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 1β (IL1β) 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.

The Inflammasomes in Kidney Disease

“…56 IL-1 antagonism immediately ameliorates the clinical symptoms of these crystal arthropathies. 57,58 In vitro studies and studies performed in mice also support a role of the NLRP3 inflammasome in translating the recognition of crystal or particle formats of silica, asbestos, cholesterol, ␤-amyloid, or hemozoin into IL-1␤ release and disease manifestations of silicosis, 29,59 asbestosis, 59 atherosclerosis, 60 Alzheimer's disease, 61 and malaria. 32,62 It would be interesting to know whether the same mechanism applies to kidney diseases that are associated with crystals or microparticles such as nephrolithiasis, renal amyloidosis, cholesterol embolism, urate nephropathy, cast nephropathy, or rhabdomyolysis.…”

The inflammasome as a target for pain therapy

“…117 Current strategies for targeting IL-1b have proved successful for alleviating the symptoms of gout in clinical studies, suggesting that targeting this and other components of the pathway may have an important role in gout treatment. [119][120][121][122][123][124] Interleukin-1 inhibitors currently in clinical trials include anakinra (IL-1 receptor antagonist), rilonacept (IL-1 Trap, a soluble decoy receptor), and canakinumab (anti-IL-1b monoclonal antibody). Anakinra has been shown to be efficacious for combating acute gout pain and inflammation, 119 whereas rilonacept has been revealed to be efficacious in reducing the risk of recurrent attacks.…”

Neutrophil: Lymphocyte Ratio and Mean Platelet Volume in Patients with Gout

“…In this context, three distinct complexes have been described in humans: NACHT leucine-rich repeat and pyrin domain-containing protein 1 (NALP1), NALP3, and Ice protease activating factor (IPAF).To date, NALP3 is the most extensively investigated inflammasome complex. Studies have shown that Toll-like receptor (TLR) and NALP3 inflammasome complex in concert result in IL-1ß and IL-18 production [23]. This becomes a focus of interest in studies on crystal-related arthropathies.…”