Open
Abstract
It is well known that rheumatoid arthritis (RA) patients are at an increased risk of developing non-infectious pulmonary complications, especially interstitial lung disease (ILD); however, the clinician must keep in mind that lung disease could not only be a manifestation of the underlying condition, but also a consequence of using disease-modifying therapies. New-onset ILD or ILD worsening has also been reported as a possible consequence of both conventional disease-modifying antirheumatic drugs (DMARDs) and biologic agents. This study is a narrative review of the current literature regarding the potential risk of developing interstitial lung disease along with the administration of specific drugs used in controlling rheumatoid arthritis. Its purpose is to fill knowledge gaps related to this challenging patient cohort by addressing various aspects of the disease, including prevalence, disease features, treatment strategies, and patient outcomes.
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Affiliation(s)
- Iulia-Tania Andronache
- Doctoral School of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
- Department of Rheumatology, Internal Medicine Clinic, "Dr. Alexandru Gafencu" Military Emergency Hospital Constanta, 900527 Constanta, Romania
| | - Victoria-Cristina Şuţa
- 3rd Department-1st Clinical Medical Disciplines, Faculty of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
| | - Maria Şuţa
- Doctoral School of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
| | - Sabina-Livia Ciocodei
- Doctoral School of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
| | - Liliana Vladareanu
- Doctoral School of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
| | - Alina Doina Nicoara
- 3rd Department-1st Clinical Medical Disciplines, Faculty of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
| | - Oana Cristina Arghir
- Doctoral School of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
- 4th Department-2nd Clinical Medical Disciplines, Faculty of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
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20
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Shiba H, Kotani T, Nagai K, Hata K, Yamamoto W, Yoshikawa A, Wada Y, Hiramatsu Y, Makino H, Ueda Y, Onishi A, Murata K, Amuro H, Son Y, Hara R, Hirano T, Ebina K, Katayama M, Hashimoto M, Takeuchi T. Prognostic Factors Affecting Death in Patients with Rheumatoid Arthritis Complicated by Pneumocystis jirovecii Pneumonia and One-Year Clinical Course: The ANSWER Cohort Study. Int J Mol Sci 2023; 24:ijms24087399. [PMID: 37108561 PMCID: PMC10138913 DOI: 10.3390/ijms24087399] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/11/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
This multicenter retrospective study aimed to clarify the prognostic factors for mortality and changes in treatment modalities and disease activities after the onset of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA). Data regarding the clinical background, treatment modalities, and disease activity indicators of RA at the onset of PCP (baseline), and 6 months and 12 months after treatment were extracted. Of the 37 patients with RA-PCP (median age, 69 years; 73% female), chemical prophylaxis was administered to 8.1%. Six patients died during PCP treatment. The serum C-reactive protein (CRP) levels and the prednisolone (PDN) dose at baseline in the PCP death group were significantly higher than those in the survivor group. Multivariate analysis using a Cox regression model showed that PDN dose at baseline was a predictor of death from PCP in patients with RA. During the 12 months from baseline, the RA disease activity significantly decreased. A high dose of corticosteroids for RA may result in a poor prognosis when PCP is complicated. In the future, preventive administration techniques must be established for patients with RA who need PCP prevention.
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Affiliation(s)
- Hideyuki Shiba
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan
| | - Takuya Kotani
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan
| | - Koji Nagai
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan
| | - Kenichiro Hata
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan
| | - Wataru Yamamoto
- Department of Health Information Management, Kurashiki Sweet Hospital, Okayama 710-0016, Japan
| | - Ayaka Yoshikawa
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan
| | - Yumiko Wada
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan
| | - Yuri Hiramatsu
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan
| | - Hidehiko Makino
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan
| | - Yo Ueda
- Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Akira Onishi
- Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8303, Japan
| | - Koichi Murata
- Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8303, Japan
| | - Hideki Amuro
- First Department of Internal Medicine, Kansai Medical University, Osaka 573-1191, Japan
| | - Yonsu Son
- First Department of Internal Medicine, Kansai Medical University, Osaka 573-1191, Japan
| | - Ryota Hara
- Rheumatology Clinic and Department of Orthopaedic Surgery, Nara Medical University, Nara 634-8521, Japan
| | - Toru Hirano
- Department of Rheumatology, Nishinomiya Municipal Central Hospital, Nishinomiya 663-8014, Japan
| | - Kosuke Ebina
- Department of Musculoskeletal Regenerative Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
| | - Masaki Katayama
- Department of Rheumatology, Osaka Red Cross Hospital, Osaka 543-0027, Japan
| | - Motomu Hashimoto
- Department of Clinical Immunology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan
| | - Tohru Takeuchi
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan
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21
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Nunokawa T, Chinen N, Shimada K, Kimura M, Tateishi M, Chen FY, Setoguchi K, Sugihara M. Efficacy of sulfasalazine for the prevention of Pneumocystis pneumonia in patients with rheumatoid arthritis: A multicentric self-controlled case series study. J Infect Chemother 2023; 29:193-197. [PMID: 36334836 DOI: 10.1016/j.jiac.2022.10.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/24/2022] [Accepted: 10/30/2022] [Indexed: 11/11/2022]
Abstract
INTRODUCTION Pneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that sulfasalazine enhances Pneumocystis clearance from the lung by accelerating macrophage activity. METHODS The self-controlled case series (SCCS) method was used to investigate the association between sulfasalazine use and PCP development in patients with RA without the effect of time-invariant, interpatient confounders. PCP episodes which developed in patients with RA at five hospitals between 2003 and 2019 were identified. PCP was defined by the following criteria: 1) detection of Pneumocystis jirovecii in respiratory specimens by polymerase chain reaction; 2) clinical symptoms (pyrexia, dry cough, dyspnea or hypoxia); 3) diffuse interstitial infiltrate on chest imaging; and 4) absence of PCP prophylaxis. The PCP incidence rate ratio (IRR) was compared between periods with and without sulfasalazine use by conditional Poisson regression. RESULTS Fifty episodes of PCP were identified in 49 patients. Thirty patients received sulfasalazine at some point during their observation. While 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use, only one episode of PCP developed in 103.7 person-years with sulfasalazine use. Sulfasalazine use was associated with a decreased PCP risk (adjusted IRR <0.01; 95% confidence interval <0.01-0.03) after adjusting for age and glucocorticoid, methotrexate, and tumor necrosis factor inhibitor administration. CONCLUSION Our study demonstrated a preventive effect of sulfasalazine against PCP in patients with RA.
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Affiliation(s)
- Takahiro Nunokawa
- Department of Rheumatic Diseases, Tama-Namub Chiiki Hosipital, 2-1-2, Nakazawa, Tama-shi, Tokyo, Japan; Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai, Fuchu-shi, Tokyo, Japan.
| | - Naofumi Chinen
- Department of Rheumatic Diseases, Tama-Namub Chiiki Hosipital, 2-1-2, Nakazawa, Tama-shi, Tokyo, Japan.
| | - Kota Shimada
- Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai, Fuchu-shi, Tokyo, Japan.
| | - Makiko Kimura
- Department of Rheumatology, Tokyo Metropolitan Ohtsuka Hospital, 2-8-1, Minamiohtsuka, Toshima-ku, Tokyo, Japan.
| | - Mutsuto Tateishi
- Department of Rheumatology, Tokyo Metropolitan Ohtsuka Hospital, 2-8-1, Minamiohtsuka, Toshima-ku, Tokyo, Japan.
| | - Fang Yi Chen
- Department of Rheumatology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, Japan.
| | - Keigo Setoguchi
- Department of Rheumatology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, Japan.
| | - Makoto Sugihara
- Department of Rheumatic Diseases, Tama-Hokubu Medical Center, 1-7-1 Aoba-cho, Higashimurayama-shi, Tokyo, Japan.
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22
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Jahnich N, Arkwright PD. Regional risk of tuberculosis and viral hepatitis with tumor necrosis factor-alpha inhibitor treatment: A systematic review. Front Pharmacol 2023; 14:1046306. [PMID: 36744250 PMCID: PMC9894886 DOI: 10.3389/fphar.2023.1046306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 01/05/2023] [Indexed: 01/21/2023] Open
Abstract
Background: TNFα inhibitors are regularly used to treat autoimmune diseases. Tuberculosis (TB) and viral hepatitis B are considered potential infectious complications, and screening and surveillance are therefore recommended. Current guidelines do not take into account regional differences in endemicity of these infections. Methods: A systematic literature review of TB and viral hepatitis in patients receiving TNFα-inhibitors was performed, searching in PubMed, Embase, MEDLINE and Web of Science databases. Studies were selected against predefined eligibility criteria and assessed using the Newcastle-Ottawa scale. The number of TB and viral hepatitis cases/1,000 TNFα-inhibitor patients were evaluated, and regional variation compared. Results: 105 observational studies involving over 140,000 patients were included. Overall, 1% of patients developed TB or viral hepatitis B. TB cases/1,000 TNFα-inhibitor patients were 4-fold higher in Asia, Africa, and South America than in Europe, North America, and Australasia where only 0%-0.4% of patients developed TB. Hepatitis B cases/1,000 patients were over 15-fold higher in countries with high prevalence (China, Taiwan, South Korea, Thailand) compared with low prevalence (p < 0.00001) where only 0.4% of patients developed hepatitis B. Only three of 143 patients developed viral hepatitis C, and there was insufficient data to allow regional sub-analysis. Conclusion: TB and viral hepatitis B infections in patients treated with TNFα inhibitors are largely confined to countries with high prevalence of these infections. As only 1/2,500 patients in low prevalence countries treated with TNFα inhibitors develop TB or viral hepatitis B, we suggest an individualized, risk-based approach, rather than universal screening for all patients.
