Background There is a medical need for effective alternate treatments for acute gouty arthritis (GA) patients (pts) with frequent GA attacks in whom NSAIDs and/or colchicine are contraindicated, not tolerated or ineffective.1 Canakinumab (CAN), a selective, fully human anti-interleukin-1β antibody, is the only biologic approved in EU for the treatment of pts with difficult-to-treat GA. Here, we present the results of pooled analyses from long-term extensions of two phase III studies with a cumulative duration of 18 months.
Objectives To evaluate the long term safety and efficacy (time to first attack) of CAN (subcutaneous) compared with triamcinolone acetonide (TA [intramuscular]) in GA pts with frequent attacks.
Methods GA pts who completed two multicentre randomised phase III core and respective randomised extensions (E1) of the same design, were rolled over into open-label extension studies (E2). All pts (irrespective of assigned treatment in core and E1) were treated with CAN 150 mg on demand upon new attack in E2. Safety was measured as exposure-adjusted incidence rate (IR) of adverse events (AEs). Time to first new attack was analysed using the Cox proportional hazard regression model.
Results Of 456 pts randomised in core studies, 335 entered the two E1 extensions. Of these 335 pts, 272 entered and 249 completed the E2 studies. Baseline characteristics of both treatment groups were similar. Mean number of doses per pt over cumulative duration of 18 months in pts randomized to CAN was 2.08. The overall IR of AEs in pts randomised to CAN was 330.8/100 pt-years (pyr). Incidence of AEs following CAN re-treatment was lower than the incidence prior to re-treatment (286.8/100 vs 385.0/100 pyr). A slightly lower IR of AEs was reported by pts who switched from TA to CAN (264.7/100 vs 229.9/100 pyr). Upper respiratory infections (7.8/100 pyr) were the most commonly reported infections with CAN while nasopharyngitis (6.6/100 pyr) was the most common infection with TA. Observed IR for serious AEs for CAN was 20.1/100 pyr and 16.4/100 pyr for TA. Over the cumulative duration of 18 months, 4 deaths, not suspected to be related to study drug, were observed: 1 intracranial haemorrhage (pt not re-treated with CAN); 1 pneumonia (pt re-treated with CAN), 1 sudden cardiovascular death and 1 pneumococcal sepsis (TA pts never receiving CAN). Over the cumulative duration of 18 months, the median time to first new attack was 242 days for CAN (inter-quartile range (IQR)=130–337, n=225) compared with 131 days for TA (IQR=49–376, n=229; p=0.0012, hazard ratio=0.68).
Conclusions The results of this pooled analyses support the long-term safety and efficacy of canakinumab treatment in pts with frequent GA attacks. The safety profile was consistent with the one observed in the core and E1 studies. Canakinumab significantly delayed the time to first new attack by more than 100 days, compared with TA, a long acting corticosteroid.
Schlesinger N. Drugs 2011;71 (11):1413–39.
Disclosure of Interest R. Alten: None declared, N. Schlesinger Grant/research support: Novartis, Consultant for: Novartis, SOBI; Advisory boards: Novartis, Takeda, Savient, Enzyme Rx, URL Pharma, SOBI, Speakers bureau: Novartis, Takeda, Savient, A. So Consultant for: Received honoraria for being member of the canakinumab advisory board, H. R. Schumacher Consultant for: Novartis, Regeneron, Abbvie, M. Bloch Grant/research support: payments to my institue for the conduct of clinical research, U. Machein Employee of: Novartis, D. Richard Shareholder of: Novartis, Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, T. Bardin Consultant for: Novartis, SOBI, Speakers bureau: Novartis