Background Canakinumab (CAN), a selective, fully-human anti-IL-1β monoclonal antibody is approved for SJIA in over 30 countries. Efficacy and safety of CAN over 12 weeks have been demonstrated in 2 phase III trials.1 In these trials, >60% of the pts received a previous biologic and were switched to CAN due to lack of efficacy or for safety reasons, and may be more refractory to another biologic therapy.
Objectives To present a post-hoc evaluation of CAN efficacy in biologic-naïve (BN) pts and those previously exposed to biologics (BE) during the first 12-weeks.
Methods Pooled data from CAN naïve pts, enrolled in two phase III trials1 and an extension phase (up to interim data lock 10 August 2012) were considered. Pts (2–19 yrs) with active SJIA were enrolled and received CAN 4 mg/kg or placebo sc every 4 weeks for 12 weeks. CAN naïve pts who entered the trials and received at least one dose of CAN were included in this analysis (N=178 CAN naïve pts). Descriptive efficacy analyses of adapted ACR-JIA responses at Week 12 are provided for the BN and BE pts groups.
Results At baseline, there were 66 (37%) BN pts whereas anakinra (ANA), tocilizumab (TCZ), etanercept (ETN) and adalimumab (ADA), were the biologics received by 78 (44%), 10 (6%), 58 (33%) and 9 (5%) pts, respectively. The main reasons for discontinuation of biologics in BE group (n=112) was lack of efficacy (ANA, n=32; TCZ, n=7; ETN, n=56; ADA, n=9) or safety/tolerability (ANA, n=20; TCZ, n=4, ETN, n=0). At Week 12, the BN and BE groups were similar in aACR-JIA 30 and 50 response rates. Numerically higher aACR-JIA 70 and 90 response rates were achieved in BN vs. BE pts (Table). aACR-JIA 70 and 90 response rates were similar in pts previously exposed to ANA vs those not exposed to ANA at 12 weeks (aACR-JIA70: 58% vs.63% and aACR-JIA 90:47% vs 50%). Compared to pts who discontinued ANA due to lack of efficacy, there was a trend towards higher aACR-JIA 70 and 90 response rates at Week 12 in pts who stopped ANA for other reasons (aACR-JIA70: 34% vs.74%; aACR-JIA90: 25% vs. 63%). A higher aACR-JIA 30, 50, 70 and 90 response rates were observed in TCZ naïve pts vs. those pts exposed to TCZ (n=10) [aACR-JIA30: 71% vs.50%; aACR-JIA50: 70% vs. 50%; aACR-JIA70: 61% vs.50%; aACR-JIA90: 49% vs. 40%]. Higher aACR-JIA 70 and 90 responses were observed for ETN naïve pts vs. those exposed to ETN [aACR-JIA70: 67% vs. 48%; aACR-JIA90: 58% vs. 31%]; while ADA- naïve pts had similar responses to CAN as ADA-exposed pt (aACR-JIA 70: 61% vs 56%) and they had higher aACR-JIA 90 response (aACR-JIA90: 50% vs. 22%).
Conclusions In general, BE pts achieved aACR-JIA 50,70 and 90 responses to CAN quickly in the first 2 weeks, and maintained their response up to Week 12; albeit at a numerically lower level than BN pts. These data support the consistent efficacy of CAN across different subgroups of pts.
Ruperto N, et al. N Engl J Med 2012;367(25).
Disclosure of Interest P. Quartier Grant/research support: Abbvie, BMS, Chugai-Roche, Novartis, Pfizer and SOBI, Consultant for: Abbvie, Chugai-Roche, Novartis, Pfizer, Servier and SOBI, Speakers bureau: Chugai-Roche, MEDIMMUNE, Novartis, Pfizer, A. Grom Consultant for: Novartis, Roche, NovImmune, N. Ruperto Grant/research support: To Gaslini Hospital: Abbott, Astrazeneca, BMS, Centocor Research & Development, Eli Lilly and Company, “Francesco Angelini”, Glaxo Smith & Kline, Italfarmaco, Novartis, Pfizer Inc., Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc., Speakers bureau: Astrazeneca, Bristol Myers and Squibb, Janssen Biologics B.V., Roche, Wyeth/Pfizer, H. Brunner Consultant for: Novarits, Roche, Astrazeneca, Celgene, Pfizer, Janssen, UCB, GSK, BMS, Speakers bureau: Novartis, K. Schikler Grant/research support: Pfizer, Novartis, Abbvie, Roche, Genentech, Speakers bureau: Abbvie, Novartis, M. Erguven: None declared, L. Goffin Consultant for: Novartis, Pfizer, M. Hofer Grant/research support: Novartis, Pfizer, Abbvie, T. Kallinich Grant/research support: Novartis, Speakers bureau: Roche, Novartis, ALK, K. Marzan Grant/research support: Novartis, C. Gaillez Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, A. Martini Grant/research support: The Gaslini Hospital, which is the public Hospital where I work as full time employee, has received contributions to support the PRINTO research activities from the following companies: Bristol Myers and Squibb, Centocor Research & Development, Glaxo Smith & Kline,Novartis,Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH., Speakers bureau: Abbott, Bristol MyersSquibb, Astellas, Behringer, Italfarmaco, MedImmune, Novartis, NovoNordisk, Pfizer,Sanofi, Roche, Servier, D. Lovell Grant/research support: National Institutes of Health- NIAMS, Consultant for: Astra-Zeneca, Centocor, Amgen, Bristol Meyers Squibb, Abbott, Pfizer, Regeneron, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Speakers bureau: Novartis, Roche
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