Background/Purpose: Gouty arthritis (GA) is a painful, progressive, destructive, chronic inflammatory disease. Targeting the inflammatory pathway through IL-1β inhibition with canakinumab, a fully human anti-IL-1β monoclonal antibody, is a novel therapeutic approach that may provide significant long-term benefits in this patient group. In 2 pivotal 12-week controlled trials (β-RELIEVED and β-RELIEVED-II), canakinumab showed superiority to triamcinolone acetonide (TA) in relieving pain, inflammation and delaying risk of new flares in GA patients with limited treatment options. We report the results of two extension studies that assessed long-term efficacy, safety and tolerability.
Methods: In two 12-week, multicenter, active-controlled trials, acute GA patients (meeting preliminary ACR-1977 criteria for acute GA and unresponsive, intolerant or contraindicated to NSAIDs and/or colchicine) were randomized to receive canakinumab 150mg sc or TA 40mg im, followed by two 12-week extension studies. Patients received canakinumab 150mg sc or TA 40mg im for the baseline flare and only “on demand” for any new flare. Time to first new flare, mean number of flares, physician's and patient's global assessment of treatment response (Likert scale) and safety over 24 weeks are assessed.
Results: 416 patients completed the core studies (β-RELIEVED: 214; β-RELIEVED-II: 202). 335 patients (β-RELIEVED: 175; β-RELIEVED-II: 160) entered the extension studies and 317 completed (β-RELIEVED E1: 167; β-RELIEVED-II E1: 150). Over 24-weeks following randomization, canakinumab delayed the time to first new flare vs TA with a statistically significant relative risk reduction of 52% in β-RELIEVED E1 and 60% in β-RELIEVED-II E1 (Table). The mean number of flares per patient was significantly reduced with canakinumab. At Week 24, a higher percentage of patients taking canakinumab achieved a better assessment of treatment response from physicians and patients. Incidence of AEs for canakinumab and TA in both studies was: β-RELIEVED E1: 62.8% vs 48.7%; β-RELIEVED-II E1: 69.6% vs 57%, respectively. Most AEs were mild to moderate in severity. No discontinuations due to AEs were observed in β-RELIEVED E1. 2 (1.8%) patients treated with canakinumab in β-RELIEVED-II E1 discontinued. SAEs [β-RELIEVED E1: canakinumab, n =11; TA n=6; β-RELIEVED-II E1: canakinumab n=7; TA n=2] were not considered to be related to study medication by the investigators. Most patients had no injection site reactions [β-RELIEVED E1: canakinumab, n=0; TA n=0; β-RELIEVED-II E1: canakinumab n=2; TA n=1].
Conclusions: In frequently flaring patients with limited treatment options, canakinumab demonstrated superior 24 week efficacy against TA with comparable safety and tolerability to 12-week data.
Disclosure: J. P. Brown, Abbott, Amgen Inc., Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, sanofi-aventis, Servier and Warner Chilcott, 2, Amgen Inc., Eli Lilly, Novartis, Merck, sanofi-aventis, Warner Chilcott, 5, Amgen Inc., Eli Lilly, Novartis, 8 ; A. So, MSD, Novartis, UCB, Pfizer Inc, 5 ; A. Dikranian, URL Pharma, 8 ; R. Alten, Novartis Pharmaceutical Corporation, 2 ; T. Bardin, Novartis, Ipsen, Menarini, Savient, 5 ; H. R. Schumacher, Takeda, Novartis, Ardea, Xoma, Regeneron, Savient, Pfizer, 5 ; A. Gimona, Novartis Pharma AG, 1, Novartis Pharma AG, 3 ; G. Krammer, Novartis Pharma AG, 1, Novartis Pharma AG, 3 ; A. Karpov, Novartis Pharma AG, 1, Novartis Pharma AG, 3 ; N. Schlesinger, Novartis Pharmaceutical Corporation, 2, Novartis Pharmaceutical Corporation, 5, Takeda, 8 .