Methotrexate–leflunomide combo safe in rheumatoid arthritis

Methotrexate (MTX) plus leflunomide (LEF) demonstrates a relatively good safety profile overall compared with the combination of MTX and sulfasalazine (SSZ) and strategies involving advanced therapies in rheumatoid arthritis (RA), reports a study.

A team of investigators evaluated the safety of MTX plus LEF in RA and compared it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease-modifying antirheumatic drugs (DMARDs) or Janus kinase (JAK) inhibitors. They followed RA patients on a treatment course with a csDMARD (without previous use of bDMARD or JAK inhibitor) or their first bDMARD/JAK inhibitor in a registry-based, multicentric cohort study in Brazil.

The incidence of serious adverse events and serious infections were the primary and secondary outcomes, respectively. Statistical comparisons were carried out through multivariate Cox proportional hazards models and propensity-score matching analysis (PSMA).

A total of 1,671 patients (5,349 patient-years) were included in the analysis, of whom 452 (1,537 patient-years) received the MTX–LEF combination. The overall incidence of serious adverse events was 5.6 per 100 patient-years.

The risk of serious adverse events for MTX plus LEF was not higher compared to MTX or LEF alone (adjusted hazard ratio [AHR], 1.00, 95 percent confidence interval [CI], 0.76–1.31; p=0.98). MTX plus LEF also had a lower risk of serious adverse events (AHR, 0.56, 95 percent CI, 0.36–0.88; p=0.01) and infectious serious adverse events (AHR, 0.48, 95 percent CI, 0.25–0.94; p=0.03) than bDMARDs or JAK inhibitors with MTX or LEF.

In addition, the MTX–LEF combination demonstrated a lower risk of serious adverse events than MTX plus SSZ (AHR, 0.33, 95 percent CI, 0.16–0.65; p=0.002).

Results obtained with traditional multivariate Cox analysis were confirmed in PSMA.