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Affiliation(s)
| | - Peter D. Arkwright
- Lydia Becker Institute of Immunology and Inflammation, Manchester Incubator Building, University of Manchester, Manchester, United Kingdom
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23
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Itagaki M, Iketani O, Enoki Y, Chuang VTG, Taguchi K, Uno S, Uchida S, Namkoong H, Uwamino Y, Takano Y, Hasegawa N, Matsumoto K. Analysis of Risk Factors for Developing Tuberculosis in Patients Who Received Prophylactic Latent Tuberculosis Infection Treatment with Experience of Biologic Medications. Biol Pharm Bull 2023; 46:1832-1837. [PMID: 38044103 DOI: 10.1248/bpb.b23-00521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
Biologic medications have dramatically improved the treatment outcomes of immunological inflammatory diseases, but their immunosuppressive effects put patients at risk for tuberculosis (TB). We investigated the risk factors for developing TB in patients treated for latent tuberculosis infection (LTBI) who also had experience of using biologic medications. At Keio University Hospital, we retrospectively investigated patients treated with anti-mycobacterial drugs before or concurrently with biologic medications from January 2012 to August 2020. Patients in the 'follow-on cases group' who had a positive TB screening test after initiating biologic medications and subsequently started LTBI treatment were excluded. We researched and compared the patient characteristics for TB and non-TB patient groups. Of the 146 eligible patients, 5 (3.4%) developed TB. The incidence rate was 600/100000 person-years. There were no significant differences between TB and non-TB patient groups in the history of TB, interferon-gamma release assay (IGRA), duration of biologic medication therapy, LTBI treatment periods, concomitant use of calcineurin inhibitors or anti-rheumatic drugs. The percentage of patients who received prednisolone at a dose of ≥15 mg for more than 1 month was higher in those who developed TB than in those who did not (40.0 vs. 7.1%, p = 0.054); however, this difference was not statistically significant. Regular monitoring of TB is necessary for long-term concomitant use of high prednisolone doses during and after the administration of biologic medications.
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Affiliation(s)
- Marina Itagaki
- Division of Pharmacodynamics, Faculty of Pharmacy, Keio University
| | - Osamu Iketani
- Department of Infectious Diseases, Keio University School of Medicine
| | - Yuki Enoki
- Division of Pharmacodynamics, Faculty of Pharmacy, Keio University
| | - Victor Tuan Giam Chuang
- Discipline of Pharmacy, Curtin Medical School, Faculty of Health Sciences, Curtin University
| | - Kazuaki Taguchi
- Division of Pharmacodynamics, Faculty of Pharmacy, Keio University
| | - Shunsuke Uno
- Department of Infectious Diseases, Keio University School of Medicine
| | - Sho Uchida
- Department of Infectious Diseases, Keio University School of Medicine
| | - Ho Namkoong
- Department of Infectious Diseases, Keio University School of Medicine
| | - Yoshifumi Uwamino
- Department of Infectious Diseases, Keio University School of Medicine
| | - Yaoko Takano
- Department of Infectious Diseases, Keio University School of Medicine
| | - Naoki Hasegawa
- Department of Infectious Diseases, Keio University School of Medicine
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24
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Tanaka Y. What are the hot topics in Japanese rheumatology? Go above and beyond. RMD Open 2023; 9:e002819. [PMID: 36717187 PMCID: PMC9887709 DOI: 10.1136/rmdopen-2022-002819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 01/02/2023] [Indexed: 01/31/2023] Open
Abstract
Japanese rheumatology and immunology have contributed to progress in the field and advancement of rheumatology, including postmarketing surveillance, development of IL-6-targeting therapy and concept of drug tapering, have accelerated in the 21st century. The 67th Annual Scientific Meeting of the Japan College of Rheumatology, held on Fukuoka on 24 April 2023-26 April 2023, will go ahead and beyond such an advancement. Profound discussion on future perspectives such as precision medicine, the elucidation of pathology and genome-based drug discovery by multilayered integration with various types of omics information, information on metabolome and proteome of blood metabolites, and database of target proteins and compounds for drug discovery will be discussed.
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Affiliation(s)
- Yoshiya Tanaka
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Fukuoka, Japan
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25
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Miyazaki S, Fujita K, Ozaki S, Ichiyama S, Ito M, Hoashi T, Kanda N, Saeki H. Active Tuberculosis in a Patient Receiving Adalimumab for Psoriatic Arthritis and Chemoprophylaxis for Latent Tuberculosis Infection. J NIPPON MED SCH 2023; 90:480-485. [PMID: 38246618 DOI: 10.1272/jnms.jnms.2023_90-610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
Tumor necrosis factor (TNF) inhibitors, including adalimumab, are widely used to treat refractory psoriatic arthritis (PsA). Although isoniazid chemoprophylaxis is generally effective in preventing reactivation of latent tuberculosis infection (LTBI), prophylactic measures do not fully protect against development of active tuberculosis. We report a rare case of active tuberculosis despite chemoprophylaxis for LTBI in a patient receiving adalimumab for PsA. A 60-year-old Japanese woman who had received a diagnosis of psoriasis at age 35 years presented with arthralgia of the right hand, which she first noticed 2 months previously. Physical examination showed scattered erythematous papules and plaques with scales on her trunk, extremities, and scalp. Her right metacarpophalangeal and proximal interphalangeal joints were swollen and painful, and her right wrist and elbow were painful. PsA was diagnosed and adalimumab was initiated. Because an interferon-γ release assay (IGRA) showed a borderline result at screening, isoniazid was administered as chemoprophylaxis for LTBI. At 22 months after initiation of adalimumab, IGRA was positive and chest CT disclosed centrilobular nodules in both lungs and swelling of multiple lymph nodes. Culture of sputum at 24 months demonstrated Mycobacterium tuberculosis. Active tuberculosis was diagnosed, and treatment with a combination of isoniazid, rifampicin, ethambutol hydrochloride, and pyrazinamide was started. To ensure timely diagnosis and treatment of active tuberculosis, a tuberculosis expert should be consulted at an early stage, with regular screening and monitoring.
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Affiliation(s)
| | - Kazue Fujita
- Department of Pulmonary Medicine and Oncology, Nippon Medical School
| | - Saeko Ozaki
- Department of Dermatology, Nippon Medical School
| | | | - Michiko Ito
- Department of Dermatology, Nippon Medical School
| | | | - Naoko Kanda
- Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital
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26
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Deng C, Zhao X, Chen Y, Ai K, Zhang Y, Gong T, Zeng C, Lei G. Engineered Platelet Microparticle-Membrane Camouflaged Nanoparticles for Targeting the Golgi Apparatus of Synovial Fibroblasts to Attenuate Rheumatoid Arthritis. ACS NANO 2022; 16:18430-18447. [PMID: 36342327 DOI: 10.1021/acsnano.2c06584] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Synovial fibroblasts in rheumatoid arthritis (RA) joints mediate synovial hyperplasia, progressive joint destruction, and the potential spread of disease between joints by producing multiple pathogenic proteins. Here, we deliver all-trans retinoic acid (ATRA) to selectively down-regulate these pathogenic factors, with a Golgi-targeting platelet microparticle-mimetic nanoplatform (termed Gol-PMMNP) which comprises a nanoparticle core and a platelet microparticle membrane coating labeled with a Golgi apparatus-targeting peptide. Gol-PMMNPs are shown to target synovial fibroblasts derived from RA patients via integrin α2β1-mediated endocytosis and accumulate in the Golgi apparatus by retrograde transport. ATRA-loaded Gol-PMMNPs (ATRA-Gol-PMMNPs) cause structural disruption of the Golgi apparatus, leading to an efficient reduction of pathogenic protein secretion in RA synovial fibroblasts. In rats with collagen-induced arthritis, Gol-PMMNPs display an arthritic joint-specific distribution, and ATRA-Gol-PMMNPs effectively reduce concentrations of pathogenic factors therein, including inflammatory cytokines, chemokines, and matrix-degrading enzymes within these joints. Additionally, ATRA-Gol-PMMNP treatment results in inflammatory remission and decreased bone erosion in both arthritic and proximal joints. Furthermore, ATRA-Gol-PMMNPs induce negligible toxicity to major organs. Taken together, ATRA-Gol-PMMNPs inhibit the progression of RA through reducing the production of multiple pathogenic mediators by synovial fibroblasts.
