Open Access Research article

Rilonacept in the treatment of acute gouty arthritis: a randomized, controlled clinical trial using indomethacin as the active comparator

Robert A Terkeltaub1*, H Ralph Schumacher2, John D Carter3, Herbert SB Baraf4, Robert R Evans5, Jian Wang6, Shirletta King-Davis7 and Steven P Weinstein5

Author affiliations

1 Division of Rheumatology, Allergy and Immunology, VA Healthcare System San Diego and University of California at San Diego School of Medicine, 3350 La Jolla Village Drive, San Diego, CA 92161, USA

2 VA Medical Center and University of Pennsylvania, 151K, University & Woodland Avenues, Philadelphia, PA 19104, USA

3 Division of Rheumatology, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA

4 The Center for Rheumatology and Bone Research, 2730 University Boulevard West, Suite 310, Wheaton, MD 20902, USA

5 Clinical Sciences, Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA

6 BioStatistics, Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA

7 Clinical Trial Management, Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA

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Citation and License

Arthritis Research & Therapy 2013, 15:R25  doi:10.1186/ar4159

Published: 1 February 2013

Abstract

Introduction

In phase-3 clinical trials, the interleukin (IL-1) blocker, rilonacept (IL-1 Trap), demonstrated efficacy for gout flare prevention during initiation of urate-lowering therapy. This trial evaluated rilonacept added to a standard-of-care, indomethacin, for treatment of acute gout flares.

Methods

Adults, aged 18-70 years, with gout presenting within 48 hours of flare onset and having at least moderate pain as well as swelling and tenderness in the index joint were randomized to subcutaneous (SC) rilonacept 320 mg at baseline plus oral indomethacin 50 mg TID for 3 days followed by 25 mg TID for up to 9 days (n = 74); SC placebo at baseline plus oral indomethacin as above (n = 76); or SC rilonacept 320 mg at baseline plus oral placebo (n = 75). The primary efficacy endpoint was change in pain in the index joint (patient-reported using a Likert scale (0 = none; 4 = extreme)) from baseline to the average of values at 24, 48 and 72 hours (composite time point) for rilonacept plus indomethacin versus indomethacin alone. Comparison of rilonacept monotherapy with indomethacin monotherapy was dependent on demonstration of significance for the primary endpoint. Safety evaluation included clinical laboratory and adverse event (AE) assessments.

Results

Patient characteristics were comparable among the groups; the population was predominantly male (94.1%), white (75.7%), with mean ± SD age of 50.3 ± 10.6 years. All treatment groups reported within-group pain reductions from baseline (P < 0.0001). Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55 ± 0.92) relative to indomethacin alone (-1.40 ± 0.96), the difference was not statistically significant (P = 0.33), so formal comparison between monotherapy groups was not performed. Pain reduction over the 72-hour period with rilonacept alone (-0.69 ± 0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours. Treatment with rilonacept was well-tolerated with no reported serious AEs related to rilonacept. Across all groups, the most frequent AEs were headache and dizziness.

Conclusions

Although generally well-tolerated, rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare.

Trial registration

ClinicalTrials.gov registration number NCT00855920.