A CONTROLLED TRIAL OF CANAKINUMAB VS TRIAMCINOLONE ACETONIDE IN ACUTE GOUTY ARTHRITIS PATIENTS: RESULTS OF THE B-RELIEVED STUDY (RESPONSE IN ACUTE FLARE AND IN PREVENTION OF EPISODES OF RE-FLARE IN GOUT)

Background: Gouty arthritis is a painful, progressive, destructive, chronic inflammatory disease. Interleukin (IL)-1β is a key driver of the underlying inflammation resulting in painful flares and joint destruction, thereby making this cytokine an appropriate therapeutic target. Objectives: To evaluate the efficacy of canakinumab, a long-acting fully human monoclonal antibody selectively inhibiting IL-1β, vs. triamcinolone acetonide (TA) in treating acute flares and preventing recurrent flares in difficult-to-treat gouty arthritis patients. Methods: In this 12-week, multicenter, double-blind, double dummy, active-controlled trial, patients (≥18-≤85 yrs) with gouty arthritis, meeting preliminary ACR 1977 criteria with an acute flare of ≤5 days duration and who were unresponsive/intolerant or contraindicated to NSAIDs/colchicine were randomized to receive either canakinumab 150 mg sc or TA 40 mg im. The co-primary end-points were the effect on joint pain intensity on a 0-100 mm VAS scale (ANCOVA) 72 h post dose and time to first new gout flare (Cox proportional hazard regression model). Results: Of 230 patients enrolled (56 centers, in 16 countries majority of European centers), 228 (canakinumab: n=113, TA: n=115) received treatment. 214 (93%) patients completed the study and 16 (7%) discontinued (canakinumab: n=6; TA: n=10). Baseline characteristics were similar among treatment groups. At baseline, mean pain VAS scores were 73.3 and 74.8; 76.1% and 73.9% had severe/extreme pain on Likert scale; mean number of flares in previous year was 6.5 and 7; 50.4% and 54.8% were on urate lowering therapy, mean age was 50.6 and 52.6; 38.9% and 39.1% had tophi in canakinumab and TA patients, respectively. Canakinumab was superior to TA in reducing VAS pain score from 12 h to 7 days. At 72 h post dose (prim endpoint) the difference was -11.4 mm (95% CI: -18.2, -4.6, p=0.0005). A 33.3 mm decrease vs baseline VAS pain was observed at 24 h with canakinumab. The median time to 50% reduction in baseline pain (VAS) was significantly less with canakinumab (48 h) vs TA (72 h), p=0.0103. Canakinumab delayed the time to first new flare vs TA with a significant relative risk reduction of 55% (p≤0.001) within 3 months [HR: 0.45; 95% CI: 0.26, 0.76; p=0.0014]. The percentage of patients with at least 1 new gout flare was lower for canakinumab (18.6%) vs TA (34.8%) (OR: 0.46; 95% CI: 0.24, 0.68; p=0.0061). 55.8% of patients had AEs with canakinumab vs 38.3% with TA. SAEs (canakinumab: n=10, TA: n=5) were not considered to be related to study medication by the investigators. No sc injection site reactions were reported. Conclusions: This pivotal phase III study confirms the superiority of canakinumab over TA in relieving pain and reducing the risk of new flares in gouty arthritis patients unresponsive, intolerant or contraindicated to NSAIDs/colchicine. Thus, canakinumab could be a new treatment option for the underlying inflammation and pain associated with gouty arthritis in this difficult-to-treat population. Disclosure of Interest: A. So Consultant for: Bristol-Myers Squibb, MSD, Novartis, Pfizer, UCB, R. Alten Grant/Research support from: Novartis, Speakers Bureau: Novartis, Abbott, BMS, Roche, T. Bardin Consultant for: Novartis, Ipsen, Menarini, Savient, H. Schumacher Consultant for: Takeda, Novartis, Ardea, Xoma, Regeneron, Savient, Pfizer, M. Bloch Grant/Research support from: Novartis, A. Rolfe: None Declared, V. Murphy Shareholder of: Novartis, Employee of: Novartis, P. Sallstig Shareholder of: Novartis, Employee of: Novartis, D. Richard Shareholder of: Novartis, Employee of: Novartis, A. Gimona Shareholder of: Novartis, Employee of: Novartis, N. Schlesinger Grant/Research support from: Novartis, Consultant for: Novartis, Speakers Bureau: TakedaCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 104Session: Abstract Session: Bone and crystal diseases (Oral Presentations )