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Abhiraman GC, Householder KD, Rodriguez GE, Glassman CR, Saxton RA, Breuer CB, Wilson SC, Su L, Yen M, Hsu C, Pillarisetty VG, Reticker-Flynn NE, Garcia KC. Redirecting immune signaling with cytokine adaptors. Nat Commun 2025; 16:2432. [PMID: 40069219 PMCID: PMC11897282 DOI: 10.1038/s41467-025-57681-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 02/28/2025] [Indexed: 03/15/2025] Open
Abstract
Cytokines are signaling molecules that coordinate complex immune processes and are frequently dysregulated in disease. While cytokine blockade has become a common therapeutic modality, cytokine agonism has had limited utility due to the widespread expression of cytokine receptors with pleiotropic effects. To overcome this limitation, we devise an approach to engineer molecular switches, termed cytokine adaptors, that transform one cytokine signal into an alternative signal with a different functional output. Endogenous cytokines act to nucleate the adaptors, converting the cytokine-adaptor complex into a surrogate agonist for a different cytokine pathway. In this way, cytokine adaptors, which have no intrinsic agonist activity, can function as conditional, context-dependent agonists. We develop cytokine adaptors that convert IL-10 or TGF-β into IL-2 receptor agonists to reverse T cell suppression. We also convert the pro-inflammatory cytokines IL-23 or IL-17 into immunosuppressive IL-10 receptor agonists. Thus, we show that cytokine adaptors can convert immunosuppressive cytokines into immunostimulatory cytokines, or vice versa. Unlike other methods of immune conversion that require cell engineering, cytokine adaptors are soluble molecules that leverage endogenous cues from the microenvironment to drive context-specific signaling.
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Affiliation(s)
- Gita C Abhiraman
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA, 94305, USA
- Program in Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Karsten D Householder
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA, 94305, USA
- Program in Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Grayson E Rodriguez
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA, 94305, USA
- Program in Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Caleb R Glassman
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA, 94305, USA
| | - Robert A Saxton
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA, 94305, USA
| | - Cort B Breuer
- Program in Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Steven C Wilson
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA, 94305, USA
| | - Leon Su
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA, 94305, USA
| | - Michelle Yen
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA, 94305, USA
| | - Cynthia Hsu
- Department of Surgery, University of Washington School of Medicine, Seattle, WA, 98112, USA
| | - Venu G Pillarisetty
- Department of Surgery, University of Washington School of Medicine, Seattle, WA, 98112, USA
| | - Nathan E Reticker-Flynn
- Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - K Christopher Garcia
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA, 94305, USA.
- Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA.
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Isa M, Ramos MRR, Kamal S. Infection Risk in Biological Disease-Modifying Anti-rheumatic Drugs. Cureus 2025; 17:e80634. [PMID: 40236366 PMCID: PMC11998624 DOI: 10.7759/cureus.80634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/14/2025] [Indexed: 04/17/2025] Open
Abstract
Rheumatology patients on biological disease-modifying anti-rheumatic drugs (bDMARDs) have been proposed to be at a higher risk of infections. Our review summarizes the current evidence behind this theory as well as explores which factors predispose patients to various infections, which agents are more likely to cause infections, and which infections are common in these patients. We also aim to explore updated guidelines on infection prevention in patients on bDMARDs.
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Affiliation(s)
- Mourushi Isa
- General Medicine, Northern Health, Melbourne, AUS
| | | | - Shahed Kamal
- General Medicine, Northern Health, Melbourne, AUS
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Tyrberg T, Hagberg L, Nilsson S, Grahn A. Incidence and Risk Factors for Varicella-Zoster Virus-Associated Central Nervous System Infections: A Nationwide Swedish Retrospective Case-Control Study. J Med Virol 2025; 97:e70166. [PMID: 39865326 PMCID: PMC11771675 DOI: 10.1002/jmv.70166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 12/01/2024] [Accepted: 12/28/2024] [Indexed: 01/28/2025]
Abstract
The determinants of varicella-zoster virus (VZV)-associated central nervous system (CNS) infection have not been fully elucidated. This study aimed to investigate the incidence and risk factors, including immunosuppression, for different manifestations of VZV-associated CNS infection. Patient registers were used to include adults diagnosed with VZV-associated CNS infections between 2010 and 2019 in Sweden. Nationwide registers covering specialized care, and regional registers covering primary care, were used. Controls without a VZV diagnosis during the study period were matched by age and sex. Risk factors were calculated using multivariable logistic regression. A total of 1488 adult cases with VZV-associated CNS infection were identified, yielding an incidence of 1.92/100 000 person-years, which increased over the study period. Meningitis was the most frequent (45%), followed by encephalitis (38%), and Ramsay Hunt syndrome (17%). The highest incidence was observed in individuals over 70 years of age (4.15/100 000 person-years), in whom encephalitis was most common. Statistically significant risk factors for VZV-associated CNS infection were HIV, hematological cancer, treatment with specific immunosuppressants or glucocorticoids, chronic obstructive pulmonary disease, diabetes, solid cancer, stroke, and congestive heart failure. Encephalitis was associated with older age, more immunosuppressive conditions, and more comorbidities than other manifestations. In conclusion, VZV is a common cause of adult viral CNS infection, for which elderly individuals with immunosuppressive or comorbid conditions are at the highest risk. The strongest risk factors found were HIV, hematological cancer, and treatment with specific immunosuppressants or high-dose glucocorticoids.
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Affiliation(s)
- Tobias Tyrberg
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of Infectious DiseasesSahlgrenska University HospitalGothenburgSweden
| | - Lars Hagberg
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of Infectious DiseasesSahlgrenska University HospitalGothenburgSweden
| | - Staffan Nilsson
- Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Anna Grahn
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of Infectious DiseasesSahlgrenska University HospitalGothenburgSweden
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Ababneh O, Nishizaki D, Kato S, Kurzrock R. Tumor necrosis factor superfamily signaling: life and death in cancer. Cancer Metastasis Rev 2024; 43:1137-1163. [PMID: 39363128 PMCID: PMC11554763 DOI: 10.1007/s10555-024-10206-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 08/13/2024] [Indexed: 10/05/2024]
Abstract
Immune checkpoint inhibitors have shaped the landscape of cancer treatment. However, many patients either do not respond or suffer from later progression. Numerous proteins can control immune system activity, including multiple tumor necrosis factor (TNF) superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) members; these proteins play a complex role in regulating cell survival and death, cellular differentiation, and immune system activity. Notably, TNFSF/TNFRSF molecules may display either pro-tumoral or anti-tumoral activity, or even both, depending on tumor type. Therefore, TNF is a prototype of an enigmatic two-faced mediator in oncogenesis. To date, multiple anti-TNF agents have been approved and/or included in guidelines for treating autoimmune disorders and immune-related toxicities after immune checkpoint blockade for cancer. A confirmed role for the TNFSF/TNFRSF members in treating cancer has proven more elusive. In this review, we highlight the cancer-relevant TNFSF/TNFRSF family members, focusing on the death domain-containing and co-stimulation members and their signaling pathways, as well as their complicated role in the life and death of cancer cells.
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Affiliation(s)
- Obada Ababneh
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan.
| | - Daisuke Nishizaki
- Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, CA, USA
| | - Shumei Kato
- Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, CA, USA
| | - Razelle Kurzrock
- WIN Consortium, Paris, France.
- Department of Medicine, MCW Cancer Center, Milwaukee, WI, USA.
- Department of Oncology, University of Nebraska, Omaha, NE, USA.
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Fang YF, Chang SH, Kuo CF, See LC. Safety outcomes of tocilizumab and tofacitinib treatment for rheumatoid arthritis: Target trial emulation. Int J Rheum Dis 2024; 27:e15406. [PMID: 39523495 DOI: 10.1111/1756-185x.15406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 10/04/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVES Biological disease-modifying antirheumatic drugs have been the primary treatment option for moderate to severe rheumatoid arthritis (RA) in Taiwan since 2010. Tocilizumab is an interleukin-6 receptor inhibitor, whereas tofacitinib is a Janus kinase inhibitor. The two medications were indicated to treat RA by direct and indirect inhibition of interleukin-6 cytokine. We compared the safety outcomes of tocilizumab and tofacitinib in patients with RA in real-world clinical settings, following the 7 key components of target trial emulation (TTE). METHODS The data source was the Taiwan National Health Insurance Research Database. Patients with RA between 2010 and 2018 were eligible and assigned to either tocilizumab or tofacitinib based on their first prescription of these two medications. The index date was set as the first prescription date of either study medication. Propensity score stabilized weighting (PSSW) was used to balance the characteristics between the two medication groups. The incidences of safety outcomes were all-cause mortality, cancer, coronary heart disease, stroke, venous thrombosis events, tuberculosis, joint replacement events, and herpes zoster infection. The intention-to-treat (ITT) effect was commenced from the index date until the study outcomes, independently, 3 years, withdrawal, or December 31, 2021, whichever occurred first. For the per-protocol (PP) effect, patients were required to maintain the same medical group during the entire follow-up period. RESULTS A total of 2125 patients with RA who were prescribed tocilizumab (n = 844) or tofacitinib (n = 1281) were included in this study. The mean follow-up duration was 2.78 years in the tocilizumab group and 2.83 years in the tofacitinib group. For ITT, the sample sizes were 721 and 1196 for the tocilizumab and tofacitinib, respectively, after PSSW. A substantially lower incidence rate of herpes zoster infection (per 100 patient-years) was observed in the tocilizumab group (3.67) than in the tofacitinib group (7.61), with a hazard ratio of 0.48 (95%CI =0.37-0.63; p < .0001). All-cause mortality, cancer, coronary heart disease, stroke, total hip replacement, and tuberculosis were similar between the two medication groups. For PP, the sample sizes were 619 and 1085 for the tocilizumab and tofacitinib, respectively, after PSSW. The results of the PP analysis were similar to those of the ITT analysis. CONCLUSIONS Tocilizumab and tofacitinib act along the same inflammatory pathway. A lower herpes zoster incident rate was observed in the tocilizumab group than in the tofacitinib group. The incidence rates of other safety concerns and mortality rates were comparable in both groups of patients with RA treated in real-world settings.
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Affiliation(s)
- Yao-Fan Fang
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan
| | - Shu-Hao Chang
- Department of Public Health, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Chang-Fu Kuo
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan
| | - Lai-Chu See
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan
- Department of Public Health, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
- Biostatistics Core Laboratory, Molecular Medicine Research Centre, Chang Gung University, Taoyuan City, Taiwan
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Zong Y, Kamoi K, Miyagaki M, Zhang J, Yang M, Zou Y, Ohno-Matsui K. Applications of Biological Therapy for Latent Infections: Benefits and Risks. Int J Mol Sci 2024; 25:9184. [PMID: 39273134 PMCID: PMC11394918 DOI: 10.3390/ijms25179184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
Biological therapies have revolutionized medical treatment by targeting the key mediators or receptors involved in inflammatory responses, thereby effectively suppressing inflammation and achieving beneficial outcomes. They are more advanced than conventional therapies using corticosteroids and immunosuppressants, offering effective solutions for autoimmune diseases, cancer, transplant rejection, and various infectious diseases, including coronavirus disease 2019. Although they exert low immunosuppressive effects, biological therapies can reactivate specific biological targets associated with infections. This review summarizes the currently available biological therapies and discusses their immunosuppressive mechanisms and clinical applications, highlighting the variations in the types and frequencies of infection recurrence induced by different biological agents. Additionally, this review describes the risk factors associated with various biological agents, thus aiding clinicians in selecting the most appropriate biological therapy.
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Affiliation(s)
- Yuan Zong
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Koju Kamoi
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Miki Miyagaki
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Jing Zhang
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Mingming Yang
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Yaru Zou
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Kyoko Ohno-Matsui
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
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Robinson SE, Varman R. Ramsay Hunt Syndrome Associated With Etanercept Treatment for Rheumatoid Arthritis: A Case Report and a Review of Literature. Cureus 2024; 16:e66531. [PMID: 39246920 PMCID: PMC11380981 DOI: 10.7759/cureus.66531] [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: 08/08/2024] [Indexed: 09/10/2024] Open
Abstract
A 38-year-old woman with rheumatoid arthritis treated with etanercept presented with complaints of ear pain. Over four days, the pain progressed to a vesicular rash and then facial nerve paralysis. The patient was diagnosed with Ramsay Hunt syndrome (RHS), a reactivation of the varicella zoster virus that specifically affects the seventh cranial nerve (CN VII). Etanercept is an anti-tumor necrosis factor (anti-TNF) agent that has known immunosuppressive effects. RHS occurs more commonly in immunocompromised states, such as the one induced by etanercept. To the best of our knowledge, this is one of the first reported cases of RHS with etanercept treatment.
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Affiliation(s)
- Sarah E Robinson
- Plastic and Reconstructive Surgery, Creighton University School of Medicine, Omaha, USA
| | - Rahul Varman
- Plastic and Reconstructive Surgery, Creighton University School of Medicine, Omaha, USA
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Jiang Z, Zou Y, Li G, Zhao S, Zhang W. Comparisons of infection events associated with tumor necrosis factor inhibitors in patients with inflammatory arthritis: A systematic review and network meta-analysis. Front Pharmacol 2024; 15:1376262. [PMID: 39070789 PMCID: PMC11273365 DOI: 10.3389/fphar.2024.1376262] [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: 01/25/2024] [Accepted: 06/10/2024] [Indexed: 07/30/2024] Open
Abstract
Objective: To compare the risk of infection in inflammatory arthritis patients treated with tumor necrosis factor (TNF) inhibitors. Methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception to 28 December 2023 for randomized controlled trials (RCTs) assessing TNF inhibitors and reporting infections. Subsequently, pairwise and network meta-analyses were conducted to determine odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Results: A total of 61 RCTs involving 20,458 patients were included. Pairwise meta-analysis revealed that certolizumab pegol was significantly associated with an increased risk of serious infection compared to placebo (OR:2.28, 95% CI: 1.13-4.62). Both adalimumab and certolizumab pegol were also significantly associated with an increased risk of any infection compared to placebo (OR:1.18, 95% CI: 1.06 to 1.30 and OR:1.40, 95% CI: 1.11 to 1.76, respectively). Moreover, a network meta-analysis indicated that certolizumab pegol and infliximab were associated with a higher risk of serious infection compared to other TNF inhibitors. In the cumulative ranking of any infection risk, certolizumab pegol had the highest risk compared with others. TNF inhibitors increased the risk of tuberculosis but not that of herpes zoster. Conclusion: Available evidence indicates etanercept and golimumab are likely associated with a lower risk of infection compared to other TNF inhibitors in inflammatory arthritis. For patients at a heightened risk of infection, prioritizing the use of etanercept and golimumab may be advisable to minimize patient risk. Systematic Review Registration: identifier CRD42022316577.
