Objective: Interleukin 1 (IL-1) plays a pivotal role in the pathogenesis of osteoarthritis (OA). In animal models of OA, IL-1 blockade by IL-1 receptor antagonist (IL-1Ra) can slow the progression of disease. We examined the safety of intraarticular (IA) injections of recombinant human IL-1Ra in patients with knee OA.
Methods: A prospective multicenter trial was conducted using the continual reassessment method. Six doses were considered, 0.05 mg up to 150 mg IL-1Ra, and the trial was double-blind regarding the dose administered. Patients with symptomatic knee OA and without synovial fluid effusion were included. Acute inflammatory reaction (the primary endpoint defining intolerance) was recorded if pain increase over 30 mm on 100 mm visual analog scale and synovial fluid effusion occurred within 72 h after the IA injection. As a secondary aim, efficacy was estimated (by total pain and Western Ontario and McMaster University OA functional index) until Month 3.
Results: One patient received 0.05 mg and 13 patients received 150 mg of IL-1Ra. No acute reaction occurred (one patient experienced postinjection joint swelling with no pain) and the 150 mg dose was considered the maximum tolerated dose (intolerance level 0%; confidence interval 0, 9.1%). A significant improvement was still observed until Month 3 in the 13 patients who received 150 mg IL-1Ra: pain improved by -20.4 +/- 23.3 mm (p = 0.008) and WOMAC global score by -19.5 +/- 20.1 (p = 0.005).
Conclusion: IA injection of IL-1Ra in patients with knee OA was well tolerated and did not induce any acute inflammatory reaction. The feasibility of such IA injections of IL-1Ra opens a promising therapeutic perspective for patients with OA.