Efficacy and safety of non-conventional synthetic disease-modifying antirheumatic drugs in early active rheumatoid arthritis: a network meta-analysis

Abstract

Objective: To compare the clinical efficacy and safety of biological disease-modifying antirheumatic drugs (DMARDs) and Janus kinase(JAK) inhibitors in patients with early rheumatoid arthritis (RA). Methods: A systematic search was conducted of PubMed, Web of Science, Cochrane Library, and EMBASE databases (up to February 2025), supplemented by searches of clinical trial registries. Eligible randomised controlled trials enrolled adults with early RA (< 2 years) treated with biological DMARDs/JAK inhibitors versus conventional synthetic DMARDs. Statistical analyses were conducted using Stata software (version 16.0). Results: 21 eligible trials involving nine interventions and 8,361 participants were included in this meta-analysis. Multiple biological DMARDs demonstrated superior therapeutic efficacy compared to methotrexate. Adalimumab + methotrexate showed the most pronounced effect on DAS28 remission (OR 2.90[95% CI 1.94–4.33]; SUCRA 83.7%), while tocilizumab + methotrexate exhibited the highest efficacy in achieving ACR70 response (OR 4.41[95% CI 2.29–8.49]; SUCRA 94.7%). Regarding safety, only tocilizumab + methotrexate demonstrated a higher incidence of adverse events(OR 5.11[95% CI 2.03–12.86]; SUCRA 0.6%). No safety risks were identified for other interventions. Due to the limited number of eligible clinical trials, the optimal treatment strategy remains inconclusive. Conclusion: For patients with early RA and high disease activity, combination therapy with certain biological DMARDs demonstrated superior clinical efficacy compared to methotrexate. No noteworthy safety risks have been observed. More high-quality trials should be conducted to evaluate treatment strategies for individuals with early RA comprehensively. Clinical trial number: Not applicable