Tumor necrosis factor-alpha inhibitor combined with methotrexate for ankylosing spondylitis: a systematic review and meta-analysis

To evaluate the benefits and harms of combination of tumor necrosis factor-alpha (TNF-α) inhibitor and methotrexate (MTX) compared with TNF-α inhibitor monotherapy in the treatment of ankylosing spondylitis (AS). Randomized controlled trials were identified from Medline, Embase, Cinahl, Central and Clinical Trials Registry Platform, as well as from the reference sections of retrieved articles. The risk of bias was evaluated in all included trials. Data were extracted by two reviewers independently using a specially designed extraction form. The Cochrane Collaboration’s Review Manager 5.2 software was used for data analysis. The search retrieved 852 titles, of which 3 original trials were included, involving 187 participants. The overall risk of bias is low in all three trials. Only one study was placebo controlled, and all of them examined small samples. The analysis showed no significant advantage of the MTX combination versus monotherapy. Two trials assessed Assessment of Ankylosing Spondylitis (ASAS) 40 and the pooled risk ratio (RR) was 1.37 and 95% confidence interval 0.84 to 2.23. The RR for ASAS20 was 1.16 (0.88 to 1.52). Likewise, there were no significant difference between two groups in partial remission, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Magnetic resonance imaging activity score and other secondary outcomes. Withdrawals for side effects and for any reason were similar in two groups, RR were 1.89 (0.71 to 5.02) and 1.11 (0.67 to 1.84), respectively. The evidence available did not support any benefit of adding MTX to TNF-α inhibitor for the treatment of AS.