The pipeline of new antirheumatic drugs for RA promises to bring new therapeutic possibilities and challenges for the future. New agents will create opportunities to evaluate the benefits of novel induction regimens, mechanistic-based combination strategies, and tailor-made therapy for the individual patient. With potent induction regimens, drug-free holidays may be a realistic goal to mitigate the potential risks associated with the long-term use of immunosuppressive drugs. In the BeST study, a randomized trial comparing four different treatment strategies in early RA, 56% of 120 patients who started treatment with infliximab, 3 mg/kg, in combination with MTX were able to maintain a low disease activity score even after stopping infliximab . These encouraging results will provide impetus for further studies of drug withdrawal in the context of induction therapy for early RA. A shift in study designs must occur to accommodate the evolving standard of care for RA. The implementation of placebo-controlled trials will face ethical challenges because of the mounting evidence that persistent inflammation must be controlled as rapidly as possible to avoid progression of joint damage. Innovative study designs with appropriate statistical methodology are needed to determine the effects of contemporary and experimental treatment regimens on the progression of joint damage and functional disability past 12 to 24 months. More information is also needed to ascertain the effects of therapies on comorbidities (eg, cardiovascular disease) and mortality. Clinical trials are mostly designed now to test if an investigational therapy is better than standard of care, which is typically MTX alone. MTX monotherapy will not survive much longer as an acceptable standard of care with the perception that DMARDs must be added sequentially without delay to optimally suppress joint inflammation. As a result, upcoming study designs will feature more combination regimens as an active comparator and rely increasingly on noninferiority comparisons to usher new agents into clinical practice. Regardless, pioneering treatments to improve care of patients who have RA loom on the horizon.
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