Rituximab and methotrexate in early RA: 2-year results

This study evaluates the outcomes associated with 2 years of treatment with rituximab + methotrexate versus methotrexate alone in rheumatoid arthritis patients. 

Rheumatoid arthritis (RA) is a chronic inflammatory disease that typically affects the small joints in the hands and feet. It is an autoimmune disorder, meaning that the immune system attacks the body’s own cells. Early treatment of the disease aims for remission (period of recovery) or establishing low disease activity (reduction in signs and symptoms).

B cells are white blood cells of the immune system. Their excessive production and survival is believed to be associated with the development of RA. B cell depletion with rituximab (Rituxan) is an established treatment for RA. When combined with methotrexate (Rheumatrex; inhibits the metabolism of folic acid), it has been shown to significantly reduce disease activity. A previous 1-year study showed that this combination of drugs inhibited progression of joint damage and improved clinical outcomes and physical function compared to methotrexate alone. This study evaluated the outcomes after 2 years of the same study. 

606 patients with RA participated in this study. The patients were randomly assigned to one of three groups: 2x500mg rituximab + methotrexate, 2x1000mg ritixumab + methotrexate and placebo + methotrexate.

At week 104 the 2x1000mg dose continued to inhibit progressive joint damage by 79% compared to placebo. The total erosion score (number of bone erosions present in affected joints, according to imaging scans) continued to be significantly lower in the 2x1000mg group (0.23) compared to the placebo group (1.32). A positive effect on joint space narrowing scores (measurement of the space between the bones in a joint, indicating cartilage deterioration) was observed in the 2x1000mg group (0.18) compared to the placebo group (0.63).

Progressive joint damage was also reduced in the 2x500mg group by approximately 61% compared to placebo. Erosive progression was also slower in this group (0.5) compared to placebo.

57% of patients receiving 2x1000mg of rituximab showed no radiographic progression (worsening of joint damage as assessed by radiography) versus 37% of the placebo group. Similarly, 49% of the 2x500mg group showed no radiographic progression versus 37% of the placebo group. Across both of the rituximab groups, 82% of patients with no radiographic progression at week 52 maintained this advantage at week 104 versus 64% of the placebo group.

A larger proportion of patients in the 2x500mg group (39%) and the 2x1000mg group (40%) achieved a 70% improvement in joint tenderness and joint swelling compared with the placebo group (22%).

45% of the 2x500mg group and 48% of the 2x1000mg group achieved low disease activity compared with 25% in the placebo group. 34% of the 2x500mg group and 32% of the 2x1000mg group achieved disease remission compared to 13% of the placebo group.

The safety profile of rituximab + methotrexate was similar to that of placebo + methotrexate. Withdrawals due to adverse events were low: 3% in both rituximab groups compared to 7% in the placebo group. 

Treatment with rituximab 2x1000mg + methotrexate is associated with significant reductions in radiographic progression and erosion score over 2 years of treatment. It is also associated with a higher likelihood of achieving disease remission and low disease activity. 

The study was not powered to compare outcomes between rituximab doses.