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Affiliation(s)
- Ziwei Jiang
- Department of Pharmacy, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Yue Zou
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Guangyao Li
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Sixuan Zhao
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Wei Zhang
- Department of Pharmacy, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
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Sen R, Riofrio M, Singh JA. A narrative review of the comparative safety of disease-modifying anti-rheumatic drugs used for the treatment of rheumatoid arthritis. Expert Opin Drug Saf 2024; 23:687-714. [PMID: 38695151 DOI: 10.1080/14740338.2024.2348575] [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: 11/29/2023] [Accepted: 04/24/2024] [Indexed: 05/24/2024]
Abstract
INTRODUCTION Disease-modifying anti-rheumatic drugs (DMARDs) have improved the outcomes of patients with rheumatoid arthritis (RA). DMARDs are classified into three categories: conventional synthetic DMARDs, biological DMARDs (including biosimilars), and targeted synthetic DMARDs. DMARDs, by way of their effect on the immune system, are associated with increased risk of adverse events, including infections, malignancies, cardiovascular disease, gastrointestinal perforations, and other less common events. AREAS COVERED In this narrative literature review performed with searches of the PubMed database from 1 January 2010 through 1 January 2023, we compare the risk of safety events between DMARDs using data from both randomized clinical trials and observational studies. EXPERT OPINION DMARD use in RA is associated with higher rates of serious infections, tuberculosis reactivation, opportunistic infections, and possibly malignancies. Specific biologic DMARDs and higher doses are associated with elevated risks of various adverse events (gastrointestinal perforations, thromboembolism, serious infection). Shared decision-making is paramount when choosing a treatment regimen for patients based on their own comorbidities. JAKi are the newest class of medications used for RA with robust safety data provided in clinical trials. However, more real-world evidence and phase-IV pharmacovigilance data are needed to better understand comparative safety profile of DMARDs in RA.
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Affiliation(s)
- Rouhin Sen
- Division of Clinical Immunology and Rheumatology, The University of Alabama Birmingham, Birmingham, AL, USA
- Medicine/Rheumatology Birmingham Veterans Affairs Medical Center (VAMC), Birmingham, AL, USA
| | - Maria Riofrio
- Division of Clinical Immunology and Rheumatology, The University of Alabama Birmingham, Birmingham, AL, USA
| | - Jasvinder A Singh
- Division of Clinical Immunology and Rheumatology, The University of Alabama Birmingham, Birmingham, AL, USA
- Medicine/Rheumatology Birmingham Veterans Affairs Medical Center (VAMC), Birmingham, AL, USA
- Department of Epidemiology, UAB School of Public Health, Birmingham, AL, USA
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Domínguez-Casas LC, Lasa-Teja C, Ferraz-Amaro I, Castañeda S, Blanco R. Increased Risk of Herpes Zoster in Rheumatoid Arthritis Not Only Due to JAK Inhibitors-Study of 392 Patients from Single University Center. J Clin Med 2024; 13:3121. [PMID: 38892832 PMCID: PMC11172981 DOI: 10.3390/jcm13113121] [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: 03/12/2024] [Revised: 04/08/2024] [Accepted: 05/07/2024] [Indexed: 06/21/2024] Open
Abstract
Background/Objectives: Patients with rheumatoid arthritis (RA) have an increased risk of infection. Their risk of presenting herpes zoster (HZ) is 1.5-2 times higher than immunocompetent individuals and disseminated presentation is more frequent. Our aim was to analyze the prevalence and general features of HZ in RA patients. Methods: This was a prospective study of 392 RA patients included in the vaccination program of our hospital between 2011 and 2016, and follow-up continued until December 2020. A diagnosis of HZ was made according to clinical manifestations: skin rash, blisters, paresthesia, and local pain in one or more dermatomes. Results: We studied 392 participants (309 women/83 men), mean age 59 ± 13 years. Every patient was followed-up over a mean period of 137 ± 110 months (range: 42 months-42 years). HZ infection was observed in 30 of 392 (25 women/5 men) patients, age (mean ± SD) 64.7 ± 11.8 years. Prevalence was 7.65% in this period and the incidence rate was 13.22/1000 patients/year. Three patients had facial involvement, one had optic involvement, and one patient presented disseminated HZ. Seven patients presented post herpetic neuralgia treated with gabapentinoids. The main features of RA of these 30 patients were: positive RF (n = 17; 56.6%), positive anti-CCP (n = 13; 43.3%), and erosive disease (n = 10; 33.3%). At HZ infection, the treatments were glucocorticoids (n = 19; 63.3%), conventional DMARDs (n = 15; 50%), biological DMARDs (n = 15; 50%), tofacitinib (n = 2; 6.6%), and upadacitinib (n = 1; 3.3%). Conclusions: HZ is a relatively frequent viral complication in RA patients. In our series, one patient presented disseminated HZ and nearly 25% of patients had post-herpetic neuralgia. Including a HZ vaccine in our vaccination program for RA patients may be beneficial.
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Affiliation(s)
| | - Carmen Lasa-Teja
- Rheumatology, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain;
| | - Iván Ferraz-Amaro
- Rheumatology, Hospital Universitario de Canarias, 38320 Tenerife, Spain;
| | - Santos Castañeda
- Rheumatology, Hospital Universitario de La Princesa, IIS-Princesa, 28006 Madrid, Spain;
| | - Ricardo Blanco
- Rheumatology, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain;
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Marijam A, Vroom N, Bhavsar A, Posiuniene I, Lecrenier N, Vroling H. Systematic Literature Review on the Incidence of Herpes Zoster in Populations at Increased Risk of Disease in the EU/EEA, Switzerland, and the UK. Infect Dis Ther 2024; 13:1083-1104. [PMID: 38656653 PMCID: PMC11098998 DOI: 10.1007/s40121-024-00963-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 03/15/2024] [Indexed: 04/26/2024] Open
Abstract
INTRODUCTION Older adults and patients with underlying conditions such as immunocompromised (IC) populations (e.g., due to medical conditions or immunosuppressive medication) are at increased risk for herpes zoster (HZ). The first HZ recombinant vaccine for IC patients was approved in 2020. Limited evidence exists to inform decision-makers on HZ incidence in high-risk patients in Europe. This systematic literature review (SLR) assessed HZ incidence across 14 high-risk populations in the European Union/European Economic Area, Switzerland, and the United Kingdom. METHODS An SLR (Embase, Medline, 2002-2022, observational studies) was performed to identify HZ incidence (i.e., primary outcomes: rate or cumulative; secondary: relative incidence) in type 1 and 2 diabetes mellitus (DM); chronic obstructive pulmonary disease and asthma; depression; rheumatic disorders (RD); multiple sclerosis (MS); inflammatory bowel diseases (IBD); psoriasis; lupus; human immunodeficiency virus (HIV); solid organ transplantation (SOT); solid organ malignancy (SOM); hematologic malignancy (HM); and stem cell transplantation (SCT). RESULTS Of 776 unique records screened, 59 studies were included (24 reported incidence rate per 1000 person-years; two, cumulative incidence per 1000 persons; and 33, relative incidence). The highest incidence rates were reported for SOT (12.1-78.8) and SCT (37.2-56.1); HM (2.9-32.0); RD (0.41-21.5); lupus (11.0-16.5); IC mixed population (11.3-15.5); HIV/AIDS (11.8-13.0); chronic respiratory diseases (4.7-11.4); SOM (8.8-11.0); IBD (7.0-10.8); DM (4.3-9.4); depression (7.2-7.6); MS (5.7-6.3); and psoriasis (5.3-6.1). In many high-risk populations, HZ incidence was higher for older age groups, women, and some treatments. CONCLUSIONS The HZ incidence rate in Europe increased with age and varied across high-risk populations, with high rates for solid organ and stem cell transplants, cancer, and rheumatoid arthritis. Most studies were retrospective with methodological differences affecting generalizability and comparability. Future studies should stratify data by IC population, age, sex, severity, medication, and study timeframe.
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Affiliation(s)
| | - Nikki Vroom
- Pallas Health Research & Consultancy, A P95 Company, Rotterdam, The Netherlands
| | | | | | | | - Hilde Vroling
- Pallas Health Research & Consultancy, A P95 Company, Rotterdam, The Netherlands
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Malherbe J, Godard P, Lacherade JC, Coirier V, Argaud L, Hyvernat H, Schneider F, Charpentier J, Wallet F, Pocquet J, Plantefeve G, Quenot JP, Bay P, Delbove A, Georges H, Urbina T, Schnell D, Le Moal C, Stanowski M, Muris C, Jonas M, Sauneuf B, Lesieur O, Lhermitte A, Calvet L, Gueguen I, du Cheyron D. Clinical description and outcome of overall varicella-zoster virus-related organ dysfunctions admitted in intensive care units: the VAZOREA cohort study. Ann Intensive Care 2024; 14:44. [PMID: 38548917 PMCID: PMC10978565 DOI: 10.1186/s13613-024-01270-w] [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: 12/12/2023] [Accepted: 02/23/2024] [Indexed: 04/01/2024] Open
Abstract
BACKGROUND Due to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019. RESULTS One-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p < 0.001). CONCLUSION Overall, severe VZV manifestations are associated with high mortality in the ICU, which appears to be driven by immunosuppression status rather than any specific organ involvement. Deciphering the clinical phenotypes may help clinicians identify high-risk patients and assess prognosis.
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Affiliation(s)
- Jolan Malherbe
- Normandie Univ, UNICAEN, CHU de Caen Normandie, Médecine Intensive - Réanimation, Caen, 14000, France.
| | - Pierre Godard
- Service de Médecine Intensive - Réanimation, CHU Bordeaux site Pellegrin, Bordeaux, France
| | | | - Valentin Coirier
- Service de Médecine Intensive - Réanimation, CHU de Rennes, Rennes, 35000, France
| | - Laurent Argaud
- Service de Médecine Intensive - Réanimation, Hôpital Edouard Herriot, Hospices civils de Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Est, Lyon, France
| | - Hervé Hyvernat
- Service de Médecine Intensive - Réanimation, Université Côte d'Azur (UCA), CHU de Nice, 151 route Saint Antoine de Ginestière, Nice, 06200, France
| | - Francis Schneider
- Médecine Intensive - Réanimation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg et Unistra, Strasbourg, France
| | - Julien Charpentier
- Service de Médecine Intensive - Réanimation, Centre-Université Paris Cité, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, 75014, France
| | - Florent Wallet
- Médecine Intensive - Réanimation, CHU Lyon Sud, Pierre Benite, France
- RESHAPE Research on healthcare performance, U1290, Université Claude Bernard Lyon 1, Lyon, France
| | | | | | - Jean-Pierre Quenot
- Department of Intensive Care, Burgundy University Hospital, Dijon, France
| | - Pierre Bay
- Service de Médecine Intensive - Réanimation, AP-HP Assistance Publique Hôpitaux de Paris, Hôpitaux universitaires Henri Mondor, DMU Médecine, Créteil, 94010, France
- UPEC Université Paris-Est Créteil, INSERM, Unité U955, Equipe 18, Créteil, 94010, France
| | - Agathe Delbove
- Service de réanimation polyvalente, CHBA Vannes, Vannes, France
| | - Hugues Georges
- Service de réanimation polyvalente, Centre hospitalier de Tourcoing, Tourcoing, 59200, France
| | - Tomas Urbina
- Service de Médecine Intensive - Réanimation, Hôpital Saint-Antoine, Assistance Publique- Hôpitaux de Paris, Paris, 75012, France
| | - David Schnell
- Réanimation Polyvalente et USC, CH Angoulême, Angoulême Cedex 9, Angoulême, 19959, France
| | - Charlène Le Moal
- Service Réanimation/USC, Centre Hospitalier du Mans, Le Mans, 72037, France
| | | | - Corentin Muris
- Université de Poitiers, CHU de Poitiers, Médecine intensive Réanimation, 2 rue de la miletrie, Poitiers, 86000, France
| | - Maud Jonas
- Service Médecine Intensive - Réanimation/USC, Centre hospitalier de Saint-Nazaire, Saint-Nazaire, 44600, France
| | - Bertrand Sauneuf
- Service de Réanimation polyvalente, Centre Hospitalier Public du Cotentin, Cherbourg en Cotentin, 50100, France
| | - Olivier Lesieur
- Centre Hospitalier Saint-Louis, Réanimation polyvalente, La Rochelle, 17019, France
| | - Amaury Lhermitte
- Hôpital Universitaire Félix Guyon, Réanimation polyvalente, Allée des Topazes, Saint-Denis, La Réunion, 97400, France
| | - Laure Calvet
- Service de Médecine Intensive et Réanimation, CHU de Clermont-Ferrand, Clermont- Ferrand, France
| | - Ines Gueguen
- Service de réanimation médicale, CHRU de Lille, Lille, France
| | - Damien du Cheyron
- Normandie Univ, UNICAEN, CHU de Caen Normandie, Médecine Intensive - Réanimation, Caen, 14000, France
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Sechrist SJ, Tang E, Sun Y, Arnold BF, Acharya NR. Immunosuppressive Medications and COVID-19 Outcomes in Patients with Noninfectious Uveitis in the Era of COVID-19 Vaccinations. OPHTHALMOLOGY SCIENCE 2024; 4:100411. [PMID: 38146526 PMCID: PMC10749272 DOI: 10.1016/j.xops.2023.100411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 09/30/2023] [Accepted: 10/06/2023] [Indexed: 12/27/2023]
Abstract
Purpose To determine the risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in the era of COVID-19 vaccination among patients with noninfectious uveitis (NIU) taking immunosuppressive therapies. Design Retrospective cohort study from July 1, 2021, to June 30, 2022, using data from the Optum Labs Data Warehouse (OLDW) de-identified claims database. Participants Patients with a diagnosis of NIU from January 1, 2017, and who had ≥ 1 year of continuous enrollment in the OLDW. Methods Incidence rates (IRs) were calculated for each COVID-19 outcome. Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of systemic corticosteroid (SC) exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models. Main Outcome Measures Hazard ratios and IRs for COVID-19 infection, hospitalization, and death. Results This study included 62 209 patients with NIU. A total of 12 895 (20.7%) were exposed to SCs during the risk period. Incidence rates were increased when exposed to SCs versus unexposed for all COVID-19 outcomes. Incidence rates were also increased for all COVID-19 outcomes when exposed to SCs without COVID-19 vaccination versus exposed to SCs with ≥ 1 vaccination. In adjusted models, SCs were associated with increased risk of COVID-19 infection (HR, 3.57; 95% confidence interval [CI], 3.24-3.93; P < 0.0001), hospitalization (HR, 2.75; 95% CI, 2.07-3.65; P < 0.0001), and death (HR, 2.49; 95% CI 1.29-4.82; P = 0.007). Incremental increases in SC dose were associated with a greater risk for all outcomes. Disease-modifying anti-rheumatic drugs were associated with a decreased risk of infection (HR, 0.84; 95% CI, 0.74-0.96; P = 0.01), and tumor necrosis factor-α inhibitors were associated with an increased risk of infection (HR, 1.18; 95% CI, 1.01-1.39; P = 0.04). Conclusions Systemic corticosteroid exposure continues to be associated with greater risk of COVID-19 infection, hospitalization, and death among patients with NIU in an era of widespread COVID-19 vaccination. Unvaccinated individuals who are exposed to immunosuppressive treatments have a greater risk of severe outcomes. Coronavirus disease 2019 vaccination should be strongly encouraged in these patients. Financial Disclosures Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Affiliation(s)
- Samantha J. Sechrist
- F.I. Proctor Foundation, University of California, San Francisco, California
- School of Medicine, University of California, San Francisco, California
| | - Emily Tang
- F.I. Proctor Foundation, University of California, San Francisco, California
| | - Yuwei Sun
- F.I. Proctor Foundation, University of California, San Francisco, California
| | - Benjamin F. Arnold
- F.I. Proctor Foundation, University of California, San Francisco, California
| | - Nisha R. Acharya
- F.I. Proctor Foundation, University of California, San Francisco, California
- Department of Ophthalmology, University of California, San Francisco, California
- Department of Epidemiology and Biostatistics, University of California, San Francisco, California
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Gazitt T, Hayat N, Stein N, Haddad A, Feldhamer I, Cohen AD, Saliba W, Zisman D. The Risk of Herpes Zoster Events in Patients with Spondyloarthritis and the Effect of BNT162b2 mRNA COVID-19 Vaccine. Vaccines (Basel) 2024; 12:85. [PMID: 38250898 PMCID: PMC10821079 DOI: 10.3390/vaccines12010085] [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: 11/23/2023] [Revised: 01/07/2024] [Accepted: 01/10/2024] [Indexed: 01/23/2024] Open
Abstract
The data on the risk of herpes zoster (HZ) in spondyloarthropathy (SpA) patients are sparse, especially regarding its association with the novel mRNA COVID-19 vaccines and immunosuppressants. We aimed to evaluate whether SpA diagnosis and/or immunosuppressant use affect HZ risk and the influence of mRNA COVID-19 vaccination. We assessed the association between SpA (psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) diagnoses and HZ in a large population database with patients matched by age and sex to controls. We also assessed the association between the COVID-19 vaccine and new-onset HZ using two nested case-control studies, identifying all new HZ cases diagnosed from 1 January-31 December 2021 within the SpA and general population cohorts, matched randomly by sex, age and HZ index date to controls without HZ. Exposure to mRNA COVID-19 vaccination was ascertained in the 6 weeks prior to the index date both in cases and controls. In our results, the incidence rate of HZ was higher in PsA patients vs. the general population, at 1.03 vs. 0.64 per 100 person-years, respectively (adjusted HR = 1.55; 95%CI, 1.19-2.02). Within the SpA group, Jak-I treatment was associated with a higher risk of developing new-onset HZ (adjusted OR = 3.79; 1.15-12.5). Multivariable conditional logistic regression models we used showed no association between COVID-19 vaccination and new-onset HZ among the SpA patients (OR = 1.46; 0.68-3.14).
