FRI0496 Efficacy and Safety of Canakinumab in Children with Systemic Juvenile Idiopathic Arthritis with and Without Fever

Background Canakinumab (CAN) leads to improvement for patients (pts) with systemic juvenile idiopathic arthritis (SJIA)1. However, little is known about potential differences in response to CAN treatment between pts with vs. without SJIA associated fever at the time of the first CAN administration. Objectives To evaluate the long-term efficacy and safety profile of CAN-naïve children with SJIA pts with and without SJIA associated fever. Methods Pts aged 2-20 yrs with SJIA with and without SJIA associated fever at enrollment received open-label CAN 4mg/kg s.c. every 4 wks. Every 3 months, response to CAN was measured by adapted JIA ACR response criteria (aACR/JIA); juvenile arthritis disease activity score [JADAS]; clinical inactive disease; clinical remission on medication [6 months continuous clinical inactive disease]. Safety was assessed monthly. Results Data on 122/267 pts, 53 (43%) with and 69 (57%) without SJIA associated fever, were available for analysis with a median 94 wk study duration. At Wk4, ∼75% of both subgroups had responded (≥aACR/JIA30), increasing to 90% at Wk12. At Wk2, ∼21% of both subgroups had inactive disease; 44% at Wk8; 60% at Wk20 and then 60-70% for the remainder of the trial. Clinical remission on medication was achieved in about 29% of pts in both subgroups with ∼22% maintaining it for ≥12 consecutive months. At baseline, the median JADAS score was 21.5 with 8 (7.5%) and 99 (92.5%) pts meeting the criteria for moderate (JADAS >3.8 and ≤10.5) and high disease activity (JADAS >10.5), respectively. At Day15, the median JADAS was 6.8 and 1.5 at the last assessment. In addition, at the last assessment, 53 (48%) pts were rated as inactive disease (JADAS ≤1); 10 (9%) with low active disease activity (JADAS >1 and ≤3.8); while 14 (13%) had moderate and 31 (28%) with high disease activity. A similar long-term safety profile to the pivotal program in children with fever at enrollment was observed in these CAN-naïve pts with or without fever. The most common type of adverse event (AE) reported was infection (0.56 infections/100 PT-days) typically involving the upper respiratory tract. Fifteen pts discontinued due to an AE and 40 had >1 SAE (mostly infections, macrophage activation syndrome [MAS], or flare-associated) and no deaths. Eight cases of MAS (0.013 events/100 pt-days) were reported. Conclusions Canakinumab provides similar efficacy (inactive disease, clinical remission) in SJIA pts with and without SJIA associated fever at treatment onset. The long-term safety profile was acceptable and similar to the pivotal program in SJIA children with fever at enrollment. References Ruperto et al. N Engl J Med. 2012; 367: 2396-406. Disclosure of Interest N. Ruperto Grant/research support from: Abbott, Bristol Myers and Squibb, Francesco Angelini S.P.A., Glaxo Smith & Kline, Janssen Biotech Inc Novartis,Pfizer Inc, Roche,Sanofi Aventis,Schwarz Biosciences GmbH: I declare that the GASLINI Hospital which is the public Hospital where I work as full time employee has received contributions to support the research activities of the network of PRINTO, Consultant for: Bristol Myers and Squibb, Centocor Research & Development,Glaxo Smith & Kline, Novartis, Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, I declare that 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 industries above mentioned, Speakers bureau: Abbott, Abbvie, Amgen, Astellas, Biogenidec, Boehringer, Bristol MyersSquibb, Celgene, CrescendoBio, EMD Serono, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Reumatic.com, Roche, Sanofi, Servier, Sinergie, Takeda, H. Brunner Consultant for: Novartis, Genentech, Pfizer, UCB, AstraZeneca, Biogen, Boehringer-Ingelheim, Regeneron, Speakers bureau: Novartis, Genentech, P. Quartier Grant/research support from: Abbvie, BMS, Chugai-Roche, Novartis, Pfizer, SOBI, Consultant for: Abbvie, Novartis, Servier, SOBI, Speakers bureau: Abbvie, BMS, Chugai-Roche, Medimmune, Novartis, Pfizer, SOBI, T. Constantin Consultant for: Pfizer, Abbvie, Roche, Novartis, Bristol-Myers Squibb, Speakers bureau: Pfizer, Abbvie, Roche, Novartis, Bristol-Myers Squibb, E. Alexeeva Grant/research support from: Roche, Abbott, Pfizer, Bristol-Myers Squibb, Centocor, Novartis, Speakers bureau: Roche, Merck Sharp &Dohme, Abbott, Bristol-Myers Squibb, Medac, Novartis, Pfizer, I. Kone-Paut Grant/research support from: To my institution: SOBI, Roche, Novartis, Consultant for: Novartis, SOBI, Pfizer, CHUGAI, Abbvie, K. Marzan Grant/research support from: Novartis and Abbvie, Employee of: University of Southern California, N. Wulffraat Grant/research support from: Novartis, Pfizer, Abbvie, SOBI, Consultant for: Novartis, Pfizer, SOBI, R. Schneider Consultant for: Novartis, Roche, S. Padeh: None declared, V. Chasnyk: None declared, C. Wouters Grant/research support from: Unrestricted grant support GSK, Novartis, Roche, J. Kummerle Deschner Grant/research support from: Novartis, Consultant for: Novartis, T. Kallinich Speakers bureau: Novartis, BMS and Pfizer, B. Lauwerys: None declared, E. Haddad: None declared, E. Nasonov: None declared, M. Trachana Grant/research support from: Abbvie, Novartis, Pfizer, Consultant for: Novartis, Pfizer, Roche, Speakers bureau: Novartis, Pfizer, Roche, O. Vougiouka Grant/research support from: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, K. Leon Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, A. Martini Grant/research support from: The Gaslini Hospital, which is the public Hospital where I work as a full time employee, has received contributions to support the research activities of the network of PRINTO from Bristol Myers and Squibb, Glaxo Smith & Kline, Janssen Biotech Inc, Novartis, Pfizer, Roche, Schwartz Bioscences GmbH, Speakers bureau: AbbVie, Boerhinger, Celgene, CrescendoBio, Janssen, Meddimune, Novartis, NovoNordisk, Pfizer, Sanofi Aventis, Vertex, Servier, D. Lovell Grant/research support from: National Institutes of Health, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene, Jannsen, Speakers bureau: Genentech, Roche, Novartis

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