Leflunomide, an FDA approved DMARD which helps to inhibit T-cell proliferation among patients with active rheumatoid arthritis. A randomised, double-blind controlled clinical trial was conducted which reflects leflunomide efficacy and safety and was as efficacious as rituximab which is a former RA treatment drug.

The standard dose of rituximab which is generally used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that a low dose i. e. 500 mg of rituximab is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide was unknown. In a tertiary care referral setting, a randomised, double-blind controlled clinical trial was conducted to compare the safety andefficacy of low-dose rituximab-methotrexate combination with the leflunomide-methotrexate combination.

Patients on 10-20 mg/week methotrexate with a Disease Activity Score (DAS) > 3.2 were randomly allocated to rituximab 500 mg on days 1 and 15 or leflunomide 10-20 mg/day. The primary end-point for the study was ACR20 response at 24 weeks. The sample of 40 had 70% power to detect a 30% difference. ACR50, ACR70, DAS, EULAR good response, CD3 + (T cell), CD19 + CD27+ (memory B cell) and CD19 + (B cell) counts, pneumococcal and tetanus antibody levels were secondary endpoints.

Baseline characteristics were comparable in the both groups. At week 24, ACR20 was 85% vs 84% with p = 0.93, ACR50 was 60% vs. 64% with p = 0.79 and ACR70 was 35% vs 32% with P = 0.84, in rituximab and in leflunomide groups respectively. Serious adverse events were similar. With rituximab there was significant reduction in B cells (p < 0.001), memory B cells (p < 0.001) and pneumococcal antibody levels (P < 0.05) without significant changes in T cells (p = 0.835) and tetanus antibody levels (p = 0.424) at 24 weeks. With leflunomide, significant reduction in memory B cells (p < 0.01) and pneumococcal antibody levels (p < 0.01) occurred without significant changes in B cells (P > 0.05), T cells (P > 0.05) or tetanus antibody levels (P > 0.05).

The combination of Leflunomide-methotrexate is as efficacious as the low-dose rituximab-methotrexate combination at 24 weeks, in RA patient's refractory to initial DMARDs. The high responses seen in both groups have favourable cost implications for patients in developing countries. Changes in immune parameters with leflunomide are novel and need further characterisation.