Patients were given intravenous rituximab 1 g on days 1 and 15, and after 26 weeks if they responded to treatment but had persistent disease activity (28 joint count disease activity score [DAS28-ESR] >3.2; rituximab group) or a TNF inhibitor—adalimumab (40 mg subcutaneously every other week) or etanercept (50 mg per week subcutaneously) according to the patient's and rheumatologist's choice (TNF inhibitor group).
In a related editorial, the authors discuss the design and the findings of this study, highlighting certain limitations. The authors state that information about the baseline characteristics of the patients recruited in the trial was limited (such as the number of previous disease modifying anti-rheumatic drugs), which makes their representativeness for patients in daily practice difficult to assess.
Additionally, about 25% of both groups were methotrexate intolerant, which has greater consequences for the patients given TNF inhibitors than for the rituximab group because TNF inhibitors are less effective as monotherapy than in combination with methotrexate whereas data from observational studies suggest that the effectiveness of rituximab in addition to methotrexate is not clearly more effective than rituximab monotherapy.
The authors of the study also note that the European Medicines Agency (EMA) had previously rejected the application to extend the licence of rituximab to patients with rheumatoid arthritis who had not been given biologicals before, because of the reports of progressive multifocal leukoencephalopathy associated with rituximab, and therefore, formally, rituximab as a first option is a “non-approved” indication. A non-approved indication is legally different from off-label use and what the consequences are for prescribing a drug for which the indication was rejected by the EMA is unclear.