Carlos Alves1, Ana Penedones2, Diogo Mendes2, Francisco Batel Marques1. 1. From the Faculty of Pharmacy, University of Coimbra. 2. UFC-Coimbra Regional Pharmacovigilance Unit, CHAD-Centre for Health Technology Assessment and Drug Research, AIBILI-Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.
Abstract
BACKGROUND/ OBJECTIVE: The Janus kinases (JAKs) are cytoplasmic tyrosine kinases associated with membrane cytokine receptors that mediate signaling of multiple cytokines and growth factors, contributing to the pathogenesis of multiple autoimmune disorders. The JAK inhibitors are a new class of targeted therapies with proven efficacy in treating rheumatoid arthritis but are associated with an increased risk of infections. This study is aimed at comparing the relative safety of the different JAK inhibitors with regard to the risk of serious infections in patients with rheumatoid arthritis. METHODS: PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov were searched to identify randomized controlled trials evaluating the efficacy and safety of JAK inhibitors in patients with rheumatoid arthritis. The outcomes assessed were the risk of total and serious infections, tuberculosis, and herpes zoster. Sensitivity analysis disaggregated the results according to background therapy and licensed doses of JAK inhibitors. RESULTS: Thirty-seven randomized controlled trials that were included met the inclusion criteria. Compared with filgotinib, adalimumab (4.81; 95% confidence interval [CI], 1.39-16.66), etanercept (6.04; 95% CI, 1.79-20.37), peficitinib (7.56; 95% CI, 1.63-35.12), tofacitinib (4.29; 95% CI, 1.43-12.88), and upadacitinib (4.35; 95% CI, 1.46-13.00) have an increased risk of herpes zoster infection. Risk differences between the drugs became statistically nonsignificant when the sensitivity analysis was conducted. CONCLUSIONS: The risk of infections seems to be similar among the currently approved JAK inhibitor drugs. Although the initial results suggested that filgotinib could have a reduced risk of herpes zoster, the sensitivity analyses did not support those findings.
BACKGROUND/ OBJECTIVE: The Janus kinases (JAKs) are cytoplasmic tyrosine kinases associated with membrane cytokine receptors that mediate signaling of multiple cytokines and growth factors, contributing to the pathogenesis of multiple autoimmune disorders. The JAK inhibitors are a new class of targeted therapies with proven efficacy in treating rheumatoid arthritis but are associated with an increased risk of infections. This study is aimed at comparing the relative safety of the different JAK inhibitors with regard to the risk of serious infections in patients with rheumatoid arthritis. METHODS: PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov were searched to identify randomized controlled trials evaluating the efficacy and safety of JAK inhibitors in patients with rheumatoid arthritis. The outcomes assessed were the risk of total and serious infections, tuberculosis, and herpes zoster. Sensitivity analysis disaggregated the results according to background therapy and licensed doses of JAK inhibitors. RESULTS: Thirty-seven randomized controlled trials that were included met the inclusion criteria. Compared with filgotinib, adalimumab (4.81; 95% confidence interval [CI], 1.39-16.66), etanercept (6.04; 95% CI, 1.79-20.37), peficitinib (7.56; 95% CI, 1.63-35.12), tofacitinib (4.29; 95% CI, 1.43-12.88), and upadacitinib (4.35; 95% CI, 1.46-13.00) have an increased risk of herpes zoster infection. Risk differences between the drugs became statistically nonsignificant when the sensitivity analysis was conducted. CONCLUSIONS: The risk of infections seems to be similar among the currently approved JAK inhibitor drugs. Although the initial results suggested that filgotinib could have a reduced risk of herpes zoster, the sensitivity analyses did not support those findings.
Authors: Kevin L Winthrop; Peter Nash; Kunihiro Yamaoka; Eduardo Mysler; Nasser Khan; Heidi S Camp; Yanna Song; Jessica L Suboticki; Jeffrey R Curtis Journal: Ann Rheum Dis Date: 2021-10-06 Impact factor: 19.103
Authors: Maryam A Adas; Edward Alveyn; Emma Cook; Mrinalini Dey; James B Galloway; Katie Bechman Journal: Expert Rev Clin Immunol Date: 2021-12-29 Impact factor: 4.473