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Affiliation(s)
- Tal Gazitt
- Rheumatology Unit, Carmel Medical Center, Haifa 3436212, Israel; (A.H.); (D.Z.)
- Division of Rheumatology, University of Washington Medical Center, Seattle, WA 98195-6428, USA
| | - Noa Hayat
- Department of Internal Medicine, Carmel Medical Center, Haifa 3436212, Israel;
| | - Nili Stein
- Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa 3436212, Israel (W.S.)
| | - Amir Haddad
- Rheumatology Unit, Carmel Medical Center, Haifa 3436212, Israel; (A.H.); (D.Z.)
| | - Ilan Feldhamer
- Chief Physician’s Office, Central Headquarters, Clalit Health Services, Tel Aviv 67754, Israel
| | - Arnon Dov Cohen
- Chief Physician’s Office, Central Headquarters, Clalit Health Services, Tel Aviv 67754, Israel
- Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
| | - Walid Saliba
- Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa 3436212, Israel (W.S.)
- The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
| | - Devy Zisman
- Rheumatology Unit, Carmel Medical Center, Haifa 3436212, Israel; (A.H.); (D.Z.)
- The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
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Kridin K, Zirpel H, Mruwat N, Ludwig RJ, Thaci D. Evaluating the risk of infections under interleukin 23 and interleukin 17 inhibitors relative to tumour necrosis factor inhibitors - A population-based study. J Eur Acad Dermatol Venereol 2023; 37:2319-2326. [PMID: 37466275 DOI: 10.1111/jdv.19328] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 06/26/2023] [Indexed: 07/20/2023]
Abstract
BACKGROUND The risk of infections among patients with psoriasis undergoing interleukin (IL)-23 inhibitors (IL-23i) and IL-17 inhibitors (IL-17i) is yet to be exhaustively determined. OBJECTIVE To assess the risk of infectious complications in patients with psoriasis managed by IL-23i and IL-17i with tumour necrosis factor inhibitors (TNFi) as a comparator. METHODS A global cohort study comprised two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL-23i (n = 5272) versus TNFi (n = 5272) and (ii) new users of IL-17i (n = 15,160) versus TNFi (n = 15,160). Study groups were compared regarding the risk of 26 different infections. Propensity score matching was conducted to optimize between-group comparability. RESULTS Patients under IL-23i had a lower risk of otitis media (HR, 0.66; 95% CI, 0.44-0.97), encephalitis (HR, 0.18; 95% CI, 0.04-0.78), herpes zoster (HZ; HR, 0.58; 95% CI, 0.41-0.82), hepatitis B virus (HBV) reactivation (HR, 0.24; 95% CI, 0.12-0.47), cytomegalovirus (HR, 0.25; 95% CI, 0.07-0.86), influenza (HR, 0.52; 95% CI, 0.38-0.71) and parasitic diseases (HR, 0.78; 95% CI, 0.64-0.95). IL-17i was associated with a decreased risk of pneumonia (HR, 0.76; 95% CI, 0.68-0.85), septicaemia (HR, 0.84; 95% CI, 0.72-0.97), upper respiratory tract infection (HR, 0.84; 95% CI, 0.77-0.92), HZ (HR, 0.79; 95% CI, 0.67-0.92), HBV (HR, 0.59; 95% CI, 0.46-0.76) and hepatitis C virus (HR, 0.71; 95% CI, 0.57-0.88) reactivation, cytomegalovirus (HR, 0.58; 95% CI, 0.36-0.93), Epstein-Barr virus (HR, 0.38; 95% CI, 0.19-0.75), influenza (HR, 0.70; 95% CI, 0.61-0.81) and parasitic diseases (HR, 0.80; 95% CI, 0.72-0.88). CONCLUSION Compared with TNFi, IL-23i and IL-17i are associated with decreased risk of several infectious diseases. These agents might be preferred in patients with susceptibility to infections.
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Affiliation(s)
- Khalaf Kridin
- Lűbeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
- Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Henner Zirpel
- Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lübeck, Germany
| | - Noor Mruwat
- Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel
| | - Ralf J Ludwig
- Lűbeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
- Department of Dermatology, University of Lübeck, Lübeck, Germany
| | - Diamant Thaci
- Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lübeck, Germany
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16
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Mataix J, García L, Belinchón I, Ruiz Carrascosa JC, de la Cueva P, Carrascosa JM. Moderate to Severe Psoriasis in Older Adults: Recommendations on Management from the Psoriasis Working Group of the Spanish Academy of Dermatology and Venereology (AEDV). ACTAS DERMO-SIFILIOGRAFICAS 2023; 114:802-811. [PMID: 37244396 DOI: 10.1016/j.ad.2023.05.016] [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: 04/25/2023] [Revised: 05/05/2023] [Accepted: 05/06/2023] [Indexed: 05/29/2023] Open
Abstract
Managing moderate to severe psoriasis in older adults is complex due to factors characteristic of the later years of life, such as associated comorbidity, polypharmacy, and immunosenescence. This consensus statement discusses 17 recommendations for managing treatment for moderate to severe psoriasis in patients older than 65 years. The recommendations were proposed by a committee of 6 dermatologists who reviewed the literature. Fifty-one members of the Psoriasis Working Group of the Spanish Academy of Dermatology and Venereology (AEDV) then applied the Delphi process in 2 rounds to reach consensus on which principles to adopt. The recommendations can help to improve management, outcomes, and prognosis for older adults with moderate to severe psoriasis.
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Affiliation(s)
- J Mataix
- Departamento de Dermatología, Hospital Marina Baixa de Villajoyosa, Alicante, España
| | - L García
- Departamento de Dermatología, Hospital Universitario San Juan, Alicante, España
| | - I Belinchón
- Departamento de Dermatología, Hospital General Universitario Dr. Balmis- ISABIAL-UMH, Alicante, España.
| | - J C Ruiz Carrascosa
- Departamento de Dermatología, Hospital Universitario Clínico San Cecilio, Granada, España
| | - P de la Cueva
- Departamento de Dermatología, Hospital Universitario Infanta Leonor, Madrid, España
| | - J M Carrascosa
- Departamento de Dermatología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, España
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17
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Mataix J, García L, Belinchón I, Ruiz Carrascosa JC, de la Cueva P, Carrascosa JM. [Translated article] Moderate to Severe Psoriasis in Older Adults: Recommendations on Management From the Psoriasis Working Group of the Spanish Academy of Dermatology and Venereology (AEDV). ACTAS DERMO-SIFILIOGRAFICAS 2023; 114:T802-T811. [PMID: 37506825 DOI: 10.1016/j.ad.2023.07.016] [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: 04/25/2023] [Accepted: 05/06/2023] [Indexed: 07/30/2023] Open
Abstract
Managing moderate to severe psoriasis in older adults is complex due to factors characteristic of the later years of life, such as associated comorbidity, polypharmacy, and immunosenescence. This consensus statement discusses 17 recommendations for managing treatment for moderate to severe psoriasis in patients older than 65 years. The recommendations were proposed by a committee of 6 dermatologists who reviewed the literature. Fifty-one members of the Psoriasis Working Group of the Spanish Academy of Dermatology and Venereology (AEDV) then applied the Delphi process in 2 rounds to reach consensus on which principles to adopt. The recommendations can help to improve management, outcomes, and prognosis for older adults with moderate to severe psoriasis.
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Affiliation(s)
- J Mataix
- Departamento de Dermatología, Hospital Marina Baixa de Villajoyosa, Alicante, Spain
| | - L García
- Departamento de Dermatología, Hospital Universitario San Juan, Alicante, Spain
| | - I Belinchón
- Departamento de Dermatología, Hospital General Universitario Dr. Balmis - ISABIAL-UMH, Alicante, Spain.
| | - J C Ruiz Carrascosa
- Departamento de Dermatología, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | - P de la Cueva
- Departamento de Dermatología, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - J M Carrascosa
- Departamento de Dermatología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
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Günbatar N, Bulduk B, Bezgin S, Oto G, Bayıroğlu F, Bulduk M. The Effect of Moderate-Intensity Physical Exercise on Some Serum Inflammation Markers and the Immune System in Rats Fed Intermittent Fasting with a High-Fat Diet. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1687. [PMID: 37763806 PMCID: PMC10537032 DOI: 10.3390/medicina59091687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 09/15/2023] [Accepted: 09/17/2023] [Indexed: 09/29/2023]
Abstract
Background and Objectives: This study aimed to investigate the impact of moderate-intensity physical exercise on serum inflammation markers and the immune system in rats that were fed a high-fat diet (HFD) with intermittent fasting. Materials and Methods: A total of 48 Wistar albino male rats were included in the study and divided into eight groups, each consisting of six rats. Group 1 served as the control group (CG), receiving a standard diet. Group 2 followed the standard nutrition program with intermittent fasting (CG + IF). Group 3 underwent exercise with a standard diet (CG + E). Group 4 underwent both a standard diet with intermittent fasting and exercise (CG + IF + E). Group 5 was fed a high-fat diet (HFD). Group 6 received a high-fat diet with intermittent fasting (HFD + IF). Group 7 followed a high-fat diet with exercise (HFD + E). Group 8 underwent both a high-fat diet with intermittent fasting and exercise (HFD + IF + E). The study lasted for 8 weeks. Results: The results of the analysis show that lymphocyte cell levels in groups HFD + IF, HFD + IF, and HFD + IF + E were higher compared to groups CG-HFD (p < 0.05). Additionally, B lymphocyte and monocyte cell levels were higher in group HFD + IF + E compared to groups CG, CG + IF, and CG + IF + E, as well as CG, CG + IF, and CG + E, respectively. TNF-α levels were significantly higher in group HFD compared to the other groups. Furthermore, IL 10 levels were higher in group HFD + IF + E compared to the other groups. Conclusions: These findings indicate that moderate exercise and intermittent fasting, particularly in groups fed a high-fat diet, increased anti-inflammatory cytokine levels, and certain immune system cell counts, while decreasing pro-inflammatory cytokine levels.
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Affiliation(s)
- Nizamettin Günbatar
- Van School of Health, Van YuzuncuYıl University, 65090 Van, Turkey; (B.B.); (S.B.); (M.B.)
| | - Bahattin Bulduk
- Van School of Health, Van YuzuncuYıl University, 65090 Van, Turkey; (B.B.); (S.B.); (M.B.)
| | - Selver Bezgin
- Van School of Health, Van YuzuncuYıl University, 65090 Van, Turkey; (B.B.); (S.B.); (M.B.)
| | - Gökhan Oto
- Department of Pharmacology, Van YuzuncuYıl University, 65090 Van, Turkey;
| | - Fahri Bayıroğlu
- Faculty of Medicine, Department of Physiology, Yıldırım Beyazıt University, 06200 Ankara, Turkey;
| | - Mehmet Bulduk
- Van School of Health, Van YuzuncuYıl University, 65090 Van, Turkey; (B.B.); (S.B.); (M.B.)
