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Hradsky O, Copova I, Durilova M, Kazeka D, Lerchova T, Mitrova K, Schwarz J, Vetrovcova R, El-Lababidi N, Karaskova E, Veghova-Velganova M, Sulakova A, Gonsorčíková L, Veverkova M, Zeniskova I, Zimen M, Bortlik M, Bronsky J. Sustainability of biologic treatment in paediatric patients with Crohn's disease: population-based registry analysis. Pediatr Res 2024; 96:1283-1291. [PMID: 38012309 DOI: 10.1038/s41390-023-02913-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 08/29/2023] [Accepted: 10/20/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND We aimed to evaluate the predictors of sustainability of biologic drugs for paediatric patients with Crohn's disease (CD). METHODS The Czech National Prospective Registry of Biologic and Targeted Therapy of Inflammatory Bowel Disease (CREdIT) was used to identify the biologic treatment courses in paediatric patients with CD. Mixed-effects Cox models and propensity score analyses were employed to evaluate predictors of treatment sustainability. RESULTS Among the 558 observations of 473 patients, 264 were treated with adalimumab (47%), 240 with infliximab (43%), 41 with ustekinumab (7%), and 13 with vedolizumab (2%). Multivariable analysis revealed higher discontinuation risk with infliximab compared to adalimumab (HR = 0.600, 95%CI 0.389-0.926), both overall and in first-line treatment (HR = 0.302, 95%CI 0.103-0.890). Infliximab versus adalimumab was associated with shorter time to escalation (HR = 0.094, 95%CI 0.043-0.203). Propensity-score analysis demonstrated lower sustainability of infliximab (HR = 0.563, 95%CI 1.159-2.725). The time since diagnosis to treatment initiation (HR = 0.852, 95%CI 0.781-0.926) was the most important predictor. Baseline immunosuppressive therapy prolonged sustainability with infliximab (HR = 2.899, 95%CI 1.311-6.410). CONCLUSIONS Given the results suggesting shorter sustainability, the need for earlier intensification and thus higher drug exposure, and the greater need for immunosuppression with infliximab than with adalimumab, the choice of these drugs cannot be considered completely equitable. IMPACT Our study identified predictors of sustainability of biologic treatment in paediatric patients with Crohn's disease, including adalimumab (versus infliximab), early initiation of biologic treatment, and normalised baseline haemoglobin levels. Infliximab treatment was associated with earlier intensification, higher drug exposure, and a greater need for immunosuppression. Parents and patients should be fully informed of the disadvantages of intravenous infliximab versus adalimumab during the decision-making process. This study emphasises the importance of not delaying the initiation of biologic therapy in paediatric patients with Crohn's disease.
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Affiliation(s)
- Ondrej Hradsky
- Department of Paediatrics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
| | - Ivana Copova
- Department of Paediatrics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
| | - Marianna Durilova
- Department of Paediatrics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
| | - Denis Kazeka
- Department of Paediatrics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
| | - Tereza Lerchova
- Department of Paediatrics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
| | - Katarina Mitrova
- Department of Paediatrics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
| | - Jan Schwarz
- Department of Paediatrics, Faculty of Medicine in Pilsen, Faculty Hospital, Charles University in Prague, Pilsen, Czech Republic
| | - Romana Vetrovcova
- Department of Paediatrics, Faculty of Medicine in Pilsen, Faculty Hospital, Charles University in Prague, Pilsen, Czech Republic
| | - Nabil El-Lababidi
- Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Eva Karaskova
- Department of Paediatrics, Faculty of Medicine and Dentistry, University Hospital Olomouc, Olomouc, Czech Republic
| | - Maria Veghova-Velganova
- Department of Paediatrics, Faculty of Medicine and Dentistry, University Hospital Olomouc, Olomouc, Czech Republic
| | - Astrid Sulakova
- Department of Paediatrics, University Hospital Ostrava and Medical Faculty University of Ostrava, Ostrava, Czech Republic
| | - Lucie Gonsorčíková
- Department of Paediatrics, First Faculty of Medicine, Thomayer University Hospital and Charles University, Prague, Czech Republic
| | - Marketa Veverkova
- Department of Paediatrics, Faculty of Medicine, Masaryk University and University Hospital Brno, Brno, Czech Republic
| | - Ivana Zeniskova
- Department of Paediatrics, Hospital Ceske Budejovice, Ceske Budejovice, Czech Republic
| | - Martin Zimen
- Department of Paediatrics, Hospital Jihlava, Jihlava, Czech Republic
| | - Martin Bortlik
- Department of Gastroenterology, Hospital Ceske Budejovice, Ceske Budejovice, Czech Republic
- Department of Internal Medicine and Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jiri Bronsky
- Department of Paediatrics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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Kamal ME, Werida RH, Radwan MA, Askar SR, Omran GA, El-Mohamdy MA, Hagag RS. Efficacy and safety of infliximab and adalimumab in inflammatory bowel disease patients. Inflammopharmacology 2024; 32:3259-3269. [PMID: 38985232 PMCID: PMC11416362 DOI: 10.1007/s10787-024-01508-w] [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: 04/18/2024] [Accepted: 06/06/2024] [Indexed: 07/11/2024]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn's Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD. AIM This study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD. METHOD This study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn's Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period. RESULTS In the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002). CONCLUSION Both IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients. CLINICAL TRIAL REGISTRATION This study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022).
