Abstract 518: Placebo-Controlled Pilot Study of Rilonacept (IL-1 Trap), A Long Acting IL-1 Inhibitor, In Refractory Chronic Active Gouty Arthritis
Assil Saleh, M.D.
Authors:
Robert Terkeltaub, H. Ralph Schumacher, Jr., John Sundy, Frederick Murphy, Stephen Bookbinder, Stephanie Biedermann, Scott Mellis, Ke Yang, Allen Radin.
Background:
Interleukin-1 (IL-1) may be a principal mediator of pain and inflammation in gout and pseudogout, and its release may be triggered by monosodium urate and calcium pyrophosphate dihydrate crystals. Blocking IL-1, therefore, may be a viable strategy to control pain and inflammation in these disorders. Inhibition of IL-1 has been previously demonstrated by Rilonacept, a soluble receptor-Fc fusion protein. The safety and clinical effectiveness of this agent in treating chronic active gouty arthritis in humans was evaluated in this study.
Methods:
Ten patients with a history of at least six months of chronic gouty arthritis were studied in a non-randomized, single-blinded fashion. Two weekly subcutaneous injections of placebo were followed by six (one loading dose then five additional) weekly injections of rilonacept. Evaluations were conducted every two weeks then at six weeks after the last dose. Clinical responses were evaluated by subject pain visual analogue scale (VAS), subject and physician global VAS, joint count, and hs-CRP levels. The primary endpoint was safety. The secondary endpoints were VAS ratings, patient pain responder analysis, hs-CRP levels.
Results:
All 10 patients exhibited a treatment emergent adverse event at some point during follow-up, the most common being mild to moderately severe injection site reactions; however, no patient had a severe adverse reaction.
7/10 subjects had at least 50% improvement in subject pain VAS (p<0.0001) while 6/10 subjects had at least 75% improvement (p=0.0001). Neither level of improvement was observed during the placebo phase of the study
Median hs-CRP levels decreased 59% by week 8 of the study (p=0.004) but trended toward returning to baseline six weeks after discontinuing the rilonacept.
Conclusions:
Rilonacept is a well tolerated medication that can suppress gouty arthritis pain and reduce hs-CRP levels compared to placebo.
Editorial Comments:
This is a very small but useful study where rilonacept was shown to offer promise as an agent to treat gouty arthritis. It is associated with symptomatic improvement and no significant major adverse effects. The study is very preliminary, however. The sample size is exceedingly small (10 patients), and the lack of a double-blinded experimental design limits definitive conclusions on the safety and efficacy profile of this agent in the broad population of gout patients. Nonetheless, it is a well constructed first step toward what will possibly be the incorporation of another effective strategy in gout therapy.
