Infectious complications of long-term rituximab therapy for rheumatoid arthritis; an interim analysis

OBJECTIVE: To investigate whether prolonged rituximab use, defined as =5 courses, is associated with the use of more antimicrobial agents than short-term rituximab use in patients with rheumatoid arthritis (RA). The secondary study question was to find out whether prolonged rituximab use is associated with more self-reported infections than short-term rituximab use in RA patients. DESIGN: Prospective multicentre cohort study emanating from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. METHODS: All RA patients using rituximab in 2 × 1000 mg courses could be included. Inclusion for the interim analysis was from September 2010 until May 2012. Antimicrobial agents use was obtained from pharmacy records and was expressed as defined daily doses (DDD) per 100 patient days. Self-reported infections were inquired through a questionnaire. If more infections were present during an overlapping period, one infection was scored. RESULTS: 49 patients using rituximab were included, of which 11 used 5 or more courses. Use of 5 or more courses rituximab was associated with increased use of antimicrobial agents [median 5.9 DDD/100 patient days; interquartile range (IQR) 0.7-13] compared to use of fewer than 5 courses rituximab (median 0; IQR 0-2.2; P = 0.012). No difference was found in self-reported infections with prolonged use of rituximab. CONCLUSION: Until a full safety profile of rituximab is known, the prescriber's starting point can not be that prolonged rituximab use is safe with regard to development of problems in immunity. The patients need to be informed well in this matter