A systematic review and meta-analysis depicted that combining Tofacitinib with Methotrexate was more effective than using Methotrexate alone in active rheumatoid arthritis treatment. Yan Gao et al. aimed to assess the safety and effectiveness of Tofacitinib plus Methotrexate compared to Methotrexate alone.

To identify randomized clinical trials comparing Tofacitinib combined with Methotrexate versus Methotrexate monotherapy in rheumatoid arthritis, electronic databases such as EMBASE, Cochrane Library, PubMed, and Web of Science were explored by 2 reviewers. Data extraction and quality assessment of the included literature were performed, and RevMan 5.3 software was used for data analysis. The study followed the PRISMA guidelines.

The assessment measures included the occurrence of adverse events, erythrocyte sedimentation rate (ESR), Disease Activity Score 28 (DAS28), American College of Rheumatology (ACR) 70, ACR 50, and ACR 20. Out of 1152 studies initially identified, four trials involving a total of 1782 subjects (1345 receiving Tofacitinib + Methotrexate and 437 receiving Methotrexate alone) were included. In people having unsatisfactory responses to Methotrexate, the combination of Tofacitinib and Methotrexate showed significant advantages over Methotrexate monotherapy.

Tofacitinib combined with Methotrexate demonstrated higher response rates for ACR20, ACR50, and ACR70 compared to Methotrexate monotherapy. ACR20 (odds ratio [OR], 3.62), ACR50 (OR, 5.17), ACR70 (OR, 8.44), DAS28 (ESR) < 2.6 (OR, 4.71). The probability of adverse events was lower in the Tofacitinib + Methotrexate group than in the Methotrexate only group (OR, 1.42). Discontinuation rates because of lack of efficacy or adverse events were similar between the  groups (OR, 0.93).

The likelihood of experiencing abnormal liver enzymes was significantly lower with Tofacitinib + Methotrexate compared to Methotrexate alone (OR, 1.86). However, there were no substantial differences in cardiovascular illness, anemia, neutropenia, and severe adverse reactions between the two groups. Tofacitinib combined with Methotrexate could be an effective treatment option for refractory rheumatoid arthritis, considering its therapeutic efficacy and hepatoprotective properties. But, additional large-scale and high-quality trials are needed to confirm its hepatoprotective effects.