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Bonfiglioli KR, de Medeiros Ribeiro AC, Carnieletto AP, Pereira I, Domiciano DS, da Silva HC, Pugliesi A, Pereira LR, Guimarães MFR, Giorgi RDN, Reis APMG, Brenol CV, Louzada-Júnior P, da Cunha Sauma MDFL, Radominski SC, da Mota LMH, da Rocha Castelar-Pinheiro G. Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort. Adv Rheumatol 2023; 63:34. [PMID: 37496102 DOI: 10.1186/s42358-023-00318-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 07/19/2023] [Indexed: 07/28/2023] Open
Abstract
INTRODUCTION Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. OBJECTIVE To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. METHOD Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann-Whitney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). RESULTS 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) ('p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. CONCLUSIONS ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.
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Affiliation(s)
- Karina Rossi Bonfiglioli
- Serviço de Reumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), Av.Dr. Arnaldo, 455 - 3º andar - Reumatologia, São Paulo, SP, 01246-903, Brazil.
| | - Ana Cristina de Medeiros Ribeiro
- Serviço de Reumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), Av.Dr. Arnaldo, 455 - 3º andar - Reumatologia, São Paulo, SP, 01246-903, Brazil
| | | | - Ivânio Pereira
- Serviço de Reumatologia do Hospital Universitário da Universidade Federal de Santa Catarina (UFSC), Florianópolis, Brazil
| | - Diogo Souza Domiciano
- Serviço de Reumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), Av.Dr. Arnaldo, 455 - 3º andar - Reumatologia, São Paulo, SP, 01246-903, Brazil
| | - Henrique Carriço da Silva
- Serviço de Reumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), Av.Dr. Arnaldo, 455 - 3º andar - Reumatologia, São Paulo, SP, 01246-903, Brazil
| | - Alisson Pugliesi
- Disciplina de Reumatologia da Faculdade de Ciências Médicas da Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
| | - Leticia Rocha Pereira
- Serviço de Reumatologia da Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | | | - Rina Dalva Neubarth Giorgi
- Serviço de Reumatologia do Hospital do Servidor Público Estadual de São Paulo (HSPE-IAMSPE), São Paulo, Brazil
| | | | - Claiton Viegas Brenol
- Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (HCPA/UFRGS), Porto Alegre, Brazil
| | - Paulo Louzada-Júnior
- Disciplina de Reumatologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP-RP), São Paulo, Brazil
| | | | - Sebastião Cezar Radominski
- Disciplina de Reumatologia, Faculdade de Medicina da Universidade Federal do Paraná (UFPR), Curitiba, Brazil
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20
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Atzeni F, Gozza F, Riva A, Alciati A, Galloway J. Conventional, biological disease-modifying anti-rheumatic drugs and Janus kinase inhibitors and varicella zoster virus. Expert Opin Pharmacother 2023; 24:679-689. [PMID: 36946287 DOI: 10.1080/14656566.2023.2195050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2023]
Abstract
INTRODUCTION The advent of biological disease-modifying anti-rheumatic drugs (bDMARDs), and more recently of Janus kinase inhibitors (JAKi), has had a major impact on the herpes zoster (HZ) reactivation, which represents an important clinical challenge in the treatment of inflammatory arthritis (IA) in patients with a complete pharmacological control of peripheral inflammation. AREAS COVERED In this review, we provide an overview on the effects of conventional DMARDs/ bDMARDs and JAKi on HZ reactivation. Furthermore, we underline the controversial findings and the potential management strategies. We searched PubMed, Medline, and the Cochrane Library for papers published between 1995 and February 2017. EXPERT OPINION The overall data showed a slightly higher risk of HZ in patients treated with bDMARDs, and more pronounced for those treated with JAKi. As management strategies, we suggest an effective vaccination campaign and a focus on early diagnosis.
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Affiliation(s)
- Fabiola Atzeni
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy
| | - Francesco Gozza
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy
| | - Agostino Riva
- Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy
- III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy
| | - Alessandra Alciati
- Department of Clinical Neurosciences, Villa S. Benedetto Menni, Albese (Como), Italy
- Humanitas Clinical and Research Center, Rozzano, Italy
| | - James Galloway
- Centre for Rheumatic Diseases, King's College London, London, UK
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21
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Gialouri CG, Moustafa S, Thomas K, Hadziyannis E, Vassilopoulos D. Herpes zoster in patients with inflammatory arthritides or ulcerative colitis treated with tofacitinib, baricitinib or upadacitinib: a systematic review of clinical trials and real-world studies. Rheumatol Int 2023; 43:421-435. [PMID: 36635577 PMCID: PMC9968274 DOI: 10.1007/s00296-022-05270-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 12/29/2022] [Indexed: 01/14/2023]
Abstract
JAK inhibitors (JAKi) are new targeted-synthetic drugs, approved for various immune-mediated inflammatory diseases (IMIDs), including inflammatory arthritides (rheumatoid arthritis-RA, psoriatic arthritis-PsA, ankylosing spondylitis-AS) and ulcerative colitis (UC). JAKi have been associated with increased risk for herpes zoster (HZ), but the relative risk among different JAKi in these IMIDs remains unclear. We aimed to systematically review the incidence of HZ among RA, PsA, AS and UC patients treated with the approved doses of tofacitinib (TOFA), baricitinib (BARI) or upadacitinib (UPA). PubMed, Embase, Scopus, Cochrane and Web-of-Science were searched up to 30 March 2022. Clinical trials and real-world studies (RWS) were included. Outcomes assessed were the incidence rate (/100 patient-years) or/and cumulative incidence of HZ. From 1710 records, 53 clinical trials and 25 RWS were included (RA: 54, PsA: 8, AS: 4, and UC: 12). In clinical trials, the HZ-incidence was higher in TOFA-treated patients with RA (2.2-7.1/100 patient-years) or UC (1.3-7.6/100 patient-years) compared to PsA (1.7/100 patient-years), and with higher doses of TOFA in UC (10 mg/twice daily: 3.2-7.6/100 patient-years vs. 5 mg/twice daily: 1.3-2.3/100 patient-years). Evidence for HZ-risk in JAKi-treated patients with AS and in UPA-treated patients was limited. The HZ-incidence between TOFA and BARI groups in 2 RA RWS did not differ significantly. Concomitant glucocorticoid, but not methotrexate, use in RA increased the HZ-risk. This systematic review showed higher HZ-risk in RA or UC than PsA patients treated with TOFA, in those treated with higher TOFA doses or with concomitant glucocorticoids. Preventive measures and monitoring of JAKi-treated patients with IMIDs are essential in daily practice.
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Affiliation(s)
- Chrysoula G Gialouri
- Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, General Hospital of Athens "Hippokration", Athens, Greece
| | - Savvina Moustafa
- Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, General Hospital of Athens "Hippokration", Athens, Greece
| | - Konstantinos Thomas
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens School of Medicine, Attikon University General Hospital, Chaidari, Greece
| | - Emilia Hadziyannis
- Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, General Hospital of Athens "Hippokration", Athens, Greece
| | - Dimitrios Vassilopoulos
- Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, General Hospital of Athens "Hippokration", Athens, Greece.
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22
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Dlamini ST, Htet KM, Theint ECC, Mayadilanuari AM, Li WM, Tung YC, Tu HP. Herpes Zoster Risk in Patients with Rheumatoid Arthritis and Its Association with Medications Used. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:2123. [PMID: 36767490 PMCID: PMC9915285 DOI: 10.3390/ijerph20032123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 01/19/2023] [Accepted: 01/20/2023] [Indexed: 06/18/2023]
Abstract
Rheumatoid arthritis (RA) was associated with the risk of incident herpes zoster (HZ), which might be influenced by medication use by RA patients. We aimed to investigate the association of RA with the risk of incident HZ and how the HZ risk effected by RA medications in CIC RA patients. We conducted an observational study including population-based representative insurance claims data of 19,673 patients with RA and 39,346 matched patients without RA during 1997-2010 from the Taiwan National Health Insurance Research Database; we identified 1651 patients with catastrophic illness-certified (CIC) RA and 11,557 matched patients with non-CIC RA. Exploratory analyses assessed the association between RA/CIC RA and risk of incident HZ and its complications. The association of prescribed medications with HZ risk in CIC RA patients was also estimated. The incidence rates of HZ were higher in CIC RA patients and non-CIC RA than in the matched people without RA (21.95 and 14.03 vs. 7.36 events per 1000 person-years, respectively). The adjusted incidence rate ratio (95% confidence interval (CI)) for HZ was 1.74 (1.65-1.84) in RA patients vs. matched non-RA and 1.65 (1.44-1.89) in CIC RA patients vs. non-CIC RA. For HZ complications, RA had a 2.85-fold higher risk than non-RA, and CIC RA had a 1.78-fold higher risk than non-CIC RA. Moreover, in CIC RA patients, prednisolone use was associated with incident HZ risk compared with prednisolone nonuse (adjusted odds ratio 1.48, 1.08-2.03); prolonged prednisolone use (approximately 5 years) increased the risk (adjusted odds ratio 2.16, 1.46-3.19). Our results suggested that RA was positively associated with HZ risk, particularly in RA patients with prednisolone use.
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Affiliation(s)
| | - Kyaw Moe Htet
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Ei Chue Chue Theint
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | | | - Wei-Ming Li
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan
- Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Department of Urology, Ministry of Health and Welfare, Pingtung Hospital, Pingtung 90054, Taiwan
| | - Yi-Ching Tung
- Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Hung-Pin Tu
- Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan
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23
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Rezahosseini O, Liljendahl MS, Loft N, Møller DL, Harboe ZB, Rasmussen MK, Ajgeiy KK, Egeberg A, Skov L, Nielsen SD. Incidence, risk factors, and consequences of human alphaherpesvirus infections in patients with psoriasis who initiate methotrexate or biologic agents. J Infect Dis 2022; 226:1510-1518. [PMID: 36097341 DOI: 10.1093/infdis/jiac367] [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: 06/15/2022] [Accepted: 09/09/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Immunosuppressive agents may increase the risk of infections with human alphaherpesviruses. METHODS We included all adult patients with moderate to severe psoriasis who initiated methotrexate (MTX) or biologic agents in a retrospective cohort study. An episode of alphaherpesviruses infection was defined as filling a prescription for systemic acyclovir, valacyclovir, or famciclovir. Using nation-wide registries, we determined the incidence, risk factors, 180-days hospital contacts, and 30-days mortality following infection. RESULTS We included 7,294 patients; 4,978 (68%) received MTX, and 2,316 (32%) biologic agents. The incidence rates [95% CI] of alphaherpesviruses were 23 [20-27], 26 [19-35], 17 [11-27] and 6.7 [1.3-21] per 1000 PYFU in patients on MTX, TNFα-, IL-12/23-, and IL-17 inhibitors, respectively. Males had an unadjusted HR of 0.47 (P < 0.001) for alphaherpesvirus infection. Patients on IL-17 inhibitors had an adjusted HR of 0.24 (P = 0.048) compared to TNFα inhibitors. Within 180-days after infection, 13%, 7.5%, and <0.5% of patients on MTX, TNFα inhibitors, and IL-12/23 or IL-17 inhibitors, respectively, had hospital contacts, and the 30-days mortality for all groups was <0.5%. CONCLUSIONS The incidence and risk of alphaherpesvirus infections was comparable between patients on MTX and TNFα inhibitors, while use of IL-17 inhibitors was associated with a lower risk.
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Affiliation(s)
- Omid Rezahosseini
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Mie Sylow Liljendahl
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, .,Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark
| | - Nikolai Loft
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen,
| | - Dina Leth Møller
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen,
| | - Zitta Barrella Harboe
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, .,Department of Pulmonary and Infectious Diseases, Hospital of Nordsjælland, Nordsjællands University Hospital, Denmark
| | | | - Kawa Khaled Ajgeiy
- DERMBIO, .,Department of Dermatology, Odense University Hospital, Odense, Denmark
| | - Alexander Egeberg
- Department of Dermatology, Bispebjerg Hospital, Copenhagen, .,DERMBIO, Denmark
| | - Lone Skov
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, .,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.,DERMBIO, Denmark
| | - Susanne Dam Nielsen
- Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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24
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Lactic Acid Regulation: A Potential Therapeutic Option in Rheumatoid Arthritis. J Immunol Res 2022; 2022:2280973. [PMID: 36061305 PMCID: PMC9433259 DOI: 10.1155/2022/2280973] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 08/16/2022] [Indexed: 11/29/2022] Open
Abstract
Rheumatoid arthritis (RA) is a chronic, persistent autoimmune disease that causes severe joint tissue damage and irreversible disability. Cumulative evidence suggests that patients suffering from RA for long durations are at risk of functional damage to cardiovascular, kidney, lung, and other tissues. This seriously affects the quality of work and life of patients. To date, no clear etiology of RA has been found. Recent studies have revealed that the massive proliferation of synoviocytes and immune cells requires a large amount of energy supply. Rapid energy supply depends on the anaerobic glucose metabolic pathway in both RA animal models and clinical patients. Anaerobic glycolysis can increase intracellular lactic acid (LA) content. LA induces the overexpression of monocarboxylate transporters (MCTs) in cell membranes. MCTs rapidly transport LA from the intracellular to the intercellular or articular cavity. Hence, a relatively high accumulation of LA could be formed in the intercellular and articular cavities of inflammatory joints. Moreover, LA contributes to the migration and activation of immune cells. Immune cells proliferate and secrete interleukins (IL) including IL-1, IL-2, IL-13, IL-17, and other inflammatory factors. These inflammatory factors enhance the immune inflammatory response of the body and aggravate the condition of RA patients. In this paper, the effects of LA on RA pathogenesis will be summarized from the perspective of the production, transport, and metabolism of synoviocytes and immune cells. Additionally, the drugs involved in the production, transport, and metabolism of LA are highlighted.
