Objective: To evaluate the efficacy and safety of three dosing and repeat treatment regimens of rituximab (RTX) plus MTX in patients with active RA.
Methods: Patients with active RA despite stable MTX (10-25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 x 500 and 2 x 500 mg; 2 x 500 and 2 x 1000 mg (dose escalation); and 2 x 1000 and 2 x 1000 mg. The primary endpoint was proportion of patients achieving ACR20 at Week 48.
Results: At Week 48, ACR20 responses were not statistically significantly different between the dose regimens. Compared with RTX 2 x 500 mg (n = 134) or dose escalation (n = 119), ACR and European League Against Rheumatism (EULAR) outcomes in the RTX 2 x 1000 mg group (n = 93) were consistently higher, with significantly more patients achieving EULAR responses (P = 0.0495). At Week 48, rituximab 2 x 1000 mg was associated with a higher proportion of patients who, following retreatment, maintained or improved their Week 24 responses. Dose escalation from 2 x 500 to 2 x 1000 mg did not appear to be associated with improved outcomes compared with continual 2 x 500 mg. All RTX regimens demonstrated comparable safety.
Conclusions: RTX 2 x 500 and 2 x 1000 mg could not be clearly differentiated, although some efficacy outcomes suggest improved outcomes in the rituximab 2 x 1000 mg group. Retreatment from Week 24 resulted in a sustained suppression of disease activity through to Week 48.
Trial registration: ClinicalTrials.gov NCT00422383.