Comparative effectiveness of Janus kinase inhibitors and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis patients with an inadequate response to tumour necrosis factor alpha inhibitors: a network meta-analysis

Abstract

Introduction: Tumour necrosis factor alpha inhibitor (TNFi) was the first class of biologic disease-modifying antirheumatic drugs (bDMARDs) available for the treatment of rheumatoid arthritis (RA). Therefore, many studies have compared the efficacies of other bDMARDs and Janus kinase (JAK) inhibitors in patients with an inadequate response to TNFi. However, head-to-head comparisons among other bDMARDs and JAK inhibitors are lacking. Therefore, we conducted a network meta-analysis to compare the efficacies of bDMARDs and JAK inhibitors in patients with an inadequate response to TNFi. Methods: We searched literature using Medline, clinicaltrials.gov, and Embase. For inclusion, randomised controlled trials must include RA patients with an inadequate response to TNFi and report the proportion of patients who achieved ACR20 response in week 12/24. Results were analysed using R version 3.5.1 with ‘netmeta’ 4.9-2. Odds ratio (OR) and 95% confidence interval (CI) were estimated using random-effects model. Results: Twelve trials were included in this analysis. Tocilizumab was superior to other bDMARDs and JAK inhibitors in ACR20 response (OR=0.39, 95% CI=0.20-0.78 for abatacept; 0.26 (0.12-0.54) for baricitinib; 0.30 (0.14-0.64) for filgotinib 100 mg; 0.44 (0.21-0.93) for filgotinib 200 mg; 0.28 (0.13-0.61) for golimumab; 0.48 (0.24-0.99) for rituximab; 0.27 (0.13-0.53) for sarilumab; 0.22 (0.10-0.49) for tofacitinib; and 0.47 (0.22-0.98) for upadacitinib. Tocilizumab remained superior to baricitinib (0.28 [0.09-0.81]), filgotinib 100 mg (0.26 [0.09-0.71]), and sarilumab (0.32 [0.12-0.83]) in ACR50 response. Tocilizumab was superior to upadacitinib in ACR70 response (0.17 [0.03-0.90]). Conclusion: All bDMARDs and JAK inhibitors have comparable efficacies in RA patients with an inadequate response to TNFi. However, tocilizumab is better than other bDMARDs and JAK inhibitors in terms of ACR20 response.