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25
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Jeong S, Choi S, Park SM, Kim J, Ghang B, Lee EY. Incident and recurrent herpes zoster for first-line bDMARD and tsDMARD users in seropositive rheumatoid arthritis patients: a nationwide cohort study. Arthritis Res Ther 2022; 24:180. [PMID: 35902964 PMCID: PMC9330646 DOI: 10.1186/s13075-022-02871-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Accepted: 07/20/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND There is limited information regarding disease-modifying antirheumatic drug (DMARD)-dependent risks of overall, incident, and recurrent herpes zoster (HZ) during first-line biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) treatment among patients with seropositive rheumatoid arthritis (RA) in terms of HZ risk. METHODS A total of 11,720 patients with seropositive RA who were prescribed bDMARD or tofacitinib between January 2011 and January 2019 from the Korean Health Insurance Review & Assessment Service database were studied. A multivariate Cox proportional hazards regression model was adopted to evaluate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the risk of HZ dependent on the choice of first-line bDMARDs or tsDMARD, including etanercept, infliximab, adalimumab, golimumab, tocilizumab, rituximab, tofacitinib, and abatacept. RESULTS During the 34,702 person-years of follow-up, 1686 cases (14.4%) of HZ were identified, including 1372 (11.7%) incident and 314 (2.7%) recurrent HZs. Compared with that of the abatacept group, tofacitinib increased the overall risk (aHR, 2.46; 95% CI, 1.61-3.76; P<0.001), incidence (aHR, 1.99; 95% CI, 1.18-3.37; P=0.011), and recurrence (aHR, 3.69; 95% CI, 1.77-7.69; P<0.001) of HZ. Infliximab (aHR, 1.36; 95% CI, 1.06-1.74; P=0.017) and adalimumab (aHR, 1.29; 95% CI, 1.02-1.64; P=0.032) also increased the overall HZ risk. Moreover, a history of HZ was found to be an independent risk factor for HZ (aHR, 1.54; 95% CI, 1.33-1.78; P<0.001). CONCLUSIONS HZ risk is significantly increased in RA patients with a history of HZ after the initiation of bDMARDs or tsDMARD. The risk of incident and recurrent HZ was higher after tofacitinib treatment in patients with RA than that after treatment with bDMARDs. Individualized characteristics and history of HZ should be considered when selecting bDMARDs or tsDMARD for RA patients considering HZ risks.
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Affiliation(s)
- Seogsong Jeong
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.,Department of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, South Korea
| | - Seulggie Choi
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Sang Min Park
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.,Department of Family Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Jinseok Kim
- Division of Rheumatology, Department of Internal Medicine, Jeju National University School of Medicine, Jeju National University Hospital, Jeju, South Korea
| | - Byeongzu Ghang
- Division of Rheumatology, Department of Internal Medicine, Jeju National University School of Medicine, Jeju National University Hospital, Jeju, South Korea.
| | - Eun Young Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, South Korea. .,Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea.
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26
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Chiu HY, Hung YT, Huang SW, Huang YH. Comparative risk of herpes zoster in patients with psoriatic disease on systemic treatments: a systematic review and network meta-analysis. Ther Adv Chronic Dis 2022; 13:20406223221091188. [PMID: 35519434 PMCID: PMC9066628 DOI: 10.1177/20406223221091188] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 03/15/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Numerous previous studies have examined risk of herpes zoster (HZ) in psoriatic disease; however, the results of these studies are conflicting and the relative risks associated with different treatments remain largely unknown. In this meta-analysis, we examined the relative risk of HZ associated with systemic treatments for psoriatic disease. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched to identify relevant English-language studies published up to April 2021. Data were extracted using a standardized data extraction form. Network meta-analyses (NMA) was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We examined the differences in HZ risk (incidence rate ratio; IRR) between treatments using a random-effects model for direct pairwise comparisons and NMA. The surface under the cumulative ranking area was calculated to rank the HZ risk for each treatment condition. Results: This study analyzed 13 studies including 19 treatment arms involving a total of 443,104 patients with psoriatic disease. Corticosteroids (CS) [IRR, 2.56; 95% confidence interval (CI), 1.59–4.13], a Janus kinase inhibitor (JAKi; tofacitinib) (IRR, 2.34; 95% CI, 1.03–5.32), infliximab (IRR, 2.32; 95% CI, 1.27–4.21), conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) + CS (IRR, 2.26; 95% CI, 1.23–4.17), anti-tumor necrosis factor-α (anti-TNF-α) + csDMARDs and/or CS (IRR, 2.13; 95% CI, 1.38–3.31), csDMARDs (IRR, 1.62; 95% CI, 1.18–2.22), and anti-TNF-α except infliximab (IRR, 1.61; 95% CI, 1.13–2.30) were all associated with a significantly higher HZ risk compared to controls. CS treatment possessed the highest HZ risk, followed by infliximab and JAKi (tofacitinib). Phosphodiesterase-4 inhibitor, anti-interleukin-17, -23 or -12/23, phototherapy, and acitretin showed a risk similar to controls without significant differences. Conclusion: The NMA demonstrated CS, infliximab, and JAKi (tofacitinib), and several combination treatments were associated with higher HZ risk in patients with psoriasis and psoriatic arthritis. Differences in HZ risk should be taken into consideration when considering optimal psoriasis treatment.
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Affiliation(s)
- Hsien-Yi Chiu
- Department of Dermatology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu
- Department of Dermatology, National Taiwan University Hospital, Taipei
- Department of Dermatology, College of Medicine, National Taiwan University, Taipei
- Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu
| | - Yi-Teng Hung
- Department of Dermatology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan
| | - Shi-Wei Huang
- Department of Urology, National Taiwan University Hospital Yunlin Branch, Douliu
| | - Yu-Huei Huang
- Department of Dermatology, Chang Gung Memorial Hospital Linkou Branch, No.5, Fuxing St., Guishan Dist., Taoyuan City 333
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan
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27
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Ma S, Gu S, Zhang J, Qi W, Lin Z, Zhai W, Zhan J, Li Q, Cai Y, Lu Y. Robust drug bioavailability and safety for rheumatoid arthritis therapy using D-amino acids-based supramolecular hydrogels. Mater Today Bio 2022; 15:100296. [PMID: 35665233 PMCID: PMC9157599 DOI: 10.1016/j.mtbio.2022.100296] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 05/12/2022] [Accepted: 05/14/2022] [Indexed: 01/13/2023]
Affiliation(s)
- Shaodan Ma
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Diseases, Guangzhou, 510280, China
- Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, 516600, China
| | - Shunan Gu
- Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Jinwei Zhang
- Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Weizhong Qi
- Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Zhaowei Lin
- Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Weicheng Zhai
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Diseases, Guangzhou, 510280, China
| | - Jie Zhan
- Department of Laboratory Medicine, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Qi Li
- Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
- Corresponding author.
| | - Yanbin Cai
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Diseases, Guangzhou, 510280, China
- Corresponding author.
| | - Yao Lu
- Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
- Guangdong Key Lab of Orthopedic Technology and Implant, Guangzhou, 510010, China
- Corresponding author. Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
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Shin A, Lee JH, You-Jung H, Lee YJ, Lee EB, Kang EH. Infectious risk of add-on leflunomide or tacrolimus versus TNF inhibitors among patients with rheumatoid arthritis receiving background methotrexate: a population-based cohort study. Semin Arthritis Rheum 2022; 55:152019. [DOI: 10.1016/j.semarthrit.2022.152019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 03/09/2022] [Accepted: 04/25/2022] [Indexed: 10/18/2022]
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29
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Wu J, Wang K, Liu Q, Li Y, Huang Y, Liu Y, Cai J, Yin C, Li X, Yu H, Meng W, Wang H, Lu A, Li Y, Guan D. An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis. Front Pharmacol 2022; 13:801350. [PMID: 35281924 PMCID: PMC8905663 DOI: 10.3389/fphar.2022.801350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 01/04/2022] [Indexed: 12/17/2022] Open
Abstract
As a systemic inflammatory arthritis disease, rheumatoid arthritis (RA) is complex and hereditary. Traditional Chinese medicine (TCM) has evident advantages in treating complex diseases, and a variety of TCM formulas have been reported that have effective treatment on RA. Clinical and pharmacological studies showed that Ermiao Powder, which consists of Phellodendron amurense Rupr. (PAR) and Atractylodes lancea (Thunb.) DC. (ALD), can be used in the treatment of RA. Currently, most studies focus on the anti-inflammatory mechanism of PAR and ALD and are less focused on their coordinated molecular mechanism. In this research, we established an integrative pharmacological strategy to explore the coordinated molecular mechanism of the two herbs of Ermiao Powder in treating RA. To explore the potential coordinated mechanism of PAR and ALD, we firstly developed a novel mathematical model to calculate the contribution score of 126 active components and 85 active components, which contributed 90% of the total contribution scores that were retained to construct the coordinated functional space. Then, the knapsack algorithm was applied to identify the core coordinated functional components from the 85 active components. Finally, we obtained the potential coordinated functional components group (CFCG) with 37 components, including wogonin, paeonol, ethyl caffeate, and magnoflorine. Also, functional enrichment analysis was performed on the targets of CFCG to explore the potential coordinated molecular mechanisms of PAR and ALD. The results indicated that the CFCG could treat RA by coordinated targeting to the genes involved in immunity and inflammation-related signal pathways, such as phosphatidylinositol 3‑kinase/protein kinase B signaling pathway, mitogen-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, and nuclear factor-kappa B signaling pathway. The docking and in vitro experiments were used to predict the affinity and validate the effect of CFCG and further confirm the reliability of our method. Our integrative pharmacological strategy, including CFCG identification and verification, can provide the methodological references for exploring the coordinated mechanism of TCM in treating complex diseases and contribute to improving our understanding of the coordinated mechanism.
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Affiliation(s)
- Jie Wu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
| | - Kexin Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Neurosurgery Institute, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Qinwen Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
| | - Yi Li
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yingying Huang
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yujie Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
| | - Jieqi Cai
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
| | - Chuanhui Yin
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
| | - Xiaowei Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
| | - Hailang Yu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
| | - Wei Meng
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
| | - Handuo Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
| | - Aiping Lu
- Institute of Integrated Bioinformedicine and Translational Science, Hong Kong Baptist University, Hong Kong, China
- Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou, China
| | - Yazi Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
| | - Daogang Guan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China
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Incidence of complications of herpes zoster in individuals on immunosuppressive therapy: A register-based population study. J Infect 2022; 84:531-536. [PMID: 35016899 DOI: 10.1016/j.jinf.2022.01.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 01/04/2022] [Indexed: 11/22/2022]
Abstract
OBJECTIVES Herpes zoster (HZ) exposes to alterations of the quality-of-life. HZ is more frequent in immunocompromised individuals, but whether immunosuppression is associated with a higher rate of complications is not well documented. We aimed to assess association between drug-induced immunosuppression and HZ complications. METHODS Data from a sample of the French healthcare claims from 01/01/2006 to 12/31/2018 were analyzed. Complicated zoster (CZ) was defined as a hospitalization with a code for HZ or the first-time dispensation of high-dose valacyclovir and specific neuralgia analgesics. Drug-induced immunosuppression was identified through medication dispensation. Risk ratios were calculated to compare incidences in exposed individuals (EI) and non-exposed to immunosuppressive therapy (NEI). RESULTS We identified 227 and 2838 CZ, accounting for an incidence of 178 per 100,000 person-year (95%CI[154.9-201.1]) and 51.7 per 100,000 person-year (95%CI[49.8-53.6]), in EI and NEI, respectively (risk ratio: 3.44 (95%CI[3.01-3.94]). Mean age was 66 years in both groups. CZ occurred after a median of 11.7 months (IQR[5.3-49.9]) of immunosuppressive therapy. Post-herpetic neuralgia (PHN) lasted at least 3 months in 32.6% and 22.5% of cases in EI and NEI, respectively (p=.01). CONCLUSIONS Drug-induced immunosuppression increases the risk of CZ and exposes to longer-lasting PHN. Figures provided in this study could help guide prophylaxis of HZ.
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Redeker I, Albrecht K, Kekow J, Burmester GR, Braun J, Schäfer M, Zink A, Strangfeld A. Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register. Ann Rheum Dis 2022; 81:41-47. [PMID: 34321218 PMCID: PMC8762036 DOI: 10.1136/annrheumdis-2021-220651] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 07/05/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To compare event and incidence rates of herpes zoster (HZ), also known as shingles, in patients with rheumatoid arthritis under treatment with conventional synthetic (cs), targeted synthetic (ts) or biologic (b) disease-modifying antirheumatic drugs (DMARDs). METHODS Patients were prospectively enrolled from 2007 until October 2020. Reported HZ events were assigned to ongoing treatments or those terminated within 1 month prior to the HZ event. Exposure-adjusted event rates (EAERs) of HZ were calculated per 1000 patient years (py) and adjusted HRs with 95% CIs computed. Inverse probability weights (IPW) were used to adjust for confounding by indication. RESULTS Data of 13 991 patients (62 958 py) were analysed, with 559 HZ events reported in 533 patients. The EAER of HZ was highest for tsDMARDs (21.5, 95% CI 16.4 to 27.9), followed by B cell targeted therapy (10.3, 95% CI 8.0 to 13.0), monoclonal antitumour necrosis factor (anti-TNF) antibodies (9.3, 95% CI 7.7 to 11.2), interleukin 6 inhibitors (8.8, 95% CI 6.9 to 11.0), soluble TNF receptor fusion protein (8.6, 95% CI 6.8 to 10.8), T cell costimulation modulator (8.4, 95% CI 5.9 to 11.8) and csDMARDs (7.1, 95% CI 6.0 to 8.3). Adjusted for age, sex and glucocorticoids and weighted with IPW, tsDMARDs (HR 3.66, 95% CI 2.38 to 5.63), monoclonal anti-TNF antibodies (HR 1.63, 95% CI 1.17 to 2.28) and B cell targeted therapy (HR 1.57, 95% CI 1.03 to 2.40) showed a significantly higher risk compared with csDMARDs. CONCLUSION Our results provide evidence for a 3.6-fold increased risk of HZ associated with tsDMARDs and an increased risk of HZ under bDMARDs compared with csDMARDs.
