Comparative effectiveness and safety of non-tumour necrosis factor biologics and Janus kinase inhibitors in patients with active rheumatoid arthritis showing insufficient response to tumour necrosis factor inhibitors: A Bayesian network meta-analysis of randomized controlled trials

Abstract

What is known and objective: Both biologic and Janus kinase (JAK) inhibitor therapies have demonstrated substantial effectiveness in placebo-controlled studies in patients with active rheumatoid arthritis (RA) showing inadequate responses to tumour necrosis factor (TNF) inhibitors. The purpose of this study was to determine the relative effectiveness and safety of non-TNF biologics and JAK inhibitors in patients with RA showing insufficient response to TNF inhibitors.

Methods: A Bayesian network meta-analysis incorporating direct and indirect data from randomized controlled trials (RCTs) was used to investigate the effectiveness and safety of non-TNF biologics (abatacept, rituximab, tocilizumab, salirumab and sirukumab) and JAK inhibitors (tofacitinib, baricitinib, upadacitinib and filgotinib) in patients with RA showing insufficient response to TNF inhibitors.

Results: Nine RCTs, evaluating 3577 patients for 12 weeks fulfilled the inclusion requirements. JAK inhibitors and non-TNF biologics achieved a significant American College of Rheumatology 20% (ACR20) response relative to the placebo. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) showed that JAK inhibitor treatment was most likely to achieve the highest ACR20 response rate, followed by non-TNF biologics and placebo. The ACR50 rate displayed similar patterns as the ACR20 response rate, but non-TNF biologics have a higher value than JAK inhibitors based on the ACR70 response rate. Adverse events did not reach statistical significance nor did serious adverse events when looking at safety over 12 weeks. The confidence intervals overlap, and there is no clinical significance to these safety data, even compared with placebo.

What is new and conclusion: Both non-TNF biologics and JAK inhibitors have similar effects in patients with active RA that are refractory to anti-TNF treatment, and there were no differences with regard to safety among the treatments.

Keywords: JAK inhibitors; network meta-analysis; non-TNF biologics; rheumatoid arthritis.