Withdrawal of MTX in rheumatoid arthritis patients on bDMARD/tsDMARD plus methotrexate at target: a systematic review and meta-analysis

Objectives To evaluate the effect of MTX withdrawal on disease activity and remission rate in patients at target after treatment with biologic DMARDs (bDMARDs)/targeted synthetic DMARDs (tsDMARDs) plus MTX. Material and methods We searched the PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials (RCTs) on MTX withdrawal in patients with RA at target after combination therapy from inception to 7 March 2022 in order to extract data, including: the change from withdrawal in DAS28 at the endpoint; proportion of low disease activity (LDA) assessed by DAS28, Simplified Disease Activity Index (SDAI) or Clinical Disease Activity Index (CDAI); proportion of remission assessed by DAS28, SDAI CDAI or ACR/EULAR Boolean remission. The Cochrane Q test and I-2 test were used to assess heterogeneity, and random-effects models were used for data synthesis. This study is registered with PROSPERO (CRD42022303891). Results Six articles were included for qualitative and quantitative analysis, all of which were noninferior RCTs involving 1430 patients (734 in the withdrawal group and 696 in the continuation group). Compared with continuing combination therapy, tapering off or discontinuing MTX increased DAS28 by 0.20 (95% CI 0.09, 0.32, I-2 = 0%) and decreased the percentage of patients with LDA assessed by DAS28 to <3.2 [risk ratio (RR) 0.88 (0.80, 0.97), I-2 = 0%]. However, MTX withdrawal did not decrease remission rates assessed by DAS28, SDAI, CDAI or ACR/EULAR Boolean remission [RR 0.90 (0.81, 1.01), 0.93 (0.77, 1.11), 0.90 (0.74, 1.11), 0.95 (0.70, 1.29), respectively]. Conclusions Withdrawing MTX slightly increases the RA disease activity in patients treated at target with bDMARDs/tsDMARDs plus MTX and has limited effects for patients with deep remission.