The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, non-randomised, single-blind pilot study

Abstract

Background: Recent studies suggest that blockade of the NLRP3 (cryopyrin) inflammasome interleukin 1beta (IL1beta) pathway may offer a new treatment strategy for gout.

Objective: To explore the potential utility of rilonacept (IL1 Trap) in patients with chronic active gouty arthritis in a proof-of-concept study.

Methods: This 14-week, multicentre, non-randomised, single-blind, monosequence crossover study of 10 patients with chronic active gouty arthritis included a placebo run-in (2 weeks), active rilonacept treatment (6 weeks) and a 6-week post-treatment follow-up.

Results: Rilonacept was generally well tolerated. No deaths and no serious adverse events occurred during the study. One patient withdrew owing to an injection-site reaction. Patients' self-reported median pain visual analogue scale scores significantly decreased from week 2 (after the placebo run-in) to week 4 (2 weeks of rilonacept) (5.0 to 2.8; p<0.049), with sustained improvement at week 8 (1.3; p<0.049); 5 of 10 patients reported at least a 75% improvement. Median symptom-adjusted and severity-adjusted joint scores were significantly decreased. High-sensitivity C-reactive protein levels fell significantly.

Conclusions: This proof-of-concept study demonstrated that rilonacept is generally well tolerated and may offer therapeutic benefit in reducing pain in patients with chronic refractory gouty arthritis, supporting the need for larger, randomised, controlled studies of IL1 antagonism such as with rilonacept for this clinical indication.

Figure 1

Study design schematic.

Figure 2

(A) Patient pain visual analogue score (VAS) (median). *p Value from signed-rank test. Pain scores indicate the level of pain experienced by the patient over the preceding 24 h and reported at a study visit. On a 10-point scale, “0” represented “no pain,” and “10” represented “severe pain.” (last observation carried forward (LOCF); n = 10). The LOCF was used to assign any missing values. (B) Patient’s global assessment score (median). On a 10-point scale, “0” represented normal/none and “10” represented severe; LOCF; n = 10. ^†Week 2 vs day 0; ^‡week 8 vs week 2 (see online supplementary text files 1 and 2). (C) Symptom and severity-adjusted joint scores (median). Symptom-severity adjusted joint scores were derived by weighting the joint count by severity (1, mild; 2, moderate; 3, severe) for each symptom (swelling, tenderness and erythema) for each joint for a possible maximum score of 9 per joint. ^†Week 2 vs day 0; ^‡week 8 vs week 2. (D) High-sensitivity C-reactive protein (hsCRP) levels (median). Normal limit <0.287 mg/dl (defined by central laboratory). ^†Week 2 vs day 0; ^‡week 8 vs week 2.

Figure 3

(A) Pain responder analysis. Last observation carried forward (LOCF) (n = 10). (B) Pain responder analysis. LOCF (n = 10). *Week 2 to day 0; **week 4 vs week 2; ^†week 6 vs week 2; ^‡week 8 vs week 2.