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Grants
- RABBIT is supported by a joint, unconditional grant from AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Hexal, Lilly, MSD, Viatris, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis and UCB
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Affiliation(s)
- Imke Redeker
- Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
| | - Katinka Albrecht
- Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
| | - Joern Kekow
- Clinic of Rheumatology and Orthopaedics, Helios Clinic for Rheumatolog, Vogelsang-Gommern, Germany
| | | | | | - Martin Schäfer
- Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
| | - Angela Zink
- Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
| | - Anja Strangfeld
- Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
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Kwan A, Rayes HA, Lazova T, Anderson N, Bonilla D, Su J, Touma Z. Herpes zoster in SLE: prevalence, incidence and risk factors. Lupus Sci Med 2022; 9:9/1/e000574. [PMID: 35017186 PMCID: PMC8753438 DOI: 10.1136/lupus-2021-000574] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 12/16/2021] [Indexed: 11/08/2022]
Abstract
Objectives This study aimed to evaluate the prevalence and incidence of herpes zoster (HZ) events and describe its associated factors in a study of patients with SLE. Methods 491 consecutive SLE participants were screened for HZ events using a patient-reported questionnaire to capture outcomes on pain and other characteristics associated with HZ events. Sociodemographic, clinical and laboratory measures were also analysed, and time-dependent Cox regression survival analyses were performed to investigate factors associated with HZ events. Results Prevalence of HZ was 30.5%, incidence was 14.3 cases per 1000 person-years. Lymphopenia and glucocorticoid dosing were significantly associated with HZ events. Conclusions HZ is highly prevalent in SLE, which may be linked to disease-related and treatment-related effects on cellular immunity. Our results suggest that the presence of certain risk factors may be useful to allow identification of patients at risk of HZ and improve its management in patients with SLE.
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Affiliation(s)
- Andrew Kwan
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Hanan Al Rayes
- Department of Medicine, Prince Sultan Military Medical City, Riyadh, Riyadh, Saudi Arabia
| | - Tijana Lazova
- Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
| | - Nicole Anderson
- Centre for Prognosis Studies in the Rheumatic Diseases, University Health Network, Toronto, Ontario, Canada
| | - Dennisse Bonilla
- Centre for Prognosis Studies in the Rheumatic Diseases, University Health Network, Toronto, Ontario, Canada
| | - Jiandong Su
- Centre for Prognosis Studies in the Rheumatic Diseases, University Health Network, Toronto, Ontario, Canada
| | - Zahi Touma
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada .,Department of Medicine, Division of Rheumatology, University Health Network, Toronto, Ontario, Canada
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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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[Latest findings from the RABBIT register]. Z Rheumatol 2021; 81:100-109. [PMID: 34940891 PMCID: PMC8696252 DOI: 10.1007/s00393-021-01139-4] [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] [Accepted: 11/01/2021] [Indexed: 11/28/2022]
Abstract
Seit 2001 rekrutieren Rheumatolog:innen deutschlandweit Patient:innen mit rheumatoider Arthritis in das Biologikaregister RABBIT, um die Langzeitsicherheit und -wirksamkeit moderner antirheumatischer Therapien zu untersuchen. In den vergangenen 20 Jahren wurden mehr als 20.000 Patient:innen in die prospektive Kohortenstudie eingeschlossen. In diesem Beitrag fassen wir aktuelle Forschungsergebnisse der Jahre 2020 und 2021 zusammen; dabei stehen Sicherheitsaspekte, Einflussfaktoren auf die Therapiewirksamkeit und patientenberichtete Outcomes im Fokus. Mit Herpes zoster, Fazialisparese und Psoriasis wurden verschiedene unerwünschte Ereignisse untersucht, die entweder als Sicherheitssignal aus klinischen Studien oder durch die EudraVigilance-Datenbank gemeldet wurden oder als paradoxe Reaktion unter medikamentöser Behandlung aufgetreten sind. Für diese Ereignisse wurde der Einfluss der biologischen DMARD(„disease-modifying antirheumatic drug“)-Therapie analysiert. In der Publikation zu Herpes zoster berücksichtigten wir auch die medikamentöse Behandlung mit Januskinaseinhibitoren. Starkes Übergewicht kann den Erfolg einer Therapie beeinflussen. Hier gibt es geschlechtsspezifische Unterschiede, und auch das Wirkprinzip einer Therapie entscheidet, ob eine Adipositas das Therapieansprechen reduziert. Die Mehrheit der in RABBIT beobachteten Patient:innen ist nach 1 Jahr Behandlung mit der erhaltenen Therapie zufrieden. Wir konnten zeigen, welche Faktoren die Zufriedenheit mit der Wirksamkeit und der Sicherheit der Behandlung begünstigen oder aber negativ beeinflussen. Diese Übersichtsarbeit zeigt, dass Langzeitbeobachtungsstudien wie das RABBIT-Register auch nach 2 Dekaden der Datenerhebung zum Verständnis von Therapierisiken beiträgt sowie Faktoren identifiziert, die die Wirkung der Therapien beeinflussen können.
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Dai C, Jiang M, Huang YH. Anti-TNF Therapy and the Risk of Herpes Zoster Among Patients With Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:e156. [PMID: 34259845 DOI: 10.1093/ibd/izab178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Cong Dai
- Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China
| | - Min Jiang
- Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China
| | - Yu-Hong Huang
- Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China
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Curtis JR, Cofield SS, Bridges SL, Bassler J, Deodhar A, Ford TL, Huffstutter J, Jankeel A, Kivitz A, Kamal S, Lindsey S, Messaoudi I, Mendoza N, Michaud K, Mikuls TR, Ridley D, Shergy W, Siegel SAR, Winthrop KL. The Safety and Immunologic Effectiveness of the Live Varicella-Zoster Vaccine in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy : A Randomized Controlled Trial. Ann Intern Med 2021; 174:1510-1518. [PMID: 34570596 DOI: 10.7326/m20-6928] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis). OBJECTIVE To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis. DESIGN Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341). SETTING Academic and community-based rheumatology, gastroenterology, and dermatology practices. PATIENTS Adults aged 50 years or older receiving TNFis for any indication. INTERVENTION Random assignment to ZVL versus placebo. MEASUREMENTS Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid. RESULTS Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL (n = 310) or placebo (n = 307) at 33 centers. Mean age was 62.7 years (SD, 7.5); 66.1% of participants were female, 90% were White, 8.2% were Black, and 5.9% were Hispanic. The most common TNFi indications were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%); TNFi medications were adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). Concomitant therapies included methotrexate (48.0%) and oral glucocorticoids (10.5%). Through week 6, no cases of confirmed varicella infection were found; cumulative incidence of varicella infection or shingles was 0.0% (95% CI, 0.0% to 1.2%). At 6 weeks, compared with baseline, the mean increases in geometric mean fold rise as measured by gpELISA and ELISpot were 1.33 percentage points (CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (CI, 1.07 to 1.82 percentage points), respectively. LIMITATION Potentially limited generalizability to patients receiving other types of immunomodulators. CONCLUSION This trial informs safety concerns related to use of live virus vaccines in patients receiving biologics. PRIMARY FUNDING SOURCE The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.
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Affiliation(s)
- Jeffrey R Curtis
- Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, Alabama (J.R.C., S.K.)
| | - Stacey S Cofield
- Department of Biostatistics, The University of Alabama at Birmingham, Birmingham, Alabama (S.S.C., J.B.)
| | - S Louis Bridges
- Hospital for Special Surgery and Weill Cornell Medicine, New York, New York (S.L.B.)
| | - John Bassler
- Department of Biostatistics, The University of Alabama at Birmingham, Birmingham, Alabama (S.S.C., J.B.)
| | - Atul Deodhar
- Oregon Health & Science University, Portland, Oregon (A.D., S.A.S., K.L.W.)
| | - Theresa L Ford
- North Georgia Rheumatology Group, Lawrenceville, Georgia (T.L.F.)
| | | | - Allen Jankeel
- University of California, Irvine, Irvine, California (A.J., I.M., N.M.)
| | - Alan Kivitz
- Altoona Center for Clinical Research, Duncansville, Pennsylvania (A.K.)
| | - Shaila Kamal
- Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, Alabama (J.R.C., S.K.)
| | | | - Ilhem Messaoudi
- University of California, Irvine, Irvine, California (A.J., I.M., N.M.)
| | - Norma Mendoza
- University of California, Irvine, Irvine, California (A.J., I.M., N.M.)
| | - Kaleb Michaud
- University of Nebraska Medical Center, Omaha, Nebraska, and FORWARD-The National Databank for Rheumatic Diseases, Wichita, Kansas (K.M.)
| | - Ted R Mikuls
- University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska (T.R.M.)
| | - David Ridley
- St. Paul Rheumatology, P.A., Eagan, Minnesota (D.R.)
| | - William Shergy
- RANA - Rheumatology Associates of North Alabama, Huntsville, Alabama (W.S.)
| | - Sarah A R Siegel
- Oregon Health & Science University, Portland, Oregon (A.D., S.A.S., K.L.W.)
| | - Kevin L Winthrop
- Oregon Health & Science University, Portland, Oregon (A.D., S.A.S., K.L.W.)
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Qian J, Banks E, Macartney K, Heywood AE, Lassere MN, Liu B. Corticosteroid Use and Risk of Herpes Zoster in a Population-Based Cohort. Mayo Clin Proc 2021; 96:2843-2853. [PMID: 34736610 DOI: 10.1016/j.mayocp.2021.05.029] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 04/18/2021] [Accepted: 05/12/2021] [Indexed: 12/29/2022]
Abstract
OBJECTIVE To examine the relationship between corticosteroid use and herpes zoster risk. METHODS With data from a large cohort of adults (the 45 and Up Study) recruited between 2006 and 2009 and linked to health data sets, the effect of corticosteroid use on zoster risk was analyzed by Cox proportional hazards models, adjusting for age, sex, and other characteristics. RESULTS During 602,152 person-years (median, 7.36 years) of follow-up, there were 20,048 new systemic corticosteroid users and 6294 incident herpes zoster events among 94,677 participants (zoster incidence, 11.0 per 1000 person-years). Compared with nonusers, the risk of zoster was 59% higher in those using systemic corticosteroids (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.48 to 1.71) and greater with higher cumulative doses: aHR of 1.32 (95% CI, 1.17 to 1.48), 1.74 (95% CI, 1.55 to 1.95), and 1.80 (95% CI, 1.61 to 2.02) for use of less than 500 mg, 500 mg to less than 1000 mg, and 1000 mg or more prednisolone equivalents, respectively (P value for trend, <.001). Compared with nonusers, zoster risk increased significantly (aHR, 6.00; 95% CI, 4.85 to 7.42) in the month after a single prescription of systemic corticosteroids and returned to levels similar to those in nonusers by the third month after dispensing (aHR, 0.91; 95% CI, 0.49 to 1.69). CONCLUSION Practitioners should be alert to the increased risk of zoster among patients taking systemic corticosteroids. Given the significant morbidity from zoster, particularly in older adults, these findings support judicious prescribing of corticosteroids, including using as low a dose and as short a course as possible.
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Affiliation(s)
- Jiahui Qian
- School of Population Health, University of New South Wales, Sydney, NSW, Australia.
| | - Emily Banks
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia; The Sax Institute, Sydney, NSW, Australia
| | - Kristine Macartney
- National Centre for Immunisation Research and Surveillance, Westmead, NSW, Australia; Discipline of Child and Adolescent Health, University of Sydney, Sydney, NSW, Australia
| | | | - Marissa Nichole Lassere
- School of Population Health, University of New South Wales, Sydney, NSW, Australia; St George Hospital, Kogarah, NSW, Australia
| | - Bette Liu
- School of Population Health, University of New South Wales, Sydney, NSW, Australia
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Handley G, Hand J. Adverse Effects of Immunosuppression: Infections. Handb Exp Pharmacol 2021; 272:287-314. [PMID: 34671868 DOI: 10.1007/164_2021_550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Immunosuppressive therapies are currently indicated for a wide range of diseases. As new agents emerge and indications evolve the landscape grows increasingly complex. Therapies can target pathologic immune system over-activation in rheumatologic or autoimmune disease, or conditioning and graft versus host disease (GVHD) prophylactic regimens may eliminate or inhibit host immune function to improve graft survival and risk of complication in solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HSCT). With immunosuppressive therapy, infections occur. Complex disease states, host factors, and concomitant therapies contribute to a "net state" of immunosuppression that must be considered and may confound perceived increased infection risks in patients receiving treatment.
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Affiliation(s)
- Guy Handley
- Division of Infectious Disease and International Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
| | - Jonathan Hand
- Department of Infectious Diseases, Ochsner Health, The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA, USA.
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Sellam J, Morel J, Tournadre A, Bouhnik Y, Cornec D, Devauchelle-Pensec V, Dieudé P, Goupille P, Jullien D, Kluger N, Lazaro E, Le Goff B, de Lédinghen V, Lequerré T, Nocturne G, Seror R, Truchetet ME, Verhoeven F, Pham T, Richez C. PRACTICAL MANAGEMENT of patients on anti-TNF therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI). Joint Bone Spine 2021; 88:105174. [PMID: 33992225 DOI: 10.1016/j.jbspin.2021.105174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Jérémie Sellam
- Service de Rhumatologie, CHU Saint-Antoine, Paris, France
| | - Jacques Morel
- Service de Rhumatologie, CHU Montpellier, Montpellier, France
| | - Anne Tournadre
- Service de Rhumatologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Yoram Bouhnik
- Service de Gastro-entérologie, CHU Hôpital Beaujon, Clichy, France
| | - Divi Cornec
- Service de Rhumatologie, CHRU La Cavale Blanche, Brest, France
| | | | - Philippe Dieudé
- Service de Rhumatologie, CHU Bichat-Claude Bernard, Paris, France
| | | | | | - Nicolas Kluger
- Dpt Dermatology, Helsinki, Finland; Service de Dermatologie, CHU Bichat-Claude Bernard, Paris, France
| | - Estibaliz Lazaro
- Service de Médecine interne, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France
| | | | - Victor de Lédinghen
- Unité d'Hépatologie et transplantation hépatique, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France
| | | | | | - Raphaèle Seror
- Service de Rhumatologie, Bicêtre, Le Kremlin-Bicêtre, France
| | | | | | - Thao Pham
- Service de Rhumatologie, CHU Sainte-Marguerite, Marseille, France
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Dörner T, Schett G. [80 milestones in rheumatology from 80 years-IV. 2000-2020]. Z Rheumatol 2021; 80:528-538. [PMID: 34255165 DOI: 10.1007/s00393-021-01038-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/04/2021] [Indexed: 10/20/2022]
Affiliation(s)
- T Dörner
- Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Charité-Universitätsmedizin Berlin, Berlin, Deutschland.,Deutsches Rheuma Forschungszentrum Berlin, Berlin, Deutschland
| | - G Schett
- Medizinische Klinik 3, Friedrich-Alexander-Universität Erlangen-Nürnberg und Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Deutschland. .,Deutsches Zentrum für Immuntherapie, Friedrich-Alexander-Universität Erlangen-Nürnberg und Universitätsklinikum Erlangen, Erlangen, Deutschland.