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Affiliation(s)
- Caifeng Deng
- Department of Orthopaedics and Hunan Key Laboratory of Joint Degeneration and Injury, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Xuan Zhao
- Department of Orthopaedics and Hunan Key Laboratory of Joint Degeneration and Injury, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Yuxiao Chen
- Department of Orthopaedics and Hunan Key Laboratory of Joint Degeneration and Injury, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Kelong Ai
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
| | - Yuqing Zhang
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, United States
- The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, United States
| | - Tao Gong
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610064, China
| | - Chao Zeng
- Department of Orthopaedics and Hunan Key Laboratory of Joint Degeneration and Injury, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Guanghua Lei
- Department of Orthopaedics and Hunan Key Laboratory of Joint Degeneration and Injury, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
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27
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Takeuchi T, Kawanishi M, Nakanishi M, Yamasaki H, Tanaka Y. Phase II/III Results of a Trial of Anti-Tumor Necrosis Factor Multivalent NANOBODY Compound Ozoralizumab in Patients With Rheumatoid Arthritis. Arthritis Rheumatol 2022; 74:1776-1785. [PMID: 35729713 PMCID: PMC9828347 DOI: 10.1002/art.42273] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 05/27/2022] [Accepted: 06/10/2022] [Indexed: 01/12/2023]
Abstract
OBJECTIVE To assess the efficacy and safety of subcutaneous administration of 30 mg or 80 mg of ozoralizumab plus methotrexate (MTX) in patients with rheumatoid arthritis (RA) whose disease remained active despite MTX therapy. METHODS In this multicenter, double-blind, parallel-group, placebo-controlled phase II/III trial, 381 patients were randomized to receive placebo, ozoralizumab 30 mg, or ozoralizumab 80 mg, plus MTX subcutaneously injected every 4 weeks for 24 weeks. The primary end points were the response rates based on the American College of Rheumatology 20% improvement criteria (ACR20) at week 16 and change in the Sharp/van der Heijde score (ΔSHS) from baseline to week 24. RESULTS The proportion of patients with an ACR20 response at week 16 was significantly higher (P < 0.001) in both ozoralizumab groups (79.6% for 30 mg, 75.3% for 80 mg), compared with placebo (37.3%); these improvements were observed from the first week of treatment. The proportion of the patients with structural nonprogression (ΔSHS ≤0) was significantly higher in both ozoralizumab groups than in the placebo group. For some secondary end points, significantly greater improvements were observed starting from as early as day 3. Serious adverse events occurred in 4 patients in the ozoralizumab 30-mg group and 5 patients in the ozoralizumab 80-mg group. CONCLUSION In patients with active RA who received ozoralizumab in combination with MTX, the signs and symptoms of RA were significantly reduced as compared with the outcomes in those receiving placebo. Ozoralizumab demonstrated acceptable tolerability with no new safety signals when compared with other antibodies against tumor necrosis factor.
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Affiliation(s)
- Tsutomu Takeuchi
- Keio University School of Medicine, Tokyo, and Saitama Medical UniversitySaitamaJapan
| | | | | | | | - Yoshiya Tanaka
- University of Occupational and Environmental Health JapanKitakyushuJapan
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28
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Sierra CM, Daiya KC. Prophylaxis for Pneumocystis jirovecii pneumonia in patients with inflammatory bowel disease: A systematic review. Pharmacotherapy 2022; 42:858-867. [PMID: 36222368 PMCID: PMC9828113 DOI: 10.1002/phar.2733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 09/26/2022] [Accepted: 09/29/2022] [Indexed: 11/07/2022]
Abstract
Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications utilized for the treatment of IBD affect the immune system, potentially further increasing the risk of PJP. Recommendations for prophylaxis against PJP in this patient population are based upon limited evidence, and risk factors for PJP development are not well-agreed upon. The purpose of this systematic review was to consolidate and evaluate the evidence for PJP prophylaxis in patients with IBD. An electronic literature search was performed, and 29 studies were included in the review, of which 24 were case reports or case series. Combined data from five cohort studies showed an absolute risk of developing PJP to be 0.07%. The majority of patients who developed PJP were receiving corticosteroids at the time of diagnosis (76%). The number of concomitant immunosuppressants received at time of PJP diagnosis varied from one to four. All studies reporting treatment of PJP utilized sulfamethoxazole-trimethoprim. Of the 27 studies reporting mortality data, 19% of patients died. Given the lack of conclusive data regarding risk factors for PJP development and the overall low incidence of PJP in patients with IBD, it is recommended to assess the patient's risk on a case-by-case basis to determine whether PJP prophylaxis is warranted.
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29
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Takagi M, Atsumi T, Matsuno H, Tamura N, Fujii T, Okamoto N, Takahashi N, Nakajima A, Nakajima A, Tsujimoto N, Nishikawa A, Ishii T, Takeuchi T, Kuwana M. Safety and Effectiveness of Baricitinib for Rheumatoid Arthritis in Japanese Clinical Practice: 24-Week Results of All-Case Post-Marketing Surveillance. Mod Rheumatol 2022:6657693. [PMID: 35932218 DOI: 10.1093/mr/roac089] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 07/27/2022] [Accepted: 08/06/2022] [Indexed: 11/14/2022]
Abstract
OBJECTIVES To assess safety and effectiveness of baricitinib treatment for rheumatoid arthritis (RA) in real-world clinical practice. METHODS This ongoing all-case post-marketing surveillance study (starting September 2017) includes all patients with RA treated with baricitinib in Japan. Safety and effectiveness (disease activity) were assessed for 24 weeks. RESULTS Safety analyses to February 2021 included 4731 patients (initial baricitinib dose: 4 mg/day, n=3058; 2 mg/day, n=1661; other, n=12); 1059 (22.38%) were ≥75 years, and 3362 (71.06%) previously received biologic therapy. Overall observational period was 1863.14 patient-years; 1174 (24.82%) patients discontinued baricitinib before Week 24, mostly for lack of effectiveness (n=478; 10.10%). Adverse events occurred in 1271 (26.87%) patients (serious: 203 [4.29%]; death: 18 [0.38%]). The incidence of herpes zoster, hepatic function disorder, and serious infection was 3.09%, 2.77%, and 1.90%, respectively. Malignancy occurred in 17 patients (0.36%) and major adverse cardiovascular events in seven patients (0.15%). Among patients with effectiveness data, at least 26.57% (Boolean) achieved remission at Week 24. CONCLUSIONS This large nationwide surveillance study evaluated the safety and effectiveness of 24 weeks of baricitinib for RA in real-world clinical practice. Continued surveillance of long-term safety is ongoing.
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Affiliation(s)
- Michiaki Takagi
- Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Tatsuya Atsumi
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | | | - Naoto Tamura
- Department of Internal Medicine and Rheumatology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Takao Fujii
- Department of Rheumatology and Clinical Immunology, Wakayama Medical University, Wakayama, Japan
| | - Nami Okamoto
- Department of Pediatrics, School of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Nobunori Takahashi
- Department of Orthopaedics/Rheumatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | | | - Ayako Nakajima
- Center for Rheumatic Diseases, Mie University Hospital, Tsu, Japan
| | | | | | | | | | - Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
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Mori S, Ueki Y, Miyamura T, Ishii K, Hidaka T, Yoshitama T, Nakamura K, Suenaga Y. Outcomes and Risk Factors for Mortality in Pneumocystis Pneumonia Patients with Rheumatoid Arthritis: A Multicenter Retrospective Cohort Study. Mod Rheumatol 2022:6654505. [PMID: 35920411 DOI: 10.1093/mr/roac088] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/20/2022] [Accepted: 08/02/2022] [Indexed: 11/13/2022]
Abstract
OBJECTIVE To evaluate outcomes and risk factors for death in patients with rheumatoid arthritis (RA) who developed Pneumocystis pneumonia (PCP). METHODS : We included RA patients who were diagnosed with PCP at seven participating community hospitals between July 2005 and October 2020. Clinical features were compared between survivors and non-survivors. Disease-modifying antirheumatic drugs (DMARDs) before PCP onset and after PCP recovery were also examined. RESULTS Seventy RA patients developed PCP, and among them, 60 (85.7%) received methotrexate (MTX) monotherapy (40%) or MTX combination therapy with other DMARDs (45.7%). PCP was more likely to occur after 12 months of MTX monotherapy and within 3 months of MTX combination therapy. Thirteen patients (18.6%) died despite PCP treatment. Multivariable logistic regression analysis revealed that coexisting RA-associated interstitial lung disease (RA-ILD; odds ratio [OR] 6.18, 95% confidence interval [CI] 1.17-32.63) and delayed PCP treatment with anti-Pneumocystis drugs (OR 15.29, 95% CI 1.50-156.15) are significant risk factors for PCP mortality in RA patients. Most survivors successfully resumed DMARD therapy without PCP prophylaxis; one recurrent PCP case was observed during follow-up (median, 4.1 years). CONCLUSION To avoid a treatment delay, RA patients should be followed-up for signs and symptoms of PCP development, especially those with RA-ILD.
