Comparative effectiveness of rituximab in combination with either methotrexate or leflunomide in the treatment of rheumatoid arthritis.

Objective: To compare the effectiveness and safety of a combination of rituximab (RTX) with either methotrexate (MTX) or leflunomide (LEF) in the treatment of patients with active rheumatoid arthritis (RA) and inadequate response to anti-tumor necrosis factor agents or traditional disease-modifying antirheumatic drugs (DMARD) in a real-world setting.

Methods: Data from 77 consecutive unselected patients with active RA and treated with at least 1 cycle of RTX (1 g × 2 weeks) plus MTX or LEF were retrospectively collected. A comparative study between the 2 combinations of treatment (RTX+MTX and RTX+LEF) was performed at 6 months of follow-up considering 3 outcomes: the improvement of RA disease activity, the evolution of functional disability, and the tolerability and side effect profile.

Results: Of the 77 patients, 45 received RTX+MTX and 32 RTX+LEF. At baseline there were no significant differences between the groups in terms of the main clinical and laboratory data, or in the number of previous DMARD and anti-tumor necrosis factor agents used. At 6 months of follow-up, we did not find significant differences between the 2 combinations in the evolution of RA disease activity (DAS28 response, according to the European League Against Rheumatism (EULAR) improvement criteria) and functional disability progression (health assessment questionnaire) over time. Minor adverse events occurred in 9% of RTX+MTX patients and in 9% of RTX+LEF patients. None of the patients had serious adverse events and none discontinued the treatment during the study period.

Conclusions: Our preliminary data support the view that LEF is a useful alternative if MTX is contraindicated, since its effectiveness and safety seem similar.