Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial.
OBJECTIVE
To evaluate the interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy.


METHODS
In this double-blind study, adult patients with hyperuricemia and gout were randomized to receive rilonacept administered subcutaneously once per week (loading dose 320 mg followed by 160 mg weekly) or placebo, and started on allopurinol (300 mg/day, titrated to serum urate <6 mg/dl). At study visits, physical and laboratory assessments were performed and information on any adverse events was ascertained.


RESULTS
Baseline characteristics were similar between the rilonacept and placebo groups (n = 41 and n = 42, respectively). The mean number of gout flares per patient through week 12 (primary efficacy end point) was markedly lower in the rilonacept group than in the placebo group (0.15 [6 flares] versus 0.79 [33 flares]; P = 0.0011). Fewer flares were observed with rilonacept as early as 4 weeks after initiation of treatment (P = 0.007). The proportion of patients experiencing a flare during the 12 weeks was lower in the rilonacept group than in the placebo group (14.6% versus 45.2%; P = 0.0037). No rebound in the flare rate was observed for 6 weeks after discontinuation of rilonacept or placebo at week 16. Adverse events were similar between groups, and no deaths or serious infectious adverse events were reported; the most common adverse events were infections (14.6% and 26.2% of rilonacept- and placebo-treated patients, respectively) and musculoskeletal disorders (14.6% and 21.4%, respectively). A higher percentage of rilonacept-treated patients (98%) compared with placebo-treated patients (79%) completed the primary 12-week evaluation period (P = 0.015).


CONCLUSIONS
The current findings indicate that rilonacept significantly reduces the frequency of gout flares during the initial period of treatment with urate-lowering therapy, with a favorable safety profile.
University of Pennsylvania and Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA. schumacr@mail.med.upenn.edu
H Ralph
HR
Schumacher
John S
JS
Sundy
Robert
R
Terkeltaub
Howard R
HR
Knapp
Scott J
SJ
Mellis
Neil
N
Stahl
George D
GD
Yancopoulos
Yuhwen
Y
Soo
Shirletta
S
King-Davis
Steven P
SP
Weinstein
Allen R
AR
Radin
D000493:Allopurinol / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006073:Gout / Q000188:drug therapy* / Q000473:pathology; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy* / Q000473:pathology; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D006074:Gout Suppressants; D011993:Recombinant Fusion Proteins; D000493:Allopurinol; C531377:rilonacept