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Affiliation(s)
- Shunsuke Mori
- Department of Rheumatology, Clinical Research Center for Rheumatic Disease, National Hospital Organization, Kumamoto Saishun Medical Center, Kohshi, Kumamoto, Japan
| | - Yukitaka Ueki
- Rheumatic and Collagen Disease Center, Sasebo Chuo Hospital, Sasebo, Nagasaki, Japan
| | - Tomoya Miyamura
- Department of Internal Medicine and Rheumatology, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan
| | - Koji Ishii
- Department of Rheumatology, Oita Red Cross Hospital, Oita, Japan
| | - Toshihiko Hidaka
- Institute of Rheumatology, Miyazaki Zenjinkai Hospital, Miyazaki, Japan
| | - Tamami Yoshitama
- Yoshitama Clinic for Rheumatic Diseases, Kirishima, Kagoshima, Japan
| | - Kazuyoshi Nakamura
- Department of Respiratory Medicine, National Hospital Organization Kumamoto Saishun Medical Center, Kohshi, Kumamoto, Japan
| | - Yasuo Suenaga
- Department of Rheumatology, National Hospital Organization Beppu Medical Center, Beppu, Oita, Japan
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Kameda H, Nishida K, Nanki T, Watanabe A, Oshima Y, Momohara S. Safety and Effectiveness of Certolizumab Pegol in Japanese Patients with Rheumatoid Arthritis: Results from a 24-Week Post-Marketing Surveillance Study. Mod Rheumatol 2022; 33:460-471. [PMID: 35822806 DOI: 10.1093/mr/roac073] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 06/20/2022] [Indexed: 11/13/2022]
Abstract
OBJECTIVES To report 24-week safety and effectiveness data of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis (RA) from a post-marketing surveillance study. METHODS Enrolled patients were newly receiving CZP. All adverse events (AEs) and adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes included: 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) and EULAR response. Missing data were imputed using last observation carried forward. RESULTS 3,727 patients were enrolled; safety and effectiveness were evaluated in 3,586 and 1,794 patients, respectively. 24.9% of patients reported AEs (n=893/3,586) and 14.7% reported ADRs (528/3,586). Serious AEs and serious ADRs were reported in 8.3% (298/3,586) and 5.3% (190/3,586), respectively. Selected serious ADRs of interest included infections (n=110; 3.1%), tuberculosis (6; 0.2%), interstitial pneumonia (15; 0.4%), malignancy (8; 0.2%) and hepatic function disorder (7; 0.2%). No allergic reactions, autoimmune disease, cardiac failure, demyelinating diseases or pancytopenia were reported. Mean DAS28-ESR reduced from 4.8 (baseline) to 3.4 (final evaluation). At final evaluation, 34.7% of patients achieved EULAR good response. CONCLUSIONS These real-world safety and effectiveness results were consistent with previously reported data, with no new safety signals identified. Long-term, real-world CZP safety and effectiveness data are needed.
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Affiliation(s)
- Hideto Kameda
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Toho University (Ohashi Medical Center), Tokyo, Japan
| | - Keiichiro Nishida
- Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Japan
| | - Toshihiro Nanki
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Toho University (Omori Medical Center), Tokyo, Japan
| | | | | | - Shigeki Momohara
- Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan
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Ben Mrid R, Bouchmaa N, Ainani H, El Fatimy R, Malka G, Mazini L. Anti-rheumatoid drugs advancements: New insights into the molecular treatment of rheumatoid arthritis. Biomed Pharmacother 2022; 151:113126. [PMID: 35643074 DOI: 10.1016/j.biopha.2022.113126] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/13/2022] [Accepted: 05/13/2022] [Indexed: 11/02/2022] Open
Abstract
Rheumatoid arthritis (RA) is one of more than 100 types of arthritis. This chronic autoimmune disorder affects the lining of synovial joints in about 0.5% of people and may induce severe joints deformity and disability. RA impacts health life of people from all sexes and ages with more prevalence in elderly and women people. Significant improvement has been noted in the last two decades revealing the mechanisms of the development of RA, the improvement of the early diagnosis and the development of new treatment options. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) remain the most known treatments used against RA. However, not all patients respond well to these drugs and therefore, new solutions are of immense need to improve the disease outcomes. In the present review, we discuss and highlight the recent findings concerning the different classes of RA therapies including the conventional and modern drug therapies, as well as the recent emerging options including the phyto-cannabinoid and cell- and RNA-based therapies. A better understanding of their mechanisms and pathways might help find a specific target against inflammation, cartilage damage, and reduce side effects in arthritis.
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Affiliation(s)
- Reda Ben Mrid
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
| | - Najat Bouchmaa
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
| | - Hassan Ainani
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
| | - Rachid El Fatimy
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
| | - Gabriel Malka
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
| | - Loubna Mazini
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco.
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Sonomoto K, Tanaka H, Nguyen TM, Yoshinari H, Nakano K, Nakayamada S, Tanaka Y. Prophylaxis against pneumocystis pneumonia in rheumatoid arthritis patients treated with b/tsDMARDs: insights from 3787 cases in the FIRST registry. Rheumatology (Oxford) 2022; 61:1831-1840. [PMID: 34382090 PMCID: PMC9071566 DOI: 10.1093/rheumatology/keab647] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 08/08/2021] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVES The use of biologic and targeted synthetic (b/ts) DMARDs in the treatment of RA is increasing. Therefore, prevention of b/tsDMARDs-induced infection is important. Here we describe a prophylaxis protocol for preventing pneumocystis pneumonia (PCP) in RA patients treated with b/tsDMARDs. METHODS The study subjects were 3787 RA patients from the FIRST registry. They were divided into cohort 1 (n = 807, requiring prophylaxis against PCP based on physicians' assessment at the point of new treatment with or switch to b/tsDMARDs) and cohort 2 (n = 2980, receiving strategic PCP prophylaxis). The incidence and risk factors for PCP were investigated. RESULTS Twenty-six PCP cases were observed throughout the study. After the introduction of strategic PCP prophylaxis, PCP incidence diminished from 0.51/100 person-years (PYs) to 0.21/100 PYs (risk ratio = 0.42). Sulfamethoxazole and trimethoprim in combination (SMX-TMP) showed greater efficacy in the prevention of PCP than pentamidine inhalation (P <0.0001). The prophylaxis rate increased chronologically despite the falls in the average SMX-TMP dose and in the incidence of PCP. Subanalysis of the data for 929 patients from both groups who did not receive prophylaxis showed that old age, high BMI, coexisting lung diseases, low lymphocyte count, and low serum IgG levels increased the risk of PCP development. Development of PCP could be predicted (using an equation based on these variables) in patients not treated with glucocorticoids [area under the curve (AUC) = 0.910)], but less accurately in those on glucocorticoids (AUC = 0.746). CONCLUSIONS Our study clarified the risk factors for PCP in RA patients on b/tsDMARDs treatment and highlighted and defined the criteria for effective prophylaxis against PCP.
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Affiliation(s)
- Koshiro Sonomoto
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
| | - Hiroaki Tanaka
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
| | - Tuan Manh Nguyen
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
| | - Hiroko Yoshinari
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
| | - Kazuhisa Nakano
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
- Department of Rheumatology, Kawasaki Medical School, Kurashiki, Japan
| | - Shingo Nakayamada
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
| | - Yoshiya Tanaka
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
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Takeda K, Sumi T, Nagahisa Y, Matsuura K, Sekikawa M, Watanabe H, Yamada Y, Chiba H. Refractory flare-up of severe bronchial asthma controlled with mepolizumab due to Pneumocystis pneumonia: a case report. Allergy Asthma Clin Immunol 2022; 18:35. [PMID: 35461263 PMCID: PMC9035245 DOI: 10.1186/s13223-022-00678-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 04/15/2022] [Indexed: 12/05/2022] Open
Abstract
Background Biologics dramatically improve symptoms of severe asthma; however, various exacerbating factors may induce flare-up. Pneumocystis spp. have not been reported as a cause of asthma exacerbation during biologic use, although patients with severe asthma have high levels of antibodies against Pneumocystis spp. Case presentation An 87-year-old female with severe asthma that was well-controlled with mepolizumab, who developed a steroid-resistant refractory flare-up. Chest computed tomography showed bilateral ground glass opacities, and results of polymerase chain reaction tests on induced sputum were positive for Pneumocystis DNA. Therefore, a diagnosis of Pneumocystis pneumonia was made. The clinical symptoms improved after treatment with sulfamethoxazole–trimethoprim. Conclusion Clinicians should be aware of Pneumocystis pneumonia as a cause of refractory exacerbation of bronchial asthma during use of interleukin-5 inhibitors.
