B cell targeted therapies: safety considerations.

Reported data from recent clinical trials have contributed substantially to our growing understanding of the potential effectiveness and safety of B cell targeted therapy in the treatment of rheumatic diseases. Trials with rituximab, an anti-CD20 monoclonal antibody that depletes mature B cells, have amassed the most data of any B cell targeted therapy to date. A number of other B cell directed therapies are under investigation. Interestingly, although they may share a common target, the different agents have quite distinct mechanisms of action, and therefore their efficacy and safety profiles may differ. A common concern with all B cell directed therapies is the potential effect these agents may have on humoral immunity. The safety profile of rituximab in the oncology setting is well known, based on a database of well over 370,000 patients. Phase II trials of rituximab in rheumatoid arthritis (RA) have begun to examine safety issues specifically in the RA population, including issues surrounding longterm and repeated treatment safety profiles. Questions about the longterm safety of B cell therapy remain to be clarified: What will be the safety profile for repeated treatment courses? What will be the safety profile when B cell targeted therapies are used in sequence or in conjunction with other agents? Answers to these important questions are likely to come from careful observations by treating clinicians, data from registries, and longterm followup of patients enrolled in clinical trials.