Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies.

OBJECTIVE: To determine if treatment with a B cell-targeted therapy can inhibit the progression of structural joint damage in patients with rheumatoid arthritis (RA), exhibiting an inadequate response to tumour necrosis factor (TNF) inhibitors. METHODS: In this phase III study, patients with an inadequate response to a TNF inhibitor and receiving methotrexate were randomised to rituximab or placebo. Radiographs were obtained at baseline, week 24 and week 56 after randomisation. Patients with an inadequate response to their randomised therapy could receive rescue medication from week 16. From week 24, eligible patients from both treatment arms could receive open-label rituximab. Patients were analysed according to their original treatment group. Radiographs were scored using the Genant-modified Sharp method. The primary radiographic endpoint was change in total Genant-modified Sharp score at week 56. RESULTS: Rituximab treatment caused significant reduction in joint damage progression compared with placebo. The mean change from baseline in the total Genant-modified Sharp score at week 56 was significantly lower for patients treated with rituximab than for patients treated with placebo (1.00 vs 2.31; p = 0.005), and was supported by changes in erosion score (0.59 and 1.32 for rituximab plus methotrexate vs placebo plus methotrexate, respectively; p = 0.011) and joint space narrowing score (0.41 and 0.99, respectively; p<0.001). CONCLUSIONS: This study provides the first evidence that a B cell-targeted therapy-rituximab-can significantly inhibit the progression of structural joint damage in patients with RA with long-standing, active and treatment-resistant disease.

Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy.

OBJECTIVE: To assess the effects of treatment with rituximab plus methotrexate on patient-reported outcomes in patients with active rheumatoid arthritis (RA) who experienced inadequate response to anti-tumor necrosis factor therapy. METHODS: Patients with active RA were randomly assigned to rituximab (1,000 mg on days 1 and 15) or placebo. The primary end point was the proportion of patients with an American College of Rheumatology 20% response at week 24. Additional goals were to assess treatment effects on pain, fatigue, functional disability, health-related quality of life, and disease activity by comparing mean changes between groups. The analysis was conducted in the intent-to-treat population. The proportion of patients who achieved the minimum clinically important difference on the Health Assessment Questionnaire (HAQ) disability index (DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Short Form 36 (SF-36) was determined. RESULTS: Rituximab patients had statistically significantly greater pain relief. The FACIT-F showed significantly greater improvement in rituximab patients than placebo patients from weeks 12 through 24. Mean improvement from baseline in functional disability (measured by the HAQ DI) was significantly greater in rituximab patients from weeks 8 to 24. The mean +/- SD change from baseline for the SF-36 Physical Component Score was 6.64 +/- 8.74 for rituximab patients and 1.48 +/- 7.32 for placebo patients (P < 0.0001). The mean change from baseline for the SF-36 Mental Component Score was 5.32 +/- 12.41 for rituximab patients and 2.25 +/- 12.23 for placebo patients (P = 0.0269). CONCLUSION: Rituximab produced rapid, clinically meaningful, and statistically significant improvements in patient-reported pain, fatigue, functional disability, health-related quality of life, and disease activity. These effects were sustained throughout the study.