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Affiliation(s)
- Mahmoud E Kamal
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt.
| | - Rehab H Werida
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Mahasen A Radwan
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
| | - Safaa R Askar
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Gamal A Omran
- Biochemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Marwa A El-Mohamdy
- Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Radwa S Hagag
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
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de Souza LR, Magro DO, Teixeira FV, Parra RS, Miranda EF, Féres O, Saad-Hossne R, Soares Prates Herrerias G, Nisihara RM, Coy CSR, Sassaki LY, Kotze PG. Adalimumab Serum Concentrations, Clinical and Endoscopic Disease Activity in Crohn's Disease: A Cross-Sectional Multicentric Latin American Study. Pharmaceutics 2023; 15:586. [PMID: 36839908 PMCID: PMC9967155 DOI: 10.3390/pharmaceutics15020586] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/30/2023] [Accepted: 02/03/2023] [Indexed: 02/12/2023] Open
Abstract
Despite some variability in ideal serum Adalimumab (ADA) concentrations, there is increasing evidence that higher concentrations of anti-TNF-α agents can be associated with sustained efficacy, and low or undetectable levels may lead to loss of response. This study aims to correlate serum ADA concentrations with clinical and endoscopic activity in patients with Crohn's disease (CD). A cross-sectional and multicentric study was performed with patients with CD, who used ADA for at least 24 weeks. Patients were allocated into groups according to the presence of clinical or endoscopic disease activity. Serum ADA concentrations were measured and compared between groups. Overall, 89 patients were included. A total of 27 patients had clinically active CD and 62 were in clinical remission. Forty patients had endoscopic disease activity and 49 were in endoscopic remission. The mean serum ADA concentration was 10.2 μg/mL in patients with clinically active CD and 14.3 μg/mL in patients in clinical remission (p = 0.395). The mean serum ADA concentration in patients with endoscopic activity was 11.3 μg/mL as compared to 14.5 μg/mL in those with endoscopic remission (p = 0.566). There was no difference between serum ADA concentrations regarding clinical or endoscopic activity in CD, as compared to patients in remission.
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Affiliation(s)
| | - Daniela Oliveira Magro
- Colorectal Surgery Unit, Universidade Estadual de Campinas, UNICAMP, Campinas 13083-970, Brazil
| | | | - Rogério Serafim Parra
- Colorectal Surgery Unit, Universidade de São Paulo, USP, Ribeirão Preto 05508-090, Brazil
| | - Eron Fábio Miranda
- Colorectal Surgery Unit, Pontificia Universidade Católica do Paraná, PUCPR, Curitiba 80910-215, Brazil
| | - Omar Féres
- Colorectal Surgery Unit, Universidade de São Paulo, USP, Ribeirão Preto 05508-090, Brazil
| | - Rogério Saad-Hossne
- IBD Outpatient Clinics, São Paulo State University, UNESP, Botucatu 01049-010, Brazil
| | | | | | | | - Ligia Yukie Sassaki
- IBD Outpatient Clinics, São Paulo State University, UNESP, Botucatu 01049-010, Brazil
| | - Paulo Gustavo Kotze
- Colorectal Surgery Unit, Pontificia Universidade Católica do Paraná, PUCPR, Curitiba 80910-215, Brazil
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Karami H, Shirvani Shiri M, Ebadi Fard Azar F, Bagheri Lankarani K, Ghahramani S, Rezapour A, Tatari M, Heidari Javargi Z. Factors associated with health-related quality of life in patients with Crohn's disease in Iran: A prospective observational study. Front Med (Lausanne) 2023; 9:1091330. [PMID: 36760884 PMCID: PMC9907090 DOI: 10.3389/fmed.2022.1091330] [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: 11/06/2022] [Accepted: 12/30/2022] [Indexed: 01/20/2023] Open
Abstract
This was a 1-year prospective observational study of the health-related quality of life (HRQoL) of moderate to severe crohn's disease (CD) patients in Iran. Patients' HRQoL were measured using the EQ-5D 3L, EQ-VAS, and IBDQ-9 tools. HRQoL among CD patients were compared using the T-test, Mann-Whitney, Chi-square, and Fisher's exact tests. To discover factors influencing patients' HRQoL, multivariate linear regression and multivariate logistic regression tests were utilized. The study included 222 CD patients, with a mean age of 34.67 and mean disease duration of 7.32 years. The dimensions with the worst reported "relatively or extreme problems" were P/D: 77.5% and A/D: 63.1%. Employment, having "other chronic diseases," and ADA consumption were the most important independent predictors of HRQoL in CD patients, [β = 0.21 (EQ-5D index), β = 19.61 (EQ-VAS), β = 12.26 (IBDQ-9), OR: 0.09 (MO), OR: 0.12 (UA), OR: 0.21 (P/D), OR: 0.22 (A/D)], [β = -0.15 (EQ-5D index), β = -5.84 (IBDQ-9), β = -11.06 (EQ-VAS), OR: 4.20 (MO), OR: 6.50 (UA)], and [OR: 2.29 (A/D)], respectively. Unemployment, presence of "other chronic conditions" had the greatest negative impact on HRQoL of CD patients. There were significant differences in the probability of reporting "relatively or extreme problems" in the SC and A/D dimensions between patients using adalimumab (ADA) and infliximab (IFX).
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Affiliation(s)
- Hassan Karami
- Department of Economics, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Shirvani Shiri
- Department of Health Management and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Farbod Ebadi Fard Azar
- Health Promotion Research Center, Iran University of Medical Sciences, Tehran, Iran,*Correspondence: Farbod Ebadi Fard Azar ✉
| | - Kamran Bagheri Lankarani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Fars, Iran
| | - Sulmaz Ghahramani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Fars, Iran
| | - Aziz Rezapour
- Health Management and Economics Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Tatari
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran,Vice Chancellery of Health, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
| | - Zahra Heidari Javargi
- Department of Clinical Medicine, School of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
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Cassinotti A, Mezzina N, De Silvestri A, Di Paolo D, Lenti MV, Bezzio C, Stradella D, Mauri M, Zadro V, Ricci C, Casini V, Radice E, Massari A, Maconi G, Saibeni S, Caprioli F, Tari R, Fichera M, Cortelezzi CC, Parravicini M, Tinelli C, Testoni PA, Pace F, Segato S, Invernizzi P, Occhipinti P, Manes G, Di Sabatino A, Pastorelli L, Vecchi M, Ardizzone S. Continuous clinical remission with biologics in ulcerative colitis: the 'AURORA' comparison study. Eur J Gastroenterol Hepatol 2022; 34:1238-1246. [PMID: 36165081 DOI: 10.1097/meg.0000000000002443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR). METHODS In a retrospective, multicentre study, all UC patients treated with adalimumab, infliximab biosimilar, golimumab or vedolizumab between 2014 and 2019 were included. All drugs were compared to each other according to the 1-year CCR rate, defined as Mayo partial score ≤2, with bleeding subscore = 0, without any relapse or optimization with dose escalation, topical treatments or steroid use after first clinical remission. RESULTS Four-hundred sixteen patients (adalimumab = 90, infliximab biosimilar = 105, golimumab = 79, vedolizumab = 142) were included. CCR was achieved in similar percentages among the groups (33%, 37%, 28%, 37%, respectively). All drugs were equivalent in biologic-naive patients, while vedolizumab was better than a second anti-TNFα in prior anti-TNFα agent failures. No differences were found according to type of adverse events or severe adverse events. CONCLUSIONS Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year. Changing to vedolizumab is more effective than switching to another anti-TNFα in TNFα failures.
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Affiliation(s)
- Andrea Cassinotti
- Gastroenterology Unit, Department of Biochemical and Clinical Sciences "L. Sacco", University of Milan, ASST Fatebenefratelli Sacco, Milan
- Gastroenterology and Digestive Endoscopy Unit, ASST Sette Laghi, Varese
| | - Nicolò Mezzina
- Gastroenterology Unit, Department of Biochemical and Clinical Sciences "L. Sacco", University of Milan, ASST Fatebenefratelli Sacco, Milan
- Postgraduate School in Gastroenterology, University of Milan, Milan
| | | | - Dhanai Di Paolo
- Postgraduate School in Gastroenterology, University of Milan, Milan
- Gastroenterology Unit, Policlinico San Donato, San Donato Milanese
| | - Marco Vincenzo Lenti
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia
| | | | | | - Martina Mauri
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza
| | - Valentina Zadro
- Gastroenterology Unit, Department of Biochemical and Clinical Sciences "L. Sacco", University of Milan, ASST Fatebenefratelli Sacco, Milan
- Postgraduate School in Gastroenterology, University of Milan, Milan
| | - Chiara Ricci
- Gastroenterology Unit, ASST Spedali Civili Brescia, Brescia
| | | | | | - Alessandro Massari
- Gastroenterology Unit, Department of Biochemical and Clinical Sciences "L. Sacco", University of Milan, ASST Fatebenefratelli Sacco, Milan
| | - Giovanni Maconi
- Gastroenterology Unit, Department of Biochemical and Clinical Sciences "L. Sacco", University of Milan, ASST Fatebenefratelli Sacco, Milan
| | | | - Flavio Caprioli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano
| | - Roberto Tari
- Gastroenterology Unit, Ospedale Maggiore della Carità, Novara
| | - Maria Fichera
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza
| | | | - Marco Parravicini
- Gastroenterology and Digestive Endoscopy Unit, ASST Sette Laghi, Varese
| | - Carmine Tinelli
- Clinical Epidemiology and Biometry, Fondazione IRCCS Policlinico San Matteo, Pavia
| | | | - Fabio Pace
- Gastroenterology Unit, ASST Bergamo Est, Seriate
| | - Sergio Segato
- Gastroenterology and Digestive Endoscopy Unit, ASST Sette Laghi, Varese
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza
| | | | | | - Antonio Di Sabatino
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia
| | - Luca Pastorelli
- Gastroenterology Unit, Policlinico San Donato, San Donato Milanese
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Maurizio Vecchi
- Postgraduate School in Gastroenterology, University of Milan, Milan
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico
| | - Sandro Ardizzone
- Gastroenterology Unit, Department of Biochemical and Clinical Sciences "L. Sacco", University of Milan, ASST Fatebenefratelli Sacco, Milan
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Yin J, Li Y, Chen Y, Wang C, Song X. Adalimumab for induction of remission in patients with Crohn's disease: a systematic review and meta-analysis. Eur J Med Res 2022; 27:190. [PMID: 36175983 PMCID: PMC9523983 DOI: 10.1186/s40001-022-00817-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 09/12/2022] [Indexed: 11/17/2022] Open
Abstract
Purpose A large number of people with Crohn's disease (CD) fail to recover from conventional therapy or biological therapy. Some studies showed that adalimumab (ADA) may be an effective alternative therapy for these patients. The aim of this study was to evaluate the efficacy and safety of ADA in inducing CD remission. Methods We performed search of Pubmed/MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register, and several other databases. Randomized controlled trials (RCTs) comparing any dose of ADA with controls (placebo or active) in participants with active CD were included. The primary outcome was the failure to achieve clinical response/remission at 4 weeks. Several subgroup and sensitivity analyses were performed. Review Manager Software v5.3 was used. Results Four RCTs were included (n = 919), in which 553 participants received ADA and 366 participants received placebo. A meta-analysis of four studies showed that at 4 weeks, there were more people in the ADA group with clinical response/remission or symptom improvement compared with the placebo group. The rates of side effects, serious side effects, and study withdrawals due to side effects were lower in ADA participants than placebo ones. Conclusion This meta-analysis shows that ADA is superior to placebo in induction of clinical response/remission of CD patients, but no firm conclusions can be drawn on the safety of ADA in CD due to the low number of events. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s40001-022-00817-6.
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Affiliation(s)
- Juntao Yin
- Department of Pharmacy, Huaihe Hospital, Henan University, Kaifeng, Henan, China. .,Department of Pharmaceutics, School of Pharmacy, Henan University, Zhengzhou, 450000, Henan, China.
| | - Yang Li
- Department of Pharmacy, Huaihe Hospital, Henan University, Kaifeng, Henan, China
| | - Yangyang Chen
- Cardiology, Huaihe Hospital, Henan University, Kaifeng, Henan, China
| | - Chaoyang Wang
- General Surgery, Huaihe Hospital, Henan University, Kaifeng, 475000, Henan, China.
| | - Xiaoyong Song
- Department of Pharmaceutics, School of Pharmacy, Henan University, Zhengzhou, 450000, Henan, China
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Yang HH, Huang Y, Zhou XC, Wang RN. Efficacy and safety of adalimumab in comparison to infliximab for Crohn's disease: A systematic review and meta-analysis. World J Clin Cases 2022; 10:6091-6104. [PMID: 35949827 PMCID: PMC9254215 DOI: 10.12998/wjcc.v10.i18.6091] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 02/14/2022] [Accepted: 04/30/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Adalimumab (ADA) and infliximab (IFX) are the cornerstones of the treatment of Crohn’s disease (CD). It remains controversial whether there is a difference in the effectiveness and safety between IFX and ADA for CD.
AIM To perform a meta-analysis to compare the effectiveness and safety of ADA and IFX in CD.
METHODS PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Cohort studies were considered for inclusion. The primary outcomes were induction of response and remission, maintenance of response and remission, and secondary loss of response. Adverse events were secondary outcomes.
RESULTS Fourteen cohort studies were included. There was no apparent difference between the two agents in the induction response [odds ratio (OR): 1.27, 95% confidence interval (CI): 0.93-1.74, P = 0.14] and remission (OR: 1.11, 95%CI: 0.78–1.57, P = 0.57), maintenance response (OR: 1.08, 95%CI: 0.76–1.53, P = 0.67) and remission (OR: 1.26, 95%CI: 0.87–1.82, P = 0.22), and secondary loss of response (OR: 1.01, 95%CI: 0.65–1.55, P = 0.97). Subgroup analysis revealed ADA and IFX had similar rates of response, remission, and loss of response either in anti-tumor necrosis factor-α naïve or non-naïve patients. Further, there was a similar result regardless of whether CD patients were treated with optimized therapy, including dose intensification, shortening interval, and combination immunomodulators. However, ADA had a fewer overall adverse events than IFX (OR: 0.62, 95%CI: 0.42–0.91, P = 0.02).
CONCLUSION ADA and IFX have similar clinical benefits for anti-tumor necrosis factor-α naïve or non-naïve CD patients. Overall adverse events rate is higher in patients in the IFX group.
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Affiliation(s)
- Hua-Hua Yang
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yi Huang
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Xu-Chun Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Ruo-Nan Wang
- Department of Endocrinology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, Hubei Province, China
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Bronsky J, Copova I, Kazeka D, Lerchova T, Mitrova K, Pospisilova K, Sulovcova M, Zarubova K, Hradsky O. Adalimumab vs Infliximab in Pediatric Patients With Crohn's Disease: A Propensity Score Analysis and Predictors of Treatment Escalation. Clin Transl Gastroenterol 2022; 13:e00490. [PMID: 35363628 PMCID: PMC9132518 DOI: 10.14309/ctg.0000000000000490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 03/04/2022] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Two antitumor necrosis factor therapies (infliximab [IFX] and adalimumab [ADA]) have been approved for the treatment of pediatric Crohn's disease (CD) but have not been compared in head-to-head trials. The aim of this study was to compare the efficacy and safety of ADA and IFX by propensity score matching in a prospective cohort of pediatric patients with luminal CD and at least a 24-month follow-up. METHODS Among 100 patients, 75 met the inclusion criteria, and 62 were matched by propensity score. We evaluated time to treatment escalation as the primary outcome and primary nonresponse, predictors of treatment escalation and relapse, serious adverse events, pharmacokinetics, and effect of concomitant immunomodulators as secondary outcomes. RESULTS There was no difference between ADA and IFX in time to treatment escalation (HR = 0.63 [95% CI 0.31-1.28] P = 0.20), primary nonresponse (P = 0.95), or serious adverse events. The median (interquartile range) trough levels at the primary outcome were 14.05 (10.88-15.40) and 6.15 (2.08-6.58) µg/mL in the ADA and IFX groups, respectively. On a multivariate analysis, the combination of anti-Saccharomyces cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity was a strong independent predictor of treatment escalation (HR 5.19, [95% CI 2.41-11.18], P < 0.0001). The simple endoscopic score for CD, L3 disease phenotype, and use of concomitant immunomodulators for at least the first 6 months revealed a trend toward significance on a univariate analysis. DISCUSSION Propensity score matching did not reveal substantial differences in efficacy or safety between ADA and IFX. The anti-S. cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity combination is a strong predictor of treatment escalation.
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Affiliation(s)
- Jiri Bronsky
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Ivana Copova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Denis Kazeka
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Tereza Lerchova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Katarina Mitrova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
- IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic.
| | - Kristyna Pospisilova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Miroslava Sulovcova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Kristyna Zarubova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Ondrej Hradsky
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
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9
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Jung YS, Han M, Park S, Cheon JH. Comparison of Long-term Outcomes of Infliximab versus Adalimumab in 1,488 Biologic-Naive Korean Patients with Crohn's Disease. Gut Liver 2021; 15:92-99. [PMID: 32839359 PMCID: PMC7817934 DOI: 10.5009/gnl19377] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 12/07/2019] [Accepted: 12/15/2019] [Indexed: 12/17/2022] Open
Abstract
Background/Aims Data on the comparative effectiveness of infliximab (IFX) or adalimumab (ADA) in patients with Crohn’s disease (CD) are rare, particularly for Asian patients. We compared the key clinical outcomes (surgery, hospitalization, and corticosteroid use) of use of these two drugs in biologic-naive Korean patients with CD. Methods Using National Health Insurance claims, we collected data on patients who were diagnosed with CD and exposed to IFX or ADA between 2010 and 2016. Results We included 1,488 new users of biologics (1,000 IFX users and 488 ADA users). Over a median follow-up period of 2.1 years after starting biological therapy, no significant differences were found between IFX and ADA users in the risks for surgery (ADA vs IFX adjusted hazard ratio [aHR], 1.22; 95% confidence interval [CI], 0.81 to 1.84), hospitalization (aHR, 1.02; 95% CI, 0.81 to 1.28), and corticosteroid use (aHR, 0.82; 95% CI, 0.56 to 1.19). These results were unchanged even when only patients who used biologics for over 6 months were analyzed (aHR [95% CI] surgery, 1.31 [0.82 to 2.11]; hospitalization, 1.02 [0.80 to 1.30]; corticosteroid use, 0.80 [0.54 to 1.18]). Additionally, these results were unchanged in patients treated with biologics as monotherapy or in combination with immunomodulators. Conclusions In this nationwide population-based study, no significant difference was found in the long-term effectiveness of IFX and ADA in the real-world setting of biologic-naive Korean patients with CD. In the absence of trials to directly compare IFX and ADA, our study indicates that the selection of one of these two biologics can be determined by patient and/or physician preference.
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Affiliation(s)
- Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Minkyung Han
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Sohee Park
- Department of Biostatistics, Graduate School of Public Health, Yonsei University, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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10
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Tseng CH. Metformin Use Is Associated with a Lower Risk of Inflammatory Bowel Disease in Patients with Type 2 Diabetes Mellitus. J Crohns Colitis 2021; 15:64-73. [PMID: 32604412 DOI: 10.1093/ecco-jcc/jjaa136] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM Our aim was to compare the risk of developing inflammatory bowel disease [IBD] between ever users and never users of metformin. METHODS Patients with newly diagnosed type 2 diabetes mellitus from 1999 to 2005 were enrolled from Taiwan's National Health Insurance. A total of 340 211 ever users and 24 478 never users who were free from IBD on January 1, 2006 were followed up until December 31, 2011. Hazard ratios were estimated by Cox regression incorporating the inverse probability of treatment weighting using a propensity score. RESULTS New-onset IBD was diagnosed in 6466 ever users and 750 never users. The respective incidence rates were 412.0 and 741.3 per 100 000 person-years and the hazard ratio for ever vs never users was 0.55 [95% confidence interval: 0.51-0.60]. A dose-response pattern was observed while comparing the tertiles of cumulative duration of metformin therapy to never users. The respective hazard ratios for the first [<26.0 months], second [26.0-58.3 months] and third [>58.3 months] tertiles were 1.00 [0.93-1.09], 0.57 [0.52-0.62] and 0.24 [0.22-0.26]. While patients treated with oral antidiabetic drugs [OADs] without metformin were treated as a reference group, the hazard ratios for patients treated with OADs with metformin, with insulin without metformin [with/without other OADs] and with insulin and metformin [with/without other OADs] were 0.52 [0.42-0.66], 0.95 [0.76-1.20] and 0.50 [0.40-0.62], respectively. CONCLUSION A reduced risk of IBD is consistently observed in patients with type 2 diabetes mellitus who have been treated with metformin.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Zhunan, Taiwan
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11
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Han M, Jung YS, Cheon JH, Park S. Comparison of Real-World Outcomes of Infliximab versus Adalimumab in Biologic-Naïve Korean Patients with Ulcerative Colitis: A Population-Based Study. Yonsei Med J 2020; 61:48-55. [PMID: 31887799 PMCID: PMC6938779 DOI: 10.3349/ymj.2020.61.1.48] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 11/29/2019] [Accepted: 12/02/2019] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Data on the comparative effectiveness of infliximab (IFX) or adalimumab (ADA) in patients with ulcerative colitis (UC) are extremely limited, especially in the Asian population. We compared clinically important outcomes [colectomy, UC-related emergency room (ER) visits, UC-related hospitalizations, and need for corticosteroids] for these two biologics in biologic-naïve Korean patients with UC. MATERIALS AND METHODS Using National Health Insurance claims, we collected data on patients who were diagnosed with UC and exposed to IFX or ADA between 2010 and 2016. RESULTS A total of 862 new users of biologics were included, of whom 630 were treated with IFX and 232 were treated with ADA. Over a median follow-up of 1.8 years after starting biologic therapy, there were no significant differences in the risk of colectomy [adjusted hazard ratio (aHR), 1.87; 95% confidence interval (CI), 0.30-11.63], ER visits (aHR, 1.58; 95% CI, 0.79-3.16), hospitalizations (aHR, 0.83; 95% CI, 0.59-1.17), and corticosteroid use (aHR, 1.16; 95% CI, 0.76-1.78) between IFX and ADA users. These results were stable even when only patients who used biologics for ≥6 months were analyzed. Additionally, these results were unchanged in patients treated with biologic monotherapy or combination therapy with immunomodulators. CONCLUSION In this nationwide population-based study, there was no significant difference in the risk of colectomy, ER visits, hospitalizations, and corticosteroid use between IFX and ADA users. Our findings indicate that IFX and ADA have comparable effectiveness in biologic-naïve Korean patients with UC.
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Affiliation(s)
- Minkyung Han
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
| | - Sohee Park
- Department of Biostatistics, Graduate School of Public Health, Yonsei University, Seoul, Korea.
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12
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Singh S, Facciorusso A, Dulai PS, Jairath V, Sandborn WJ. Comparative Risk of Serious Infections With Biologic and/or Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2020; 18:69-81.e3. [PMID: 30876964 PMCID: PMC8011651 DOI: 10.1016/j.cgh.2019.02.044] [Citation(s) in RCA: 152] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 01/29/2019] [Accepted: 02/17/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We performed a systematic review and meta-analysis to evaluate the comparative risk of serious infections with tumor necrosis factor (TNF) antagonists, non-TNF targeted biologics, tofacitinib, and immunosuppressive agents in patients with inflammatory bowel diseases (IBDs). METHODS In a systematic search of publications, through March 18, 2018, we identified 15 observational studies (>500 person-years) of patients with IBD treated with TNF antagonists, non-TNF targeted biologics, tofacitinib, and/or immunosuppressive agents (thiopurines, methotrexate) that reported risk of serious infections. Only studies with active comparators were included, to allow appropriate comparative synthesis. We performed random-effects meta-analysis and estimated relative risk (RR) and 95% CIs. RESULTS Compared with anti-TNF monotherapy, risk of serious infection increased with the combination of anti-TNF and an immunosuppressive agent (in 6 cohorts: RR, 1.19; 95% CI, 1.03-1.37), with anti-TNF and a corticosteroid (in 4 cohorts: RR, 1.64; 95% CI, 1.33-2.03), or with all 3 drugs (in 2 cohorts: RR, 1.35; 95% CI, 1.04-1.77); there was minimal heterogeneity among studies. In contrast, monotherapy with an immunosuppressive agent was associated with a lower risk of serious infections than monotherapy with a TNF antagonist (7 cohorts: RR, 0.61; 95% CI 0.44-0.84) or a TNF antagonist with an immunosuppressive agent (2 cohorts: RR, 0.56; 95% CI, 0.39-0.81). Infliximab-based therapy was associated with a lower risk of serious infections compared with adalimumab-based therapy in patients with ulcerative colitis (4 cohorts: RR, 0.57; 95% CI, 0.33-0.97), but not Crohn's disease (4 cohorts: RR, 0.91; 95% CI, 0.49-1.70). Few data were available on the comparative safety of biologic agents that do not inhibit TNF and tofacitinib. CONCLUSIONS Combination therapies for IBD that include TNF antagonists, especially with corticosteroids, are associated with a higher risk of serious infection, whereas monotherapy with an immunosuppressive agent is associated with a lower risk, compared with monotherapy with a TNF antagonist. Studies are needed to evaluate the comparative safety of non-TNF targeted biologics and small molecules for treatment of IBD.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California.
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Parambir S. Dulai
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, University Hospital, Ontario, Canada,Division of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | - William J. Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California
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Bezzio C, Imperatore N, Armuzzi A, Rizzello F, Manes G, Bossa F, Calabrese E, Caprioli F, Daperno M, Mocciaro F, Orlando A, Papi C, Rispo A, Saibeni S. Barriers to anti‐TNFalpha prescription among Italian physicians managing inflammatory bowel disease. ACTA ACUST UNITED AC 2019. [DOI: 10.1002/ygh2.331] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Cristina Bezzio
- Gastroenterology Unit ASST Rhodense, Rho Hospital Milan Italy
| | - Nicola Imperatore
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine Federico II of Naples Naples Italy
| | - Alessandro Armuzzi
- IBD Unit Presidio Columbus Fondazione Policlinico A. Gemelli IRCCS ‐ Università Cattolica del Sacro Cuore Rome Italy
| | | | - Gianpiero Manes
- Gastroenterology Unit ASST Rhodense, Rho Hospital Milan Italy
| | - Fabrizio Bossa
- Division of Gastroenterology Casa Sollievo della Sofferenza Hospital, IRCCS San Giovanni Rotondo Italy
| | - Emma Calabrese
- Gastroenterology Department of Systems Medicine University of Rome Tor Vergata Rome Italy
| | - Flavio Caprioli
- Department of Pathophysiology and Transplantation University of Milan and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano Milan Italy
| | | | - Filippo Mocciaro
- UOC Gastroenterologia, ARNAS Ospedale Civico Palermo Palermo Italy
| | - Ambrogio Orlando
- Division of Internal Medicine 2 IBD Unit, Riuniti Villa Sofia‐Cervello Hospital Palermo Italy
| | | | - Antonio Rispo
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine Federico II of Naples Naples Italy
| | - Simone Saibeni
- Gastroenterology Unit ASST Rhodense, Rho Hospital Milan Italy
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