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Winthrop KL, Loftus EV, Baumgart DC, Reinisch W, Nduaka CI, Lawendy N, Chan G, Mundayat R, Friedman GS, Salese L, Thorpe AJ, Su C. Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Infection Rates from the Ulcerative Colitis Clinical Programme. J Crohns Colitis 2021; 15:914-929. [PMID: 33245746 PMCID: PMC8218715 DOI: 10.1093/ecco-jcc/jjaa233] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIMS Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes. METHODS Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance, or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious], and opportunistic infections [OIs] are reported [censored at time of event]. RESULTS In the Induction Cohort [N = 1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10 mg twice daily [BID] developed SIs. Maintenance Cohort [N = 592] SI IRs (95% confidence interval [CI]) were 1.94 [0.23-7.00] for placebo and 1.35 [0.16-4.87] and 0.64 [0.02-3.54] for tofacitinib 5 and 10 mg BID, respectively; HZ IRs were 0.97 [0.02-5.42], 2.05 [0.42-6.00], and 6.64 [3.19-12.22], respectively. In the Overall Cohort [N = 1157; 82.9% predominantly received tofacitinib 10 mg BID], SI, HZ, and non-HZ OI IRs were 1.70 [1.24-2.27], 3.48 [2.79-4.30], and 0.15 [0.04-0.38], respectively. No SIs resulted in death. CONCLUSIONS During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 mg BID versus 5 mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.
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Affiliation(s)
- Kevin L Winthrop
- Division of Infectious Diseases, Oregon Health & Science University, Portland, OR, USA
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Daniel C Baumgart
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Walter Reinisch
- Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Chudy I Nduaka
- Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA
| | - Nervin Lawendy
- Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA
| | - Gary Chan
- Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA
| | - Rajiv Mundayat
- Inflammation and Immunology, Pfizer Inc, New York, NY, USA
| | - Gary S Friedman
- Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA
| | - Leonardo Salese
- Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA
| | - Andrew J Thorpe
- Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA
| | - Chinyu Su
- Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA
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Dernoncourt A, Schmidt J, Duhaut P, Liabeuf S, Gras-Champel V, Masmoudi K, Bennis Y, Batteux B. COVID-19 in DMARD-treated patients with inflammatory rheumatic diseases: Insights from an analysis of the World Health Organization pharmacovigilance database. Fundam Clin Pharmacol 2021; 36:199-209. [PMID: 33973280 PMCID: PMC8239613 DOI: 10.1111/fcp.12695] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 04/09/2021] [Accepted: 05/06/2021] [Indexed: 12/31/2022]
Abstract
Background To determine whether the use of disease‐modifying antirheumatic drugs (DMARDs) is linked to the risk of COVID‐19 among patients with inflammatory rheumatic diseases (IRDs). Methods We performed a disproportionality analysis of the World Health Organization pharmacovigilance database between January 1, 2020, and June 10, 2020. The frequency of COVID‐19 reports for all DMARD classes identified was compared with that for all other reports for all other drugs and quoted as the reporting odds ratio (ROR) (95% confidence interval [CI]). Results Among 980,446 individual case‐safety reports voluntarily recorded in the database, 398 identified COVID‐19 in DMARD‐treated patients with IRDs. There were 177 (44.5%) patients with rheumatoid arthritis (RA), 120 (30.1%) with ankylosing spondylitis (AS), 93 (23.4%) with psoriatic arthritis (PsA), and 8 (2.0%) with juvenile idiopathic arthritis. Most of the cases of COVID‐19 occurred in patients taking anti‐TNF agents (84.2%), resulting in a significant disproportionality signal (ROR [95% CI]: 8.31 [7.48–9.23]) – particularly in patients with RA, AS or PsA. A significant inverse disproportionality was found for the anti‐IL‐6 agent tocilizumab (ROR [95% CI]: 0.12 [0.02–0.88]) and JAK inhibitors (ROR [95% CI]: 0.33 [0.19–0.58]) in patients with RA – suggesting that these two drug classes are safer in the context of RA. Conclusion Our results are in line with the literature on a potentially better safety profile for anti‐IL‐6 agents and JAK inhibitors. The WHO pharmacovigilance data suggest that COVID‐19 is significantly more frequent in patients with IRDs treated with TNF inhibitors.
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Affiliation(s)
- Amandine Dernoncourt
- Department of Internal Medicine, Amiens-Picardie University Medical Center, Amiens, France.,RECIF, Amiens-Picardie University Medical Center, Amiens, France
| | - Jean Schmidt
- Department of Internal Medicine, Amiens-Picardie University Medical Center, Amiens, France.,RECIF, Amiens-Picardie University Medical Center, Amiens, France
| | - Pierre Duhaut
- Department of Internal Medicine, Amiens-Picardie University Medical Center, Amiens, France.,RECIF, Amiens-Picardie University Medical Center, Amiens, France
| | - Sophie Liabeuf
- Department of Clinical Pharmacology, Amiens University Medical Center, Amiens, France.,MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France
| | - Valérie Gras-Champel
- Department of Clinical Pharmacology, Amiens University Medical Center, Amiens, France.,MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France
| | - Kamel Masmoudi
- Department of Clinical Pharmacology, Amiens University Medical Center, Amiens, France
| | - Youssef Bennis
- Department of Clinical Pharmacology, Amiens University Medical Center, Amiens, France.,MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France
| | - Benjamin Batteux
- RECIF, Amiens-Picardie University Medical Center, Amiens, France.,Department of Clinical Pharmacology, Amiens University Medical Center, Amiens, France.,MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France.,Department of Rheumatology, Saint-Quentin Medical Center, Saint-Quentin, France
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Kour G, Haq SA, Bajaj BK, Gupta PN, Ahmed Z. Phytochemical add-on therapy to DMARDs therapy in rheumatoid arthritis: In vitro and in vivo bases, clinical evidence and future trends. Pharmacol Res 2021; 169:105618. [PMID: 33878447 DOI: 10.1016/j.phrs.2021.105618] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 03/25/2021] [Accepted: 04/13/2021] [Indexed: 02/07/2023]
Abstract
The use of biologically active compounds derived from plants i.e. phytochemicals, have been known for ages for their pharmacological activities in the treatment of autoimmune disorders like rheumatoid arthritis (RA). Besides enormous scientific evidence, the therapeutic potential of phytochemicals is often undervalued. The treatment in RA involves the use of synthetic and biological disease modifying anti-rheumatic drugs (DMARDs). However, the long-term treatment in RA is associated with the risk of gastrointestinal, liver, pulmonary and renal toxicities and serious infections including latent tuberculosis, pneumococcus influenza, herpes zoster and hepatitis. These adverse effects sometimes lead to discontinuation of the therapy. A relatively new vision based on the combination of DMARDs with phytochemicals exhibiting anti-inflammatory, anti-arthritic, anti-oxidant, hepatoprotective and nephroprotective properties for the treatment of RA has achieved substantial importance in the last decade. From this perspective, the present review focuses on the combination of DMARDs (primarily MTX) with phytochemicals that have shown synergistic therapeutic effects while decreasing the toxic repercussions of current RA therapy. The review covers recent evidences of such combination studies that have shown promising results both in experimental arthritic models and clinical arthritis. Few of the combinations including resveratrol, sinomenine, coenzyme Q10 exhibited considerable interest because of their efficacy as an adjuvant to the MTX/standard DMARDs therapy in clinical trials. Besides giving an overview of such combination studies the review also critically discusses the limitations with the use of phytochemicals (e.g. solubility, permeability and bioavailability) compromising their clinical application. Additionally, it stresses upon the need of novel delivery systems and pharmaceutical technologies to increase the therapeutic efficacy of the combination therapy. Overall, the review unveils the potential of phytochemicals in combination with DMARDs with increased tolerability and superior efficacy in further refining the future of the RA therapy.
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Affiliation(s)
- Gurleen Kour
- Inflammation Pharmacology Division, CSIR, Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, J&K, India; School of Biotechnology, University of Jammu, Baba Saheb Ambedkar Road, Jammu Tawi, 180006 J&K, India
| | - Syed Assim Haq
- Formulation & Drug Delivery Division, CSIR, Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, J&K, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Bijender Kumar Bajaj
- School of Biotechnology, University of Jammu, Baba Saheb Ambedkar Road, Jammu Tawi, 180006 J&K, India
| | - Prem N Gupta
- Formulation & Drug Delivery Division, CSIR, Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, J&K, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
| | - Zabeer Ahmed
- Inflammation Pharmacology Division, CSIR, Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, J&K, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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Bechman K, Halai K, Yates M, Norton S, Cope AP, Hyrich KL, Galloway JB. Nonserious Infections in Patients With Rheumatoid Arthritis: Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Arthritis Rheumatol 2021; 73:1800-1809. [PMID: 33844458 DOI: 10.1002/art.41754] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 03/25/2021] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To describe the frequency and predictors of nonserious infections (NSI) and compare incidence across biologic agents within the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA). METHODS The BSRBR-RA is a prospective observational cohort study. An NSI was defined as an infection that did not require hospitalization or intravenous therapy. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered "at risk" from the date of initiation of biologic treatment for up to 3 years. Drug exposure was defined by agent: tumor necrosis factor inhibitor (TNFi), interleukin-6 (IL-6) inhibitor, B cell depletion (rituximab), or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) alone. A multiple-failure Cox model was used with multivariable adjustment. Missing data were addressed using multiple imputation. RESULTS There were 17,304 NSI in 8,145 patients, with an event rate of 27.0 per person per year (95% confidence interval [95% CI] 26.6-27.4). Increasing age, female sex, comorbidity burden, glucocorticoid therapy, higher Disease Activity Score in 28 joints, and higher Health Assessment Questionnaire disability index were associated with an increased risk of NSI. There was a significant reduction in NSI risk with csDMARDs compared to biologic treatments. Compared to TNFi, IL-6 inhibition and rituximab were associated with a higher NSI risk (adjusted hazard ratio 1.45 [95% CI 1.29-1.63] and adjusted hazard ratio 1.28 [95% CI 1.14-1.45], respectively), while the csDMARD cohort had a lower risk (adjusted hazard ratio 0.64 [95% CI 0.59-0.70]). Within the TNFi class, adalimumab was associated with a higher NSI risk than etanercept (adjusted hazard ratio 1.11 [95% CI 1.05-1.17]). CONCLUSION NSI occur frequently in RA, and predictors mirror those reported with serious infections. All biologics are associated with a greater risk of NSI, with differences observed between agents. While unmeasured confounding must be considered, the magnitude of effect is large, and a relationship between NSI and targeted immunomodulatory therapy likely exists.
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Affiliation(s)
| | | | | | | | | | | | - Kimme L Hyrich
- Manchester Academic Health Sciences Centre, University of Manchester, NIHR Manchester Biomedical Research Centre, and Manchester University NHS Foundation Trust, Manchester, UK
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Yates M, Mootoo A, Adas M, Bechman K, Rampes S, Patel V, Qureshi S, Cope AP, Norton S, Galloway JB. Venous Thromboembolism Risk With JAK Inhibitors: A Meta-Analysis. Arthritis Rheumatol 2021; 73:779-788. [PMID: 33174384 DOI: 10.1002/art.41580] [Citation(s) in RCA: 99] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 10/14/2020] [Accepted: 11/23/2020] [Indexed: 01/20/2023]
Abstract
OBJECTIVE JAK inhibitor therapies are effective treatment options for immune-mediated inflammatory diseases (IMIDs), but their use has been limited by venous thromboembolism (VTE) risk warnings from licensing authorities. We undertook this study to evaluate the VTE risk of JAK inhibitors in patients with IMIDs. METHODS Systematic searches of Medline and Embase databases from inception to September 30, 2020 were conducted. Phase II and phase III double-blind, randomized controlled trials (RCTs) of JAK inhibitors at licensed doses were included in our analyses. RCTs with no placebo arm, long-term extension studies, post hoc analyses, and pooled analyses were excluded. Three researchers independently extracted data on exposure to JAK inhibitors or placebo and VTE events (e.g., pulmonary embolism [PE] and deep vein thrombosis [DVT]) and assessed study quality. RESULTS A total of 42 studies were included, from an initial search that yielded 619. There were 6,542 JAK inhibitor patient exposure years (PEYs) compared to 1,578 placebo PEYs. There were 15 VTE events in the JAK inhibitor group and 4 in the placebo group. The pooled incidence rate ratios (IRRs) of VTE, PE, and DVT in patients receiving JAK inhibitors were 0.68 (95% confidence interval [95% CI] 0.36-1.29), 0.44 (95% CI 0.28-0.70), and 0.59 (95% CI 0.31-1.15), respectively. CONCLUSION This meta-analysis of RCT data defines the VTE risk with JAK inhibitors as a class in IMID patients. The pooled IRRs do not provide evidence that support the current warnings of VTE risk for JAK inhibitors. These findings will aid continued development of clinical guidelines for the use of JAK inhibitors in IMIDs.
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46
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Kobak S. Tofacitinib-induced Ramsay- Hunt Syndrome in a Patient with Rheumatoid Arthritis. Curr Drug Saf 2021; 16:107-109. [PMID: 32819263 DOI: 10.2174/1574886315999200819153827] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 07/25/2020] [Accepted: 07/29/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint and systemic involvement. Tofacitinib is a JAK- inhibitor that is an effective agent in the treatment of active RA. Varicella zoster virus(VZV) reactivation is among the most important adverse effects of tofacitinib. Ramsay-Hunt syndrome(RHS) is a rare clinical condition that develops as a result of VZV reactivation and progresses with hearing loss, dizziness, and facial nerve paralysis. OBJECTIVE To present a case of Ramsay-Hunt syndrome due to varicella zoster reactivation in a RA patient using tofacitinib. CASE REPORT A 63-year-old female RA patient under tofacitinib treatment was admitted to the rheumatology outpatient clinic due to widespread skin rashes on her face and ear, and hearing loss. On inspection widespread erythematous, vesicular rashes on the left side of the face, lips, around the eye and in the ear, and mild facial paralysis on the left side were detected. On laboratory investigations, acute phase reactants were increased. Serological study for specific antibodies against varicella zoster virus showed higher titers. Dermatology and ear nose throat specialist consultations were performed, and varicella zoster lesions on the left inner ear, face, and mild facial paresis were considered. According to clinical and laboratory findings, the patient was diagnosed with RHS triggered by tofacitinib. Tofacitinib and methotrexate were discontinued, and intravenous acyclovir was started. On the control examination, the patient's skin lesions and facial nerve paralysis regressed. CONCLUSION Herein, we reported the fırst case of tofacitinib-induced RHS in a patient with RA. This may be another side effect of biologic treatment. New studies are needed on this subject.
