Comparative efficacy and safety of TNF-inhibitor plus methotrexate versus oral triple therapy in patients with active rheumatoid arthritis inadequately responding to methotrexate: A meta-analysis of randomized controlled trials

Aims: The study aimed to assess the efficacy and safety of tumor necrosis factor inhibitor (TNFI) with methotrexate (MTX) vs. oral triple therapy in patients with active rheumatoid arthritis (RA), showing inadequate response to MTX. Materials and methods: We performed a meta-analysis of three randomized controlled trials (RCTs) (913 MTX-resistant RA patients) to examine the relative efficacy and safety of TNFI-MTX compared to triple therapy (hydroxychloroquine, sulfasalazine, MTX) in patients with RA responding inadequately to MTX. Results: The American College of Rheumatology's 70% improvement (ACR70) response rate was significantly higher for TNFI-MTX patients than for triple therapy-treated controls (RR 1.549, 95% confidence interval (CI) 1.087 - 2.207, p = 0.016). However, the ACR20 and ACR50 response rates did not differ between the TNFI-MTX group and the triple therapy group. The total Sharp score was significantly lower in TNFI-MTXtreated patients than in triple therapy-treated controls (SMD -0.173, 95% CI -0.301 to -0.045, p = 0.008). There was no significant difference related to the number of patients with serious adverse events between the TNFI-MTX group and the triple therapy group (RR 1.033, 95% CI 0.710 - 1.504, p = 0.864); however, TNFI-MTX resulted in higher infection rates than triple therapy (RR 1.513, 95% CI 1.149 - 1.992, p = 0.004). Conclusion: TNFI-MTX was found to be more effective than triple therapy in active RA patients inadequately responsive to MTX, but it is associated with a higher risk of infection.