The results from a randomized, double-blind controlled clinical trial showed that Leflunomide-methotrexate combination is as efficacious as the low-dose rituximab-methotrexate combination at 24 weeks, in RA patient's refractory to initial DMARDs.

Rheumatoid Arthritis is a systemic inflammatory condition resulting in joint damage with reduced locomotion. The standard dose of rituximab prescribed for rheumatoid arthritis (RA) is 1000 mg. But certain current studies showed that a low dose of rituximab (500 mg) is also effective. The efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic DMARDs, compared to leflunomide was unknown.

Thus, a clinical trial was conducted to compare the efficacy and safety of low-dose rituximab-methotrexate combination with the leflunomide-methotrexate combination.
In the current study patients on methotrexate (10-20 mg/week) with a Disease Activity Score (DAS) > 3.2 were randomly provided rituximab (500 mg on days 1 and 15) or leflunomide (10-20 mg/day). The primary end-point was ACR20 at 24 weeks. A sample of 40 had 70% power to detect a 30% difference. The secondary endpoints were ACR50, ACR70, DAS, EULAR good response, CD3 + (T cell), CD19 + (B cell) and CD19 + CD27+ (memory B cell) counts, pneumococcal and tetanus antibody levels.
The findings showed that baseline characteristics were comparable in the two groups. At week 24, ACR20 was 85% vs 84%, ACR50 was 60% vs. 64% and ACR70 was 35% vs 32%, in rituximab and in leflunomide groups respectively. SAEs were similar. But with rituximab, there was a significant reduction in B cells, memory B cells and pneumococcal antibody levels without significant changes in T cells and tetanus antibody levels at 24 weeks. With leflunomide, a significant reduction in memory B cells and pneumococcal antibody levels occurred without significant changes in B cells, T cells or tetanus antibody levels.

Changes in immune response parameters with leflunomide are novel and need further characterisation.