Combo Methotrexate and Leflunomide Safety in RA Save

Methotrexate and leflunomide (LEF) are the most widely prescribed DMARDs worldwide; yet biologic DMARDs are the newest and best selling agents for rheumatoid arthritis worldwide. A recent study of combination therapy with MTX and LEF underscores the efficacy and safety of this approach and puts it in perspective against biologic DMARDs in RA.

The BiobadaBrasil registry was used to study RA patients starting a csDMARD (without previous use of bDMARD or JAKi) or their first bDMARD/JAKi.  They assessed those patients initiating combination MTX+LEF and compared outcomes to those starting csDMARDs, bDMARDs, or Janus kinase inhibitors (JAKi). Safety outcomes were primary in this analysis, including serious adverse events (SAEs) and serious infections (SIEs).

From the 1671 RA patients enrolled, 452 patients received MTX + LEF.

The overall incidence of SAEs was 5.6 per 100 PY.  Patients treated with combination MTX+LEF had better safety outcomes compared to other agents:

• MTX + LEF SAEs were not higher than with monotherapy with MTX or LEF (adjusted HR 1.00, 95% CI 0.76–1.31, P = 0.98).
• MTX + LEF had fewer SAEs than bDMARDs/JAKi with MTX or LEF (aHR 0.56, 0.36–0.88, P = 0.01).
• MTX + LEF had fewer SIEs than bDMARDs/JAKi with MTX or LEF (aHR 0.48, 0.25–0.94, P = 0.03) than 
• MTX + LEF had fewere SAEs than MTX + sulfasalazine (aHR 0.33, 0.16–0.65, P = 0.002). 

Overall, the safety of MTX + LEF in RA, may make this an attractive treatment option compared to the use of other regimens that may include MTX + SSZ, bDMARDs or JAKi.