Long-term Efficacy and Safety of Canakinumab in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA): Results From a Phase III Extension Study

Hermine Brunner¹, Nicolino Ruperto², Pierre Quartier³, Tamás Constantin², Ekaterina Alexeeva², Isabelle Koné-Paut⁴, Katherine Marzan⁵, Nico Wulffraat², Rayfel Schneider⁵, Shai Padeh⁶, Vyacheslav Chasnyk⁶, Carine Wouters⁶, Jasmin B. Kuemmerle-Deschner⁶, Tilmann Kallinich⁶, Bernard Lauwerys⁷, Elie Haddad⁵, Evgeny L Nasonov⁶, Maria Trachana⁶, Olga Vougiouka⁶, Karolynn Leon⁸, Eleni Vritzali⁹, Karine Lheritier¹⁰, Alberto Martini⁶ and Daniel Lovell⁵, ¹Rheumatology, PRCSG, Cincinnati, OH, ²PRINTO-Istituto Gaslini, Genoa, Italy, ³Necker-Enfants Malades Hospital, Paris, France, ⁴Hôpital Kremlin Bicetre, University of Paris SUD, Paris, France, ⁵PRCSG, Cincinnati, OH, ⁶PRINTO-Istituto Gaslini, Genova, Italy, ⁷Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium, ⁸Novartis Pharmaceuticals Corporation, East Hanover, NJ, ⁹Immunology and Dermatology Franchise, Novartis Pharma AG, Basel, Switzerland, ¹⁰Novartis Pharma AG, Basel, Switzerland

Meeting: 2017 Pediatric Rheumatology Symposium

Keywords: canakinumab and juvenile idiopathic arthritis (JIA), IL-1

Session Information

Date: Thursday, May 18, 2017

Title: Clinical and Therapeutic Poster Session

Session Type: Abstract Submissions

Session Time: 5:30PM-7:00PM

Background/Purpose: The management of SJIA with biological therapies is aimed to achieve and maintain clinical remission (CR), and accordingly taper corticosteroids (CS). Canakinumab (CAN) demonstrated high inactive disease (ID) rates in about 33% of patients (pts) on Day 15 and 30, respectively in previous studies.¹However, little is known about high level response rates in SJIA pts using CAN long-term. The objective of this study was to evaluate the long-term treatment response in terms of safety and efficacy in CAN treated pts with active SJIA.

Methods: This was an open-label, non-comparative study of CAN-naïve SJIA pts (age ≥2–<20 yrs) receiving subcutaneous CAN 4 mg/kg every 4 weeks. Efficacy was assessed every 3 months by the aACR (30/50/70/90/100) responses compared to baseline (BL), ID or CR (ID for >6 months) and changes in JADAS10-CRP scores over time. Safety was assessed by adverse events (AEs) and serious AEs (SAEs). The results are based on the observed data with imputations to carry the last observation forward.

Results: Of 123 pts with active SJIA, 70 (57%) had fever and 71 (57.7%) used corticosteroids at BL. Mean C-reactive protein (CRP) was 117.8 mg/L (normal: 0-10 mg/L), and, on average, pts had 9.9 active joints and 8.9 joints with limited motion. A rapid response was observed at Day 15: 59 (51%) and 27 (26%) pts had aACR ≥70 and aACR 100 responses, respectively. These responses were maintained at subsequent time points (Table). At Month 6, CR was achieved in 52 (42.3%) pts. Overall, 33 (26.8%) pts had CR for at least 12 months. At BL, the median JADAS10-CRP score was 22.3, with median changes from BL of −12.0 at Day 15 and −16.8 at last assessment, respectively. At the last assessment, 59 (48.4%) pts had ID (JADAS10 ≤1); 14 (11.5%) had low disease activity (JADAS10 >1 and ≤3.8), while 14 (11.5%) had moderate and 35 (28.7%) had high disease activity. Overall, 24 (33.8%) pts were steroid-free at last assessment. In total, 108 (87.8%) pts had at least 1 AE. Overall, exposure adjusted AE and SAE rate was 8.22 and 54.8 events/pt-years (pyr) respectively, with 183.56 pyr exposure and 40 (32.5%) pts had SAEs; most commonly reported SAEs were disease flares or worsening of SJIA in 13 (10.6%) pts, macrophage activation syndrome in 6 (4.9%) pts, and fever in 4 (3.3%) pts. No deaths occurred in this study.

Conclusion:

Canakinumab treatment was associated with rapid response and sustained therapeutic effect over the long-term in the naïve patients with active SJIA. The safety profile is consistent with other canakinumab studies.

Reference:

1. Ruperto et al. N Engl J Med. 2012; 367:2396-406.

Table: ACR responses achieved in the cohort by time point
Time point	CAN N=123
Time point	Minimum adapted ACR pediatric response	n (n/m%)	Patients with Inactive disease (n/m)%
Month 12	m Non-Responders aACR ≥30 aACR ≥50 aACR ≥70 aACR 100	85 4 (4.7) 81 (95.3) 77 (90.6) 73 (85.9) 49 (57.6)	(52/88) 59.1
Month 21	m Non-Responders aACR ≥30 aACR ≥50 aACR ≥70 aACR 100	65 3 (4.6) 62 (95.4) 58 (89.2) 54 (83.1) 39 (60.0)	(48/65) 73.8
Last Assessment	m Non-Responders aACR ≥30 aACR ≥50 aACR ≥70 aACR 100	121 28 (23.1) 93 (76.9) 89 (73.6) 81 (66.9) 62 (51.2)	62/122 (50.8)
n= number of patients who satisfy the criteria, m = number of patients with an assessment in the time period.

Disclosure: H. Brunner, 5,8; N. Ruperto, 2,8; P. Quartier, 2,5,8; T. Constantin, None; E. Alexeeva, 2,8; I. Koné-Paut, 2,5; K. