Systematic review: infections with JAK inhibitors

Abstract

In patients with rheumatoid arthritis, the risk of infections appears to be similar among all approved Janus kinase (JAK) inhibitors, according to the results of a systematic review and meta-analysis reported in the Journal of Clinical Rheumatology, although there may be an increased risk of herpes zoster infections with tofacitinib compared with filgotinib. The study involved searching PubMed, Embase, clinicaltrials.gov and the Cochrane library to identify 37 phase II-III clinical trials published in English where JAK inhibitors were compared with placebo, active DMARD treatment, or no treatment. The total infection risk was not observably different between JAK inhibitors. However, compared with placebo there was a significantly increased risk with tofacitinib, upadacitinib, adalimumab and methotrexate. When the probability of a treatment being the best alternative was ranked using the surface under the cumulative ranking curve (SUCRA) score, placebo was probably the safest treatment, followed by peficitinib and baricitinib. When results were restricted to those in patients receiving JAK inhibitors associated with conventional synthetic DMARDs, there were significant differences for placebo versus adalimumab, methotrexate, Pf-06650833, baricitinib and upadacitinib. Similarly, there were no observable differences in the risk of serious infections. By SUCRA score, peficitinib was probably the safest treatment, followed by placebo and Pf-06650833. No between-treatment differences were observed for tuberculosis. By SUCRA score, baricitinib was probably the safest treatment, followed by methotrexate and upadacitinib. Compared with filgotinib, the risk of herpes zoster infection was increased with adalimumab, etanercept, peficitinib, tofacitinib and upadacitinib. By SUCRA score, filgoitinib was probably the safest treatment, followed by placebo and baricitinib. When results were restricted to licensed doses of JAK inhibitors, there were significant differences for placebo versus etanercept and for filgotinib versus tofacitinib, etanercept or adalimumab. Postmarketing pharmacovigilance evidence will be of utmost importance in the assessment of the comparative risk of serious infections between JAK inhibitors , note the authors.