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Affiliation(s)
- Kazuya Takeda
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, 38-3 Goryoukaku-Cho, Hakodate-shi, Hokkaido, 040-8611, Japan.,Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Toshiyuki Sumi
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, 38-3 Goryoukaku-Cho, Hakodate-shi, Hokkaido, 040-8611, Japan. .,Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.
| | - Yuta Nagahisa
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, 38-3 Goryoukaku-Cho, Hakodate-shi, Hokkaido, 040-8611, Japan.,Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Keigo Matsuura
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, 38-3 Goryoukaku-Cho, Hakodate-shi, Hokkaido, 040-8611, Japan.,Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Motoki Sekikawa
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, 38-3 Goryoukaku-Cho, Hakodate-shi, Hokkaido, 040-8611, Japan.,Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hiroki Watanabe
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, 38-3 Goryoukaku-Cho, Hakodate-shi, Hokkaido, 040-8611, Japan
| | - Yuichi Yamada
- Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, 38-3 Goryoukaku-Cho, Hakodate-shi, Hokkaido, 040-8611, Japan
| | - Hirofumi Chiba
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan
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Ohmura SI, Homma Y, Masui T, Miyamoto T. Factors Associated with Pneumocystis jirovecii Pneumonia in Patients with Rheumatoid Arthritis Receiving Methotrexate: A Single-center Retrospective Study. Intern Med 2022; 61:997-1006. [PMID: 34511571 PMCID: PMC9038457 DOI: 10.2169/internalmedicine.8205-21] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy. Methods This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis. Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL [hazard ratio (HR) 5.50, p=0.003], other DMARDs (HR 5.98, p=0.002), and serum albumin <3.5 mg/dL (HR 4.30, p=0.01) were risk factors for the development of PCP during MTX therapy. Patients with these risk factors had a significantly higher cumulative probability of developing PCP than patients who lacked these risk factors. Conclusion Clinicians should pay close attention to patients with RA who possess risk factors for the development of PCP during MTX therapy.
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Affiliation(s)
| | - Yoichiro Homma
- Department of General Internal Medicine, Seirei Hamamatsu General Hospital, Japan
| | - Takayuki Masui
- Department of Radiology, Seirei Hamamatsu General Hospital, Japan
| | - Toshiaki Miyamoto
- Department of Rheumatology, Seirei Hamamatsu General Hospital, Japan
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Long-Term Safety and Effectiveness of Adalimumab in Japanese Patients with Noninfectious Intermediate, Posterior, or Panuveitis: Post-Marketing Surveillance of 251 Patients. Ophthalmol Ther 2022; 11:1147-1161. [PMID: 35305254 PMCID: PMC9114192 DOI: 10.1007/s40123-022-00493-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 02/24/2022] [Indexed: 11/12/2022] Open
Abstract
Introduction The aim of this nationwide, prospective post-marketing surveillance was to assess the safety and effectiveness of up to 52 weeks of adalimumab treatment in patients with noninfectious intermediate, posterior, or panuveitis in Japanese clinical practice. Methods This post-marketing surveillance was conducted at 60 medical facilities in Japan from October 2016 to June 2020. Patients with noninfectious intermediate, posterior, or panuveitis who were administered adalimumab (Humira®, AbbVie Inc.) for the first time were eligible. Subcutaneous adalimumab was initially administered at 80 mg, followed by 40 mg 1 week later, then 40 mg every 2 weeks. Safety measures included the incidence of adverse events (AEs) and adverse drug reactions (ADRs; primary endpoint). Effectiveness measures included visual acuity, anterior chamber cell grade, vitreous haze, macular edema, foveal retinal thickness, uveitis recurrence rate, and oral corticosteroid dose. Health-related quality of life was evaluated using the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25). Results During 52 weeks of surveillance, AEs and ADRs occurred in 70 (27.9%) and 47 (18.7%) of 251 patients, respectively. The most common ADR was infection (21/251 patients; 8.4%), including serious infections in eight (3.2%) patients. ADRs were more frequent in patients ≥ 65 years of age, those with concurrent diseases, and those with past medical history. Four patients developed tuberculosis. The uveitis recurrence rate was 24.8% (61/246 patients). All effectiveness measures tended to improve from baseline to week 52, and mean corticosteroid doses decreased. Clinically meaningful changes were observed for most VFQ-25 subscales. Conclusions The safety profile of adalimumab was generally consistent with previous reports, and no new safety concerns were identified. Trial registration ClinicalTrials.gov: NCT02916017. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-022-00493-z.
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Shinagawa M, Namba K, Mizuuchi K, Iwata D, Hase K, Suzuki K, Hirooka K, Kitaichi N, Hiraoka M, Ishida S. The Steroid-Sparing Effect of Adalimumab in the Treatment for the Recurrent Phase of Vogt-Koyanagi-Harada Disease. Ocul Immunol Inflamm 2022; 31:501-505. [PMID: 35212595 DOI: 10.1080/09273948.2022.2037657] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
PURPOSE To reveal the steroid-sparing effect of adalimumab (ADA) in the treatment for the chronic recurrent phase of Vogt-Koyanagi-Harada (VKH) disease. CASES AND METHODS Thirty-six eyes from 18 cases of the recurrent phase of VKH disease treated with ADA over 12 months were examined retrospectively. Before the introduction of ADA, 4 cases received prednisolone (PSL) monotherapy and other 14 cases received PSL and cyclosporine A (CYA) combination therapy. RESULTS In cases treated with PSL and CYA, CYA was discontinued when ADA was introduced. The minimum dose of PSL to control intraocular inflammation (min dose of PSL) could be reduced in all cases after the introduction of ADA (from 16.9 ± 7.9 mg to 6.3 ± 3.1 mg). No serious adverse events were observed in the observational periods. CONCLUSION By comparing the min dose of PSL before and after the introduction of ADA, the steroid-sparing effect of ADA was confirmed.
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Affiliation(s)
- Mayuko Shinagawa
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Kenichi Namba
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Kazuomi Mizuuchi
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Daiju Iwata
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Keitaro Hase
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Kayo Suzuki
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Kiriko Hirooka
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Nobuyoshi Kitaichi
- Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Japan
| | - Miki Hiraoka
- Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Japan
| | - Susumu Ishida
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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Chua JV, Baddley JW. Anti-tumor Necrosis Factor-Alpha Agents. INFECTIOUS COMPLICATIONS IN BIOLOGIC AND TARGETED THERAPIES 2022:69-87. [DOI: 10.1007/978-3-031-11363-5_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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A Fatal Case of Concurrent Disseminated Tuberculosis, Pneumocystis Pneumonia, and Bacterial Septic Shock in a Patient with Rheumatoid Arthritis Receiving Methotrexate, Glucocorticoid, and Tocilizumab: An Autopsy Report. Case Rep Rheumatol 2021; 2021:7842049. [PMID: 34532148 PMCID: PMC8440108 DOI: 10.1155/2021/7842049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 08/30/2021] [Indexed: 12/02/2022] Open
Abstract
Recently, treatment for rheumatoid arthritis has dramatically improved but increases the risk of bacterial and opportunistic infections. Herein, we report a fatal case of concurrent disseminated tuberculosis, pneumocystis pneumonia, and septic shock due to pyelonephritis caused by extended-spectrum β-lactamase-producing Escherichia coli in a patient with rheumatoid arthritis who received methotrexate, glucocorticoid, and tocilizumab. Despite undergoing intensive treatment, the patient developed respiratory failure and died after 7 days of admission. An autopsy indicated that pulmonary tuberculosis were the ultimate causes of death, while pyelonephritis was controlled.
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Takeuchi T, Nishikawa K, Yamada F, Ohshima S, Inoue M, Yoshioka Y, Yamanaka H. Real-world safety and efficacy of CT-P13, an infliximab biosimilar, in Japanese rheumatoid arthritis patients naïve to or switched from biologics. Mod Rheumatol 2021; 32:718-727. [PMID: 34918129 DOI: 10.1093/mr/roab068] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/12/2021] [Accepted: 08/15/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVES The aim of this post-marketing surveillance (PMS) study is to evaluate the real-world safety and efficacy of CT-P13, the first biosimilar of infliximab (IFX). METHODS Japanese patients with rheumatoid arthritis were prospectively registered from November 2014 and followed up for 1 year. RESULTS Of 794 patients in the analysis set, 318 patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) showed an immediate decrease in Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) and increased remission rate (DAS28-CRP < 2.6). In patients who switched from IFX to CT-P13 for non-medical reasons (n = 374), the low DAS28-CRP due to previous IFX treatment decreased further with continued CT-P13 therapy. As in naïve patients, patients who switched from other bDMARDs, mainly for medical reasons (n = 102), responded similarly to CT-P13. CT-P13 in this PMS and IFX in a previous PMS had similar adverse reaction profiles, although the incidence rate in naïve patients in this current PMS was lower due to earlier initiation of CT-P13 therapy. CONCLUSIONS CT-P13 showed excellent effectiveness as first-line therapy, no clinical difficulties in switching from IFX, and clinical improvement in patients who failed other bDMARDs. CT-P13 could be a cost-effective alternative to IFX in the treatment of rheumatoid arthritis.
