It is gratifying to see Dr. Abeles' interest in our group's phase II study of the effect of rilonacept against gout flares in patients in whom urate-lowering therapy is being initiated. The trial, as he suggests, was designed to show initial and clear evidence of efficacy in flare prevention and could obviously not determine how this drug might ultimately be used clinically.
Regarding active comparators, for investigating a new drug in early, midsized studies, use of a placebo comparator, if feasible, is a better way of estimating treatment effect size, especially if the effect of an active comparator is based on a paucity of data. In this regard, it is important to note that colchicine, which has been embraced as the standard of care (as mentioned by Dr. Abeles), was compared with placebo for gout flare prophylaxis in a trial that was half the size of our phase II study of rilonacept (Borstad GC, Bryant LR, Abel MP, Scroggie DA, Harris MD, Alloway JA. Colchicine for prophylaxis of acute flares when initiating allopurinal for chronic gouty arthritis. J Rheumatol 2004;31:2429–32). Although we had not proposed at any point to study rilonacept against any active comparator, doing that could be of interest in the future.
Safety is rarely established in a phase II study, but it is notable that no untoward safety signals were evident in our trial. Phase III studies are now being reviewed, and these should be informative. The intended use of this promising agent is for a limited period of time after initiation of urate-lowering therapy, to abolish the transient excess flare risk. Urate-lowering therapies, not prophylactic agents, remain the agents that address the primary cause of gout. There is no intimation that rilonacept is being proposed for long-term use as in the 3-year study of anakinra for rheumatoid arthritis that Dr. Abeles has cited (Fleischmann RM, Tesser J, Schiff MH, Schechtman J, Burmester GR, Bennett R, et al. Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Ann Rheum Dis 2006;65:1006–12) or that rilonacept will replace nonsteroidal antiinflammatory drugs or colchicine when they are appropriate, effective, and tolerated.