AB1182 Efficacy and safety of canakinumab, fully human anti-interleukin-1beta antibody, in systemic juvenile idiopathic arthritis
Authors: N. Ruperto, H. Brunner, P. Quartier, T. Constantin, N. Wulffraat, G. Horneff, R. Brik, L. McCann, O. Kasapcopur, L. Rutkowska-Sak, R. Schneider, Y. Berkun, I. Calvo, M. Erguven, L. Goffin, M. Hofer, T. Kallinich, S. Knupp, Y. Uziel, S. Viola, K. Nistala, C. Wouters, R. Cimaz, M. Ferrandiz, B. Flato, M. Luz Gamir, I. Kone-Paut, A. Grom, B. Magnusson, S. Ozen, F. Sztajnbok, K. Lheritier, D. Kim, K. Abrams, A. Martini, D. Lovell
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic juvenile idiopathic arthritis (SJIA) is an IL1β-mediated autoinflammatory disease, characterized by spiking intermittent fever, rash, and arthritis. Canakinumab (CAN), a selective, fully human, anti-IL1β monoclonal antibody has shown promising efficacy and safety data in SJIA patients (pts). <h3>Objectives</h3> To demonstrate CAN allows tapering of corticosteroids (CS) and to evaluate time to flare in CAN vs placebo (PCB) pts with SJIA and active systemic features. <h3>Methods</h3> This Phase 3 trial had two parts. In Part 1 (P1), all patients (2-20 yrs) received open label CAN to identify responders and to taper CS. In Part 2 (P2), pts who successfully tapered their CS were randomized to receive CAN or PCB. In P1, pts received CAN (4mg/kg; max 300 mg) sc injection every 4 wks. Primary objectives were to determine if ≥25% of pts on CS at study entry could successfully taper the CS dose (P1); if time to flare was longer for CAN vs PCB (P2), and safety. <h3>Results</h3> 177 pts (128 on CS; 49 steroid-free) entered P1, of which 100 pts (CAN, n=50; PCB, n=50) entered P2; most of the remaining 77 pts were eligible (&gt;ACR30 at Day 15) to directly enter an open-label extension study following P1. In P1, 92 pts attempted CS tapering and 57 (62%) were successful, representing 44.5% (57/128; p&lt;0.0001) of pts on CS at study entry. 46% (42/92) of pts who attempted CS reduction and 33% (42/128) of pts on CS at study entry discontinued the CS. In P2, the median time to flare was 236 days (95%CI: 141-449 days) for PCB vs not determinable for CAN as &lt;50% had flared, corresponding to a 63% relative risk reduction in flare for CAN vs PCB (HR 0.37; 95%CI: 0.17-0.78; p=0.0043). In P1, 78% (138/177) of pts had AEs, of which infections of the upper respiratory tract were the most common. Five pts discontinued due to an AE and 14 pts had ≥1 SAE; mostly infections, MAS, or flare-associated events. 1 pt on CAN had died with MAS. In P2, a direct comparison of safety between the 2 groups was difficult as all pts were exposed to CAN in P1. 80% of pts on CAN and 70% on PCB had ≥1 AE, with infections of the upper respiratory tract being the most common in both groups. 4 pts on PCB discontinued due to an AE, and SAEs were reported in 6 pts in each group; mostly due to an infection, MAS, or flare-associated event. 1 fatal MAS case occurred in 1 pt after 6 months of PCB. <h3>Conclusions</h3> For SJIA patients with active features, canakinumab sc injection every 4 weeks allowed successful steroid tapering, with one third being able to discontinue their CS. Canakinumab significantly decreased the risk of SJIA flare, while demonstrating an acceptable safety and tolerability profile. <h3>Disclosure of Interest</h3> N. Ruperto Grant/Research support from: Abbott, Astrazeneca, Bristol Myers and Squibb, Centocor Research &amp; Development, Eli Lilly and Company, "Francesco Angelini" s.p.a, Glaxo Smith &amp; Kline, Italfarmaco, Merck Serono, Novartis, Pfizer Inc., Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc., Speakers Bureau: Astrazeneca, Novartis, Bristol Myers and Squibb, Roche, Janssen Bilogics B.V., H. Brunner Consultant for: Novartis, UCB, Genentech, Jansen, GSK and Medimmune, Paid Instructor for: Participant in Scientific Advisory Committee for Canakinumab program in SJIA, P. Quartier Speakers Bureau: Novartis, T. Constantin: None Declared, N. Wulffraat: None Declared, G. Horneff Grant/Research support from: Abbott, Pfizer, Consultant for: Abbott, Pfizer, Novartis, Roche, R. Brik: None Declared, L. McCann: None Declared, O. Kasapcopur: None Declared, L. Rutkowska-Sak: None Declared, R. Schneider Consultant for: Hoffman-La-Roche, Speakers Bureau: Hoffman-La-Roche, Y. Berkun: None Declared, I. Calvo: None Declared, M. Erguven Grant/Research support from: Novartis, L. Goffin: None Declared, M. Hofer Consultant for: Novartis, T. Kallinich Speakers Bureau: Novartis, S. Knupp: None Declared, Y. Uziel Consultant for: Novartis, S. Viola: None Declared, K. Nistala Grant/Research support from: Arthritis Research UK Career Progression Fellow, C. Wouters: None Declared, R. Cimaz: None Declared, M. Ferrandiz Grant/Research support from: Novartis, B. Flato: None Declared, M. Luz Gamir: None Declared, I. Kone-Paut: None Declared, A. Grom Consultant for: Novartis, J&amp;J, B. Magnusson Grant/Research support from: Swedish Association of local Authorities and Regions, Consultant for: Roche AB, S. Ozen Consultant for: Novartis, F. Sztajnbok: None Declared, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, D. Kim Shareholder of: Novartis, Employee of: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, A. Martini Grant/Research support from: Abbott, Astrazeneca, Bristol Myers and Squibb, Centocor Research &amp; Development, Eli Lilly and Company, "Francesco Angelini" s.p.a, Glaxo Smith &amp; Kline, Italfarmaco, Merck Serono, Novartis, Pfizer Inc., Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc., Speakers Bureau: Astrazeneca, Novartis, Bristol Myers and Squibb, Glaxo Smith &amp; Kline, D. Lovell Consultant for: Abbott Laboratories, Centocor Inc, Amgen, Astra Zeneca Pharmaceutical, Bristol-Myers Squibb, Hoffmann-La Roche, Inc., Novartis Pharmaceutical Corporation, Pfizer Inc, Regeneron, UBC, Wyeth Pharmaceuticals, Xoma Corporation, Speakers Bureau: Wyeth Pharmaceuticals