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Affiliation(s)
- Tsutomu Takeuchi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Kiyohiro Nishikawa
- Quality & Pharmacovigilance Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo, Japan.,Asajes Ventures,Tokyo, Japan
| | - Fumika Yamada
- Quality & Pharmacovigilance Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo, Japan
| | - Shiro Ohshima
- Department of Rheumatology and Allergology, National Hospital Organization, Osaka Minami Medical Center, Osaka, Japan
| | - Makoto Inoue
- Department of Rheumatology, Inoue Hospital, Takasaki, Gunma, Japan
| | - Yutaka Yoshioka
- Department of Rheumatology, Handa City Hospital, Handa, Aichi, Japan
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Oka Y, Kodera T, Takeshita M, Shirota Y, Takeda T, Tsutsumi T, Kameoka J. Decrease of infectious complications in outpatients with autoimmune diseases from 2019 to 2020 under the COVID-19 pandemic: A single-centre, retrospective cohort study in Japan. Mod Rheumatol 2021; 32:444-451. [PMID: 34918128 PMCID: PMC8500052 DOI: 10.1093/mr/roab080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/11/2021] [Accepted: 08/27/2021] [Indexed: 11/13/2022]
Abstract
OBJECTIVES To examine how the novel coronavirus disease (COVID-19) has changed infectious complications in outpatients with autoimmune diseases. METHODS We performed a retrospective, record-linked cohort study and questionnaire about lifestyle changes in patients who visited our department in 2019 and 2020. RESULTS We surveyed 1316 outpatients in 2019 and 1284 in 2020. The most common underlying diseases were rheumatoid arthritis (842 vs. 814) and systemic lupus erythematosus (SLE) (126 vs. 127). No significant difference in median age (66 vs. 67 years), respiratory comorbidities (30.4% vs. 32.0%), or corticosteroid use (42.2% vs. 44.3%) was found between the years. Immunomodulating agents were used more in 2020 (33.1% vs. 39.7%, p < .001). Total number of infections (28.0/100 vs. 19.4/100 person-years), pneumonia (3.6 vs. 1.6), influenza (2.1 vs. 0.1), and nonviral dermatological infections (3.8 vs. 2.1) were significantly lower in 2020. No significant difference was found for herpes zoster (2.2 vs. 1.8), urinary tract infections (3.3 vs. 3.8), or gastrointestinal infections (2.9 vs. 3.0). According to the questionnaire, 75% of the respondents became more conscious about wearing masks and 81% began to use hand sanitizer during the pandemic. CONCLUSION Under the COVID-19 pandemic, some infectious complications have decreased in outpatients with autoimmune diseases.
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Affiliation(s)
- Yumiko Oka
- Department of Hematology and Rheumatology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan
| | - Takao Kodera
- Department of Hematology and Rheumatology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan
| | - Miki Takeshita
- Department of Hematology and Rheumatology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan
| | - Yuko Shirota
- Department of Hematology and Rheumatology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan
| | - Tomoki Takeda
- Department of Hematology and Rheumatology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan
| | - Tomomi Tsutsumi
- Department of Hematology and Rheumatology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan
| | - Junichi Kameoka
- Department of Hematology and Rheumatology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan
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Al-Sohaim A, Bawazir AS, Al-Turki T, Alsafi EO, Al-Roqy A, Layqah L, Baharoone SA. The risk of tuberculosis infection in 410 Saudipatients receiving adalimumab therapy. Ann Saudi Med 2021; 41:285-292. [PMID: 34618606 PMCID: PMC8497010 DOI: 10.5144/0256-4947.2021.285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Adalimumab is a fully humanized monoclonal antibody inhibitor of tumor necrosis factor-a used to treat various autoimmune disorders. Adalimumab poses a risk for tuberculosis (TB) infection, especially in countries where TB is endemic. OBJECTIVE Determine the rate of TB infection after adalimumab therapy in Saudi Arabia. DESIGN Medical record review. SETTINGS Tertiary care center in Riyadh. PATIENTS AND METHODS Demographic and clinical data were retrieved from the electronic healthcare records of all patients who received adalimumab treatment from 2015 to 2019. MAIN OUTCOME MEASURES Occurrence of TB after adalimumab therapy. SAMPLE SIZE 410 patients (median ([QR] age, 37 [28], range 4-81 years), 40% males RESULTS: Rheumatoid arthritis was the most frequent indication (n=153, 37%). The patients were followed for a mean of 36 (8.9) months. No case of TB infection or reactivation was observed. An inter-feron-gamma release assay (IGRA) was requested in 353/391 (90.3%) patients, prior to initiating therapy. The IGRA was positive in 26 cases (6.6%). The IGRA-positive patients received isoniazid prophylactically. Bacterial infectious complications of adalimumab therapy occurred in 12 (2.9%) patients. Urinary tract infection was the most frequent complication (culture requested in 48 patients, positive in 8). CONCLUSION Adalimumab treatment was not associated with a risk of TB disease or TB reactivation in our cohort over the follow-up observation period. No TB reactivation occurred with adalimumab therapy when TB prophylaxis was used. The positive IGRA rate in patients on adalimumab treatment was low (7%). LIMITATIONS Single center and one geographical area in Saudi Arabia. CONFLICT OF INTEREST None.
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Affiliation(s)
- Abdullah Al-Sohaim
- From the Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | | | - Turki Al-Turki
- From the Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Eiman Omar Alsafi
- From the Department of Quality Management, King Saud Chest Specialty Hospital, Riyadh, Saudi Arabia
| | - Abdullah Al-Roqy
- From the Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Layla Layqah
- From the Research Office, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.,From the King Saud bin Abdul-Aziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Salim Alawi Baharoone
- From the Department of Intensive Care, King Abdulaziz Medical City, Riyadh, Saudi Arabia
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Banerjee R, Ali RAR, Wei SC, Adsul S. Biologics for the Management of Inflammatory Bowel Disease: A Review in Tuberculosis-Endemic Countries. Gut Liver 2021; 14:685-698. [PMID: 33191310 PMCID: PMC7667923 DOI: 10.5009/gnl19209] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 11/01/2019] [Accepted: 11/25/2019] [Indexed: 12/17/2022] Open
Abstract
The advent of biologics and biologic therapy has transformed the management of inflammatory bowel disease (IBD) with enhanced early and adequate responses to treatment, fewer hospitalizations, a reduced need for surgery, and unprecedented outcomes including complete mucosal and histologic healing. However, an important issue with the use of anti-tumor necrosis factor (anti-TNF) agents in IBD is the increased risk of tuberculosis (TB). This is compounded by the diagnostic dilemma when differentiating between Crohn’s disease and gastrointestinal TB, and the potentially serious consequences of initiating an incorrect treatment in the case of misdiagnosis. The interplay between IBD and TB is most relevant in Asia, where more than 60% of the 10.4 million new TB cases in 2016 were reported. A number of studies have reported an increased risk of TB with anti-TNF agents, including in patients who had tested negative for TB prior to treatment initiation. The limited evidence currently available regarding adhesion molecule antagonists such as vedolizumab suggests a comparatively lower risk of TB, thus making them a promising option for IBD management in TB-endemic regions. This comprehensive review examines the available literature on the risk of TB with the use of biologics in the TB-endemic regions of Asia, focusing on the diagnostic dilemma, the risk of reactivation, and the optimized management algorithms for latent and active disease.
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Affiliation(s)
- Rupa Banerjee
- IBD Center, Asian Institute of Gastroenterology, Hyderabad, India
| | - Raja Affendi Raja Ali
- Gastroenterology Unit, Department of Medicine, Faculty of Medicine, The National University of Malaysia, Kuala Lumpur, Malaysia
| | - Shu Chen Wei
- Department of Internal Medicine, IBD Clinical and Basic Research Integrated Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shashi Adsul
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
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Takei H, Nishina N, Namkoong HO, Suzuki K, Uwamino Y, Hasegawa N, Takeuchi T. Rheumatoid arthritis with nontuberculous mycobacterial pulmonary disease: a retrospective, single-centre cohort study. Mod Rheumatol 2021; 32:534-540. [PMID: 34910202 DOI: 10.1093/mr/roab032] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 06/19/2021] [Accepted: 06/24/2021] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a rare but important comorbidity of rheumatoid arthritis (RA). Our objective was to investigate the association between NTM-PD and RA, especially regarding the immunosuppressive treatment of RA such as biological disease-modifying antirheumatic drugs (bDMARDs). METHODS We conducted a retrospective, single-centre cohort study. All RA patients regularly followed up at our rheumatology division in December 2012 were included in the study, and followed for 5 years. RESULTS At baseline, 26 of 1639 RA patients had NTM-PD. During the observation period, 14 were newly diagnosed with NTM-PD. For new diagnosis of NTM-PD, bDMARD use at baseline was not a significant risk factor. Among the 40 patients with NTM-PD, 16 were treated with a total of 27 bDMARDs after NTM-PD diagnosis. They did not present with a greater exacerbation of NTM-PD than those not treated with bDMARDs (25 vs. 17%, p = .52). A total of 55 patients died, but nobody died of NTM-PD. NTM-PD was not associated with worse mortality in multivariate analysis (hazard ratio, 2.0; 95% CI, 0.6-6.4; p = .26). CONCLUSIONS Biological DMARD was not associated with worse prognosis of NTM-PD. Careful use of bDMARDs could be tolerated in RA patients with NTM-PD.
