Evaluating leflunomide and methotrexate combination vs. monotherapy in rheumatoid and psoriatic arthritis.

Background/aim: Methotrexate (MTX) and leflunomide (LEF) are conventional synthetic disease-modifying antirheumatic drugs (DMARDs) commonly used for treating rheumatoid arthritis (RA) and psoriatic arthritis (PsA), either as monotherapies or in combination. This study aimed to compare the adverse effects (AEs) and efficacy of combined use of MTX plus LEF with monotherapy in RA and PsA patients. Materials and methods: This study included 528 patients (385 RA and 143 PsA) with at least 6 months of follow-up. Disease activity was assessed using DAS-28 CRP and DAPSA, and treatment-related AEs were classified based on specific MedDRA categories. Results: The cumulative incidence of AEs in patients with RA treated with MTX, LEF, and MTX plus LEF was 23.8%, 28.2%, and 19.2%, respectively; in PsA patients, 18.1%, 30%, and 23.3%, respectively. None of the groups were superior to each other in terms of general AEs between monotherapy and in combination. LEF monotherapy in RA was associated with more neurological AEs and hypertension. Compared to monotherapy, MTX plus LEF demonstrated greater reductions in disease activity, a more substantial decrease in glucocorticoid doses, and lower utilization of biological/targeted DMARDs (b/tsDMARDs) in both RA and PsA. In univariate analysis, MTX dosage, initial DAS28 CRP, and b/tsDMARD initiation were predictors of low disease activity (LDA) in RA. In multivariate analysis, MTX dosage (95% CI 1.02-1.59, OR = 1.27, p = 0.031) and initial DAS28-CRP (95% CI 2.14-10.90, OR = 4.38, p < 0.001) were found to be independently associated with LDA in RA. In PsA, the factors associated with LDA were initial DAPSA and disease duration in univariate analysis. Only disease duration was found to be an independent predictor in multivariate analysis (95% CI, 1.02-1.38, OR = 1.17 p = 0.039). Conclusion: Adding LEF to MTX or vice versa may serve as a valuable, safe, and effective alternative in situations where b/tsDMARD therapy is challenging.