Talk: Canakinumab (ACZ885) Vs. Triamcinolone Acetonide for Treatment of Acute Flares and Prevention of Recurrent Flares in Gouty Arthritis Patients Refractory to or Contraindicated to NSAIDs and/or Colchicine (2009 ACR/ARHP Annual Scientific Meeting)

Tuesday, October 20, 2009: 5:15 PM

204 B (Pennsylvania Convention Center)

Alexander So¹, Marc De Meulemeester², Talha Shamim³, Andrey Pikhlak⁴, A. Eftal Yücel⁵, Udayasankar Arulmani⁶, Dominik Richard⁶, Valda Murphy⁶, Peter Sallstig⁶ and Naomi Schlesinger⁷, ¹CHU Vaudois, University of Lausanne, Lausanne, Switzerland, ²Gozee, Belgium, ³Heartland Clinical Research, Omaha, NE, ⁴Moscow State University of Medicine and Dentistry, Moscow, Russia, ⁵Baskent University, Ankara, Turkey, ⁶Novartis Pharma AG, Basel, Switzerland, ⁷UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ

Presentation Number: LB4

Purpose Current treatments for arthritis flares in gout (gouty arthritis) are not effective in all patients and may be contraindicated in many due to underlying comorbidities. Urate crystals activate the NALP 3 inflammasome which stimulate production of IL-1β, driving inflammatory processes. Targeted IL-1β blockade may be an alternative treatment for gouty arthritis. Canakinumab (ACZ885) is a fully human monoclonal anti- IL-1β antibody with a long half-life (28 days).

Method This was an 8-weeks, dose-ranging, multicenter, blinded, double-dummy, active-controlled trial of patients ≥18 to ≤80 y with an acute gouty arthritis flare, refractory to or contraindicated to NSAIDs and/or colchicine. Patients were randomized to 1 subcutanous (sc) dose of canakinumab (10, 25, 50, 90, or 150 mg) or 1 intra muscular (im) dose of triamcinolone acetonide (TA) [40 mg]. The primary variable was assessed 72 h post-dose, measured on a 0-100 mm VAS pain scale. Secondary variables included pain intensity 24 and 48 h post dose, time to 50% reduction in pain intensity, and time to recurrence of gout flares up to 8 weeks post dose.

Results 200 patients were enrolled (canakinumab n=143, TA n=57) and 191 completed the study. A statistically significant dose response was observed at 72 h. The 150 mg dose reached superior pain relief compared to TA starting from 24h: estimated mean difference in pain intensity on 0-100 mm VAS was -11.5 at 24 h, -18.2 at 48 h, and -19.2 at 72 h (all p<0.05). Canakinumab 150 mg provided a rapid onset of pain relief: median time to 50% reduction in pain was reached at 1 day with canakinumab 150 mg vs 2 days for the TA group (p=0.0006). The probability of recurrent gout flares was 3.7% with canakinumab 150 mg vs. 45.4% with TA 8 weeks post treatment, a relative risk reduction of 94% (p=0.006). Serious AEs occurred in 2 patients receiving canakinumab (appendicitis and carotid artery stenosis) and 1 receiving TA (cerebrovascular disorder). Investigator’s reported these events as not study drug related. There were no discontinuations due to AEs.

Conclusion Canakinumab 150 mg provided faster onset and superior pain relief compared to TA for acute flares in gouty arthritis patients refractory to or contraindicated to standard treatments. The 150 mg dose of canakinumab prevented recurrence of gout flares with a relative risk reduction compared to TA of 94% at 8 weeks post-dose, and was well tolerated.

Keywords: gout, inflammation and interleukins (IL)

Disclosure: A. So, Novartis Pharma AG; Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UBC, Wyeth, 5 ; M. De Meulemeester, None; T. Shamim, None; A. Pikhlak, Novartis Pharma AG, 2 ; A. E. Yücel, None; U. Arulmani, Novartis Pharma AG, 3 ; D. Richard, Novartis Pharma AG, 3 ; V. Murphy, Novartis Pharma AG, 3 ; P. Sallstig, Novartis Pharma AG, 3 ; N. Schlesinger, Novartis Pharmaceutical Corporation, 2 .

LB4 - Canakinumab (ACZ885) Vs. Triamcinolone Acetonide for Treatment of Acute Flares and Prevention of Recurrent Flares in Gouty Arthritis Patients Refractory to or Contraindicated to NSAIDs and/or Colchicine