Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials. Issue 12 (29th September 2018)

• Record Type: Journal Article
• Authors: Ruperto, Nicolino; Brunner, Hermine I; Quartier, Pierre; Constantin, Tamàs; Wulffraat, Nico M; Horneff, Gerd; Kasapcopur, Ozgur; Schneider, Rayfel; Anton, Jordi; Barash, Judith; Berner, Reinhard; Corona, Fabrizia; Cuttica, Ruben; Fouillet-desjonqueres, Marine; Fischbach, Michel; Foster, Helen E; Foell, Dirk; Radominski, Sebastião C; Ramanan, Athimalaipet V; Trauzeddel, Ralf; Unsal, Erbil; Levy, Jérémy; Vritzali, Eleni; Martini, Alberto; Lovell, Daniel J
• Is Part Of: Annals of the rheumatic diseases. Volume 77:Issue 12(2018)
• Page Start: 1710
• Page End: 1719
• Publication Date: 2018-09-29
• Subjects: canakinumab -- clinical trial -- interleukin-1β -- long-term extension -- systemic juvenile idiopathic arthritis.; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-213150
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: To evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA). Methods: Patients (2–19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR ). Efficacy analyses are reported as per the intent-to-treat population. Results: 144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CRACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed. Conclusion: Response to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab. Trial registration numbers: NCT00886769, NCT00889863, NCT00426218 and NCT00891046 .