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Affiliation(s)
- Senol Kobak
- Department of Rheumatology, Istinye University Faculty of Medicine, LIV Hospital, Istanbul, Turkey
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47
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Thiele F, Klein A, Windschall D, Hospach A, Foeldvari I, Minden K, Weller-Heinemann F, Horneff G. Comparative risk of infections among real-world users of biologics for juvenile idiopathic arthritis: data from the German BIKER registry. Rheumatol Int 2021; 41:751-762. [PMID: 33590331 PMCID: PMC7952348 DOI: 10.1007/s00296-020-04774-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 12/17/2020] [Indexed: 01/30/2023]
Abstract
To examine whether treatment with interleukin (IL)-1-, IL-6-, tumour necrosis factor α (TNFα)-inhibitors or Abatacept is associated with an increased risk of common infections, infections requiring hospitalization (SAE) or opportunistic infections among real-world juvenile idiopathic arthritis (JIA) patients. Furthermore, the influence of other patient-related covariates on the occurrence of infections was investigated. Patients diagnosed with JIA and treated with biologics were selected from the German BIKER registry. Incidence rates (IR) of infections per 100 person years were calculated and compared between the different cohorts. Using multivariate logistic regression, odds ratios with 95% confidence intervals (CI) were determined for the influence of patient-related covariates (age, diagnosis, laboratory data, concomitant medication, JIA activity, comorbidities, and premedication) on the occurrence of infections. 3258 patients entered the analysis. A total of 3654 treatment episodes were distributed among TNFα- (Etanercept, Adalimumab, Golimumab, Infliximab, n = 3044), IL-1- (Anakinra, Canakinumab, n = 105), IL-6- (Tocilizumab, n = 400) and T-cell activation inhibitors (Abatacept, n = 105). 813 (22.2%) patients had at least one infection, 103 (2.8%) patients suffered from an SAE infection. Both common and SAE infections were significantly more frequent in IL-1 (IR 17.3, 95% CI 12.5/24 and IR 4.3, 95% CI 2.3/8.3) and IL-6 cohort (IR 16.7, 95% CI 13.9/20 and IR 2.8, 95% CI 1.8/4.4) compared to TNFα-inhibitor cohort (IR 8.7, 95% CI 8.1/9.4 and IR 1, 95% CI 0.8/1.3). When comparing the influencing factors for various infectious diseases, the use of corticosteroids, younger age, cardiac comorbidities and higher JIA-activity are the most striking risk factors. Relative to TNFα inhibitors and Abatacept, IL-1 and IL-6 inhibitors were associated with an increased risk of common and SAE infections. The influencing covariates identified may be helpful for the choice of a suitable biologic to treat JIA.
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Affiliation(s)
- Franz Thiele
- Centre for Paediatric Rheumatology, Department of General Paediatrics, Asklepios Clinic Sankt Augustin, 53757, Sankt Augustin, Germany.
| | - Ariane Klein
- Centre for Paediatric Rheumatology, Department of General Paediatrics, Asklepios Clinic Sankt Augustin, 53757, Sankt Augustin, Germany.,Medical Faculty, University of Cologne, Cologne, Germany
| | - Daniel Windschall
- Clinic for Paediatric and Adolescent Rheumatology, St. Josef-Stift Sendenhorst, Northwest German Center for Rheumatology, Sendenhorst, Germany
| | - Anton Hospach
- Centre for Paediatric Rheumatology, Klinikum Stuttgart, Germany
| | - Ivan Foeldvari
- Hamburger Zentrum Für Kinder- Und Jugendrheumatologie, Hamburg, Germany
| | | | | | - Gerd Horneff
- Centre for Paediatric Rheumatology, Department of General Paediatrics, Asklepios Clinic Sankt Augustin, 53757, Sankt Augustin, Germany.,Medical Faculty, University of Cologne, Cologne, Germany
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48
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Ye C, Zhong J, Cai S, Dong L, Li C, Hou X, Chen X, Zhang A, Chen W, He D, Zhou T, Shang G, Chu A, Li H, Liu Q, Wu B, Yu X, Peng T, Wen C, Huang GH, Huang H, Huang Q, Su L, Chen W, Yang H, Dong L. COVID-19 infection in patients with connective tissue disease: A multicity study in Hubei province, China. MedComm (Beijing) 2021; 2:82-90. [PMID: 33821253 PMCID: PMC8013216 DOI: 10.1002/mco2.56] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 01/04/2021] [Accepted: 01/05/2021] [Indexed: 12/27/2022] Open
Abstract
Novel Coronavirus disease 2019 (COVID-19) has spread rapidly around the world. Individuals with immune dysregulation and/or on immunosuppressive therapy, such as rheumatic patients, are considered at greater risk for infections. However, the risks of patients with each subcategory of rheumatic diseases have not been reported. Here, we identified 100 rheumatic patients from 18,786 COVID-19 patients hospitalized in 23 centers affiliated to Hubei COVID-19 Rheumatology Alliance between January 1 and April 1, 2020. Demographic information, medical history, length of hospital stay, classification of disease severity, symptoms and signs, laboratory tests, disease outcome, computed tomography, and treatments information were collected. Compared to gout and ankylosing spondylitis (AS) patients, patients with connective tissue disease (CTD) tend to be more severe after COVID-19 infection (p = 0.081). CTD patients also had lower lymphocyte counts, hemoglobin, and platelet counts (p values were 0.033, < 0.001, and 0.071, respectively). Hydroxychloroquine therapy and low- to medium-dose glucocorticoids before COVID-19 diagnosis reduced the progression of COVID-19 to severe/critical conditions (p = 0.001 for hydroxychloroquine; p = 0.006 for glucocorticoids). Our data suggests that COVID-19 in CTD patients may be more severe compared to patients with AS or gout.
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Affiliation(s)
- Cong Ye
- Department of Rheumatology and Immunology Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology Wuhan Hubei China
| | - Jixin Zhong
- Department of Rheumatology and Immunology Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology Wuhan Hubei China
| | - Shaozhe Cai
- Department of Rheumatology and Immunology Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology Wuhan Hubei China
| | - Li Dong
- Jingzhou City Central Hospital of Hubei Province Jingzhou Hubei China
| | - Chuanjing Li
- Department of Rheumatology Xiaogan Hospital Affiliated to Wuhan University of Science and Technology Xiaogan Hubei China
| | - Xiaoqiang Hou
- The First College of Clinical Medical Sciences China Three Gorges University Yichang Hubei China
| | - Xiaoqi Chen
- Department of Rheumatology Zhongnan Hospital of Wuhan University Wuhan Hubei China
| | - Anbing Zhang
- Department of Rheumatology and Immunology Xiangyang Central Hospital Xiangyang Hubei China
| | - Wenli Chen
- Department of Rheumatology and Immunology Wuhan Central Hospital Wuhan Hubei China
| | - Dongchu He
- Department of Integrated Treatment General Hospital of Central Theater Command Wuhan Hubei China
| | - Tao Zhou
- Department of Rheumatology and Immunology Wuhan Puren Hospital Affiliated to Wuhan University of Science and Technology Wuhan Hubei China
| | - Guilian Shang
- Department of Rheumatology and Immunology Tianyou Hospital Affiliated to Wuhan University of Science and Technology Wuhan Hubei China
| | - Aichun Chu
- Department of Prevention and Health Care Renmin Hospital of Wuhan University Wuhan Hubei China
| | - Huiling Li
- Department of Rheumatology and Immunology The Traditional Chinese Medical Hospital of Hubei Province Wuhan Hubei China
| | - Qihuan Liu
- Department of Rheumatology and Immunology Affliated Dongfeng Hospital Hubei University of Medicine Shiyan Hubei China
| | - Bin Wu
- Department of Rheumatology and Immunology The First People's Hospital of Jingzhou Jingzhou Hubei China
| | - Xiangdong Yu
- Department of Rheumatology and Immunology Huangshi Central Hospital of Edong Healthcare Group Huangshi Hubei China
| | - Tao Peng
- Department of Rheumatology and Immunology Hankou Hospital of Wuhan Wuhan Hubei China
| | - Cheng Wen
- Department of Endocrinology Xiaogan First People's Hospital Xiaogan Hubei China
| | - Gang Hong Huang
- Department of Rheumatology and Immunology China Resources and Wisco General Hospital Wuhan Hubei China
| | - Hao Huang
- Department of Rheumatology and Immunology The First People's Hospital of Tianmen Tianmen Hubei China
| | - Qin Huang
- Department of Nephrology and Rheumatology Enshi Tujia and Miao Autonomous Prefecture Central Hospital Enshi Hubei China
| | - Linchong Su
- Department of Rheumatology and Immunology Minda Hospital of Hubei Minzu University Enshi Hubei China
| | - Wenping Chen
- Department of Rheumatology and Immunology Huanggang Central HospitaI Huanggang Hubei China
| | - Huiqin Yang
- Department of Rheumatology and Immunology Wuhan No.1 Hospital Wuhan Hubei China
| | - Lingli Dong
- Department of Rheumatology and Immunology Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology Wuhan Hubei China
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Antonelli E, Bassotti G, Tramontana M, Hansel K, Stingeni L, Ardizzone S, Genovese G, Marzano AV, Maconi G. Dermatological Manifestations in Inflammatory Bowel Diseases. J Clin Med 2021; 10:jcm10020364. [PMID: 33477990 PMCID: PMC7835974 DOI: 10.3390/jcm10020364] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/04/2021] [Accepted: 01/06/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) may be associated with extra-intestinal manifestations. Among these, mucocutaneous manifestations are relatively frequent, often difficult to diagnose and treat, and may complicate the course of the underlying disease. In the present review, a summary of the most relevant literature on the dermatologic manifestations occurring in patients with inflammatory bowel diseases has been reviewed. The following dermatological manifestations associated with IBDs have been identified: (i) specific manifestations with the same histological features of the underlying IBD (occurring only in Crohn's disease); (ii) cutaneous disorders associated with IBDs (such as aphthous stomatitis, erythema nodosum, psoriasis, epidermolysis bullosa acquisita); (iii) reactive mucocutaneous manifestations of IBDs (such as pyoderma gangrenosum, Sweet's syndrome, bowel-associated dermatosis-arthritis syndrome, aseptic abscess ulcers, pyodermatitis-pyostomatitis vegetans, etc.); (iv) mucocutaneous conditions secondary to treatment (including injection site reactions, infusion reactions, paradoxical reactions, eczematous and psoriasis-like reactions, cutaneous infections, and cutaneous malignancies); (v) manifestations due to nutritional malabsorption (such as stomatitis, glossitis, angular cheilitis, pellagra, scurvy, purpura, acrodermatitis enteropathica, phrynoderma, seborrheic-type dermatitis, hair and nail abnormalities). An accurate dermatological examination is essential in all IBD patients, especially in candidates to biologic therapies, in whom drug-induced cutaneous reactions may assume marked clinical relevance.
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Affiliation(s)
| | - Gabrio Bassotti
- Gastroenterology Section, Perugia General Hospital, 06156 Perugia, Italy;
- Gastroenterology & Hepatology Section, Department of Medicine, University of Perugia, 06156 Perugia, Italy
- Correspondence:
| | - Marta Tramontana
- Dermatology Section, Department of Medicine, University of Perugia, 06156 Perugia, Italy; (M.T.); (K.H.); (L.S.)
| | - Katharina Hansel
- Dermatology Section, Department of Medicine, University of Perugia, 06156 Perugia, Italy; (M.T.); (K.H.); (L.S.)
| | - Luca Stingeni
- Dermatology Section, Department of Medicine, University of Perugia, 06156 Perugia, Italy; (M.T.); (K.H.); (L.S.)
| | - Sandro Ardizzone
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, “L.Sacco” Hospital, 20157 Milano, Italy; (S.A.); (G.M.)
| | - Giovanni Genovese
- Dermatology Unit, Fondazione IRCSS Cà Granda, Ospedale Maggiore Policlinico, 20122 Milano, Italy; (G.G.); (A.V.M.)
- Department of Pathophysiology and Transplantation, University of Milano, 20122 Milano, Italy
| | - Angelo Valerio Marzano
- Dermatology Unit, Fondazione IRCSS Cà Granda, Ospedale Maggiore Policlinico, 20122 Milano, Italy; (G.G.); (A.V.M.)
- Department of Pathophysiology and Transplantation, University of Milano, 20122 Milano, Italy
| | - Giovanni Maconi
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, “L.Sacco” Hospital, 20157 Milano, Italy; (S.A.); (G.M.)
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Caldera F, Ley D, Hayney MS, Farraye FA. Optimizing Immunization Strategies in Patients with IBD. Inflamm Bowel Dis 2021; 27:123-133. [PMID: 32232388 DOI: 10.1093/ibd/izaa055] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Indexed: 02/07/2023]
Abstract
Recent advances in the treatment of inflammatory bowel disease (IBD) include the use of immune modifiers and monoclonal antibodies, such as tumor necrosis factor (TNF) alpha inhibitors, anti-integrin agents, janus kinase inhibitors, and interleukin-12/23 inhibitors. These agents achieve higher rates of clinical remission and mucosal healing than conventional therapy. However, these therapies increase the risk of infections, including some vaccine-preventable diseases. Infections are one of the most common adverse event of immunosuppressive therapy. Thus, providers should optimize immunization strategies to reduce the risk of vaccine-preventable infections in patients with IBD. There are several newly licensed vaccines recommended for adults by the US Advisory Committee on Immunization Practices. This review will focus on how gastroenterology providers can implement the adult immunization schedule approved by ACIP for patients with IBD.
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Affiliation(s)
- Freddy Caldera
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin-Madison, School of Medicine & Public Health, Madison, WI
| | - Dana Ley
- Department of Medicine, Division of Internal Medicine, University of Wisconsin-Madison, School of Medicine & Public Health, Madison, WI
| | - Mary S Hayney
- School of Pharmacy, University of Wisconsin-Madison, School of Medicine & Public Health, Madison, WI
| | - Francis A Farraye
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
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