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Affiliation(s)
- Hiroshi Takei
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Naoshi Nishina
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - H O Namkoong
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Katsuya Suzuki
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Yoshifumi Uwamino
- Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.,Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Naoki Hasegawa
- Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan
| | - Tsutomu Takeuchi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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Sagami S, Nishikawa K, Yamada F, Suzuki Y, Watanabe M, Hibi T. Post-marketing analysis for biosimilar CT-P13 in inflammatory bowel disease compared with external data of originator infliximab in Japan. J Gastroenterol Hepatol 2021; 36:2091-2100. [PMID: 33450057 PMCID: PMC8451807 DOI: 10.1111/jgh.15399] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/27/2020] [Accepted: 01/01/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM CT-P13, an infliximab (IFX) biosimilar, was approved for treatment of inflammatory bowel disease. However, no comparison with the originator IFX in this indication has been conducted in Japan where endemic levels of tuberculosis and hepatitis virus infection are not low. We evaluated the safety and efficacy in real-world data of CT-P13 and compared with originator IFX data in Japan. METHODS In a prospective post-marketing surveillance (PMS) study, patients who received CT-P13 in a 28-month period from January 2015 were followed up for 2 years. By conducting Japanese administrative database search (DBS) for the same period of PMS, data of the originator IFX including treatment persistence, tuberculosis incidence, and liver injury were analyzed retrospectively and compared with the corresponding PMS data of CT-P13. RESULTS CT-P13 persistence in PMS (n = 640) and IFX persistence in DBS (n = 4113) were almost similar between patients who switched from the originator and patients who continued on the originator, and also between the biologics-naïve patient groups. There were no differences in the incidences of tuberculosis and hepatic injury (Tuberculosis: 2 patients [0.31%] with CT-P13, 10 patients [0.24%] with the originator, P = 0.75; Hepatic injury: 18.5% with CT-P13, 15.4% with the originator, P = 0.22). Most of the patients with hepatic injury continued treatment in PMS and DBS at similar rates (80.8% vs 83.6%, P = 0.65). CONCLUSION The results of long-term PMS of CT-P13 compared with external reference data from an administrative database suggested that the biosimilar and its originator were comparably useful in real-world clinical practice.
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Affiliation(s)
- Shintaro Sagami
- Center for Advanced IBD Research and TreatmentKitasato University Kitasato Institute HospitalTokyoJapan,Department of Gastroenterology and HepatologyKitasato University Kitasato Institute HospitalTokyoJapan
| | - Kiyohiro Nishikawa
- Quality and Pharmacovigilance DivisionPharmaceuticals Group, Nippon Kayaku Co., Ltd.TokyoJapan,Asajes VenturesTokyoJapan
| | - Fumika Yamada
- Quality and Pharmacovigilance DivisionPharmaceuticals Group, Nippon Kayaku Co., Ltd.TokyoJapan
| | - Yasuo Suzuki
- IBD CenterToho University Sakura Medical CenterChibaJapan
| | - Mamoru Watanabe
- Department of Gastroenterology and HepatologyTokyo Medical and Dental UniversityTokyoJapan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and TreatmentKitasato University Kitasato Institute HospitalTokyoJapan
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Charpentier E, Ménard S, Marques C, Berry A, Iriart X. Immune Response in Pneumocystis Infections According to the Host Immune System Status. J Fungi (Basel) 2021; 7:jof7080625. [PMID: 34436164 PMCID: PMC8399367 DOI: 10.3390/jof7080625] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/28/2021] [Accepted: 07/29/2021] [Indexed: 12/12/2022] Open
Abstract
The host immune response is critical in Pneumocystis pneumonia (PCP). Immunocompetent hosts can eliminate the fungus without symptoms, while immunodeficient hosts develop PCP with an unsuitable excessive inflammatory response leading to lung damage. From studies based on rodent models or clinical studies, this review aimed to better understand the pathophysiology of Pneumocystis infection by analysing the role of immune cells, mostly lymphocytes, according to the immune status of the infected host. Hence, this review first describes the immune physiological response in infected immunocompetent hosts that are able to eliminate the fungus. The objective of the second part is to identify the immune elements required for the control of the fungus, focusing on specific immune deficiencies. Finally, the third part concentrates on the effect of the different immune elements in immunocompromised subjects during PCP, to better understand which cells are detrimental, and which, on the contrary, are beneficial once the disease has started. This work highlights that the immune response associated with a favourable outcome of the infection may differ according to the immune status of the host. In the case of immunocompetency, a close communication between B cells and TCD4 within tertiary lymphocyte structures appears critical to activate M2 macrophages without much inflammation. Conversely, in the case of immunodeficiency, a pro-inflammatory response including Th1 CD4, cytotoxic CD8, NK cells, and IFNγ release seems beneficial for M1 macrophage activation, despite the impact of inflammation on lung tissue.
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Affiliation(s)
- Eléna Charpentier
- Department of Parasitology-Mycology, Toulouse University Hospital, 31059 Toulouse, France;
- Infinity, Inserm, CNRS, University of Toulouse III, 31024 Toulouse, France; (S.M.); (C.M.)
- Correspondence: (E.C.); (X.I.)
| | - Sandie Ménard
- Infinity, Inserm, CNRS, University of Toulouse III, 31024 Toulouse, France; (S.M.); (C.M.)
| | - Catherine Marques
- Infinity, Inserm, CNRS, University of Toulouse III, 31024 Toulouse, France; (S.M.); (C.M.)
| | - Antoine Berry
- Department of Parasitology-Mycology, Toulouse University Hospital, 31059 Toulouse, France;
- Infinity, Inserm, CNRS, University of Toulouse III, 31024 Toulouse, France; (S.M.); (C.M.)
| | - Xavier Iriart
- Department of Parasitology-Mycology, Toulouse University Hospital, 31059 Toulouse, France;
- Infinity, Inserm, CNRS, University of Toulouse III, 31024 Toulouse, France; (S.M.); (C.M.)
- Correspondence: (E.C.); (X.I.)
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Kucharzik T, Ellul P, Greuter T, Rahier JF, Verstockt B, Abreu C, Albuquerque A, Allocca M, Esteve M, Farraye FA, Gordon H, Karmiris K, Kopylov U, Kirchgesner J, MacMahon E, Magro F, Maaser C, de Ridder L, Taxonera C, Toruner M, Tremblay L, Scharl M, Viget N, Zabana Y, Vavricka S. ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease. J Crohns Colitis 2021; 15:879-913. [PMID: 33730753 DOI: 10.1093/ecco-jcc/jjab052] [Citation(s) in RCA: 230] [Impact Index Per Article: 57.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- T Kucharzik
- Department of Gastroenterology, Klinikum Lüneburg, University of Hamburg, Lüneburg, Germany
| | - P Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | - T Greuter
- University Hospital Zürich, Department of Gastroenterology and Hepatology, Zürich, Switzerland, and Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois CHUV, University Hospital Lausanne, Lausanne, Switzerland
| | - J F Rahier
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Yvoir, Belgium
| | - B Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium, and Department of Chronic Diseases, Metabolism and Ageing, TARGID-IBD, KU Leuven, Leuven, Belgium
| | - C Abreu
- Infectious Diseases Service, Centro Hospitalar Universitário São João, Porto, Portugal
- Instituto de Inovação e Investigação em Saúde [I3s], Faculty of Medicine, Department of Medicine, University of Porto, Portugal
| | - A Albuquerque
- Gastroenterology Department, St James University Hospital, Leeds, UK
| | - M Allocca
- Humanitas Clinical and Research Center - IRCCS -, Rozzano [Mi], Italy
- Humanitas University, Department of Biomedical Sciences, Milan, Italy
| | - M Esteve
- Hospital Universitari Mútua Terrassa, Digestive Diseases Department, Terrassa, Catalonia, and Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas CIBERehd, Madrid, Spain
| | - F A Farraye
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - H Gordon
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, UK
| | - K Karmiris
- Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Greece
| | - U Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - J Kirchgesner
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Department of Gastroenterology, Paris, France
| | - E MacMahon
- Department of Infectious Diseases, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - F Magro
- Gastroenterology Department, Centro Hospitalar São João, Porto, Portugal
- Institute of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Portugal
| | - C Maaser
- Outpatient Department of Gastroenterology, Department of Geriatrics, Klinikum Lüneburg, University of Hamburg, Lüneburg, Germany
| | - L de Ridder
- Department of Paediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - C Taxonera
- IBD Unit, Department of Gastroenterology, Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos [IdISSC], Madrid, Spain
| | - M Toruner
- Ankara University School of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - L Tremblay
- Centre Hospitalier de l'Université de Montréal [CHUM] Pharmacy Department and Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
| | - M Scharl
- University Hospital Zürich, Department of Gastroenterology and Hepatology, Zürich, Switzerland
| | - N Viget
- Department of Infectious Diseases, Tourcoing Hospital, Tourcoing, France
| | - Y Zabana
- Hospital Universitari Mútua Terrassa, Digestive Diseases Department, Terrassa, Catalonia, and Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas CIBERehd, Madrid, Spain
| | - S Vavricka
- University Hospital Zürich, Department of Gastroenterology and Hepatology, Zürich, Switzerland
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Vicente-Rabaneda EF, Atienza-Mateo B, Blanco R, Cavagna L, Ancochea J, Castañeda S, González-Gay MÁ. Efficacy and safety of abatacept in interstitial lung disease of rheumatoid arthritis: A systematic literature review. Autoimmun Rev 2021; 20:102830. [PMID: 33887489 DOI: 10.1016/j.autrev.2021.102830] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 02/11/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Interstitial lung disease (ILD) is a serious complication that represents the second leading cause of death in patients with rheumatoid arthritis (RA). Treatment of RA-ILD remains controversial. The absence of randomized clinical trials and specific ACR or EULAR therapeutic guidelines makes it difficult to establish solid therapeutic recommendations on this issue. In this scenario, real-world data is especially valuable. OBJECTIVE To review the literature evidence on the efficacy and safety of abatacept (ABA) for the treatment of rheumatoid arthritis (RA) with associated interstitial lung disease (ILD), given its clinical relevance and the lack of consensus on its therapeutic management. METHODS PUBMED and EMBASE were searched from the date of approval of ABA to the end of 2020 using a combination of RA, ILD and ABA terms following PRISMA guidelines. Identified studies were evaluated by two independent investigators. RESULTS Nine original studies (1 case series and 8 observational studies) were selected for inclusion in the systematic review. No randomized trial or meta-analysis were identified. The mean age of patients ranged from 61.2 to 75 years and the mean RA duration varied from 7.4 to 18 years. Subcutaneous ABA (74.5%-91%) predominated in combination with conventional synthetic DMARDs (csDMARDs) (58%-75%), and it was used as first-line biologic agent in 22.8%-64.9% of the patients. The mean course of ILD ranged from 1 to 6.7 years, being usual and nonspecific interstitial pneumonia the most frequent patterns. Improvement or stabilization of ILD imaging (76.6%-92.7%) and FVC or DLCO (>85%) was described after a mean follow-up of 17.4-47.8 months, regardless of the pattern of lung involvement, being more remarkable in patients with shorter evolution of ILD. ABA led to significantly lower ILD worsening rates than TNF inhibitors (TNFi) and was associated with a 90% reduction in the relative risk of deterioration of ILD at 24 months of follow-up compared to TNFi and csDMARDs. Combination with methotrexate may have a corticoid-sparing effect. No unexpected adverse events were identified. CONCLUSIONS Current evidence suggests that ABA may be a plausible alternative to treat RA patients with ILD. It would be highly desirable to develop prospective randomized controlled studies to confirm these findings.
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Affiliation(s)
- Esther F Vicente-Rabaneda
- Rheumatology Division, Hospital Universitario de la Princesa, IIS-Princesa, C/Diego de León 62, 28006 Madrid, Spain.
| | - Belén Atienza-Mateo
- Rheumatology Division, Hospital Universitario Marqués de Valdecilla, Av. de Valdecilla 25, 39008 Santander, Cantabria, Spain.
| | - Ricardo Blanco
- Rheumatology Division, Hospital Universitario Marqués de Valdecilla, Av. de Valdecilla 25, 39008 Santander, Cantabria, Spain.
| | - Lorenzo Cavagna
- University and IRCCS Policlinico S. Matteo Foundation, Viale Camillo Golgi 19, 27100 Pavia, Italy.
| | - Julio Ancochea
- Pneumology Division, Hospital Universitario de la Princesa, IIS-Princesa, C/Diego de León 62, 28006 Madrid, Spain; Cátedra UAM-Roche, EPID-Future, Medicine Department, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
| | - Santos Castañeda
- Rheumatology Division, Hospital Universitario de la Princesa, IIS-Princesa, C/Diego de León 62, 28006 Madrid, Spain; Cátedra UAM-Roche, EPID-Future, Medicine Department, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
| | - Miguel Á González-Gay
- Rheumatology Division, Hospital Universitario Marqués de Valdecilla, Av. de Valdecilla 25, 39008 Santander, Cantabria, Spain; University of Cantabria, Santander, Spain; University of Witwatersrand, Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, South Africa.
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Miyagawa H, Hara H, Araya J, Minagawa S, Numata T, Umezawa Y, Asahina A, Nakagawa H, Kuwano K. Characteristics of anti-IL-17/23 biologics-induced interstitial pneumonia in patients with psoriasis. PLoS One 2021; 16:e0245284. [PMID: 33411857 PMCID: PMC7790374 DOI: 10.1371/journal.pone.0245284] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 12/24/2020] [Indexed: 12/26/2022] Open
Abstract
Objectives Anti-IL-17/23 biologics are increasingly used to treat psoriasis. We aimed to elucidate characteristics of drug-induced interstitial pneumonia (DIIP) caused by anti-IL-17/23 biologics. Methods We retrospectively analyzed the clinical data of psoriasis patients treated with anti-IL-17/23 biologics. Chest CT was performed to evaluate DIIP. Serum KL-6 levels were measured before treatment (baseline) and during treatment. Results A total of 603 psoriasis patients were treated with anti-IL-17/23 biologics with mean follow-up of 21.1 months. Six patients developed DIIP at mean 14 months after initiation of the therapy. Older age, higher baseline KL-6 value and more frequent pre-existing IPs were associated with development of DIIP by univariate analysis. At the onset of DIIP, elevated serum KL-6 levels with concomitantly increased ground glass opacity (GGO) in Chest CT were demonstrated. DIIP was improved by only cessation of causative agents in five patients but steroid therapy was needed in one patient. Conclusions DIIP is a plausible complication of anti-IL-17/23 biologics. Age, baseline KL-6 level and underlying IP could be the risk factors for DIIP development. Serum KL-6 levels and chest CT are useful for not only predicting but also detecting DIIP caused by anti-IL-17/23 biologics.
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Affiliation(s)
- Hanae Miyagawa
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- * E-mail: (HH); (HM)
| | - Hiromichi Hara
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- * E-mail: (HH); (HM)
| | - Jun Araya
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Shunsuke Minagawa
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takanori Numata
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yoshinori Umezawa
- Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan
| | - Akihiko Asahina
- Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan
| | - Hidemi Nakagawa
- Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan
| | - Kazuyoshi Kuwano
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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Iba A, Tomio J, Yamana H, Sugiyama T, Yoshiyama T, Kobayashi Y. Tuberculosis screening and management of latent tuberculosis infection prior to biologic treatment in patients with immune-mediated inflammatory diseases: A longitudinal population-based analysis using claims data. Health Sci Rep 2020; 3:e216. [PMID: 33336081 PMCID: PMC7731986 DOI: 10.1002/hsr2.216] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 11/10/2020] [Accepted: 11/12/2020] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND AND AIM Screening for tuberculosis before treating with biologic agents is recommended in patients with immune-mediated inflammatory diseases (IMIDs). We conducted this study to identify adherence to the recommended practice in a real-world setting in Japan. METHODS We used a community-based insurance claims database in a city in the Greater Tokyo Area in Japan. Between July 2012 and January 2019, we enrolled patients with IMIDs in the age range 15 to 74 years who had initiated biologic therapy. Tuberculosis screening was defined as (a) interferon-γ release assay and/or a tuberculin skin test (IGRA/TST) and (b) IGRA/TST and X-ray and/or CT scan (X-ray/CT) within 2 months before starting biologic agents. We analyzed the proportions of patients who underwent tuberculosis screening and their association with the patient- and treatment-related factors and treatment for latent tuberculosis infection (LTBI). RESULTS Of 421 patients presumed to have initiated biologic therapy, 202 (48%) underwent IGRA/TST and 169 (40%) underwent IGRA/TST and X-ray/CT. Patients aged 65 to 74 years were more likely to undergo tuberculosis screening than those aged 45 to 64 years. Compared to infliximab, IGRA/TST was less frequently performed in patients treated with etanercept, adalimumab, golimumab, abatacept, and tocilizumab. Treatment for LTBI was provided to 67 (16%) patients. Proportions of patients receiving LTBI treatment did not significantly differ according to the screening status. CONCLUSION There was low adherence to the recommendations for tuberculosis screening and prophylactic treatment before biologic therapy. It is necessary to continue alerting clinical practitioners to the importance of screening for tuberculosis and treatment for LTBI.
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Affiliation(s)
- Arisa Iba
- Department of Public HealthGraduate School of Medicine, The University of TokyoTokyoJapan
| | - Jun Tomio
- Department of Public HealthGraduate School of Medicine, The University of TokyoTokyoJapan
| | - Hayato Yamana
- Department of Health Services ResearchGraduate School of Medicine, The University of TokyoTokyoJapan
| | - Takehiro Sugiyama
- Diabetes and Metabolism Information CenterResearch Institute, National Center for Global Health and MedicineTokyoJapan
- Institute for Global Health Policy Research, Bureau of International Health CooperationNational Center for Global Health and MedicineTokyoJapan
- Department of Health Services Research, Faculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Takashi Yoshiyama
- Research Institute of TuberculosisJapan Anti Tuberculosis AssociationTokyoJapan
| | - Yasuki Kobayashi
- Department of Public HealthGraduate School of Medicine, The University of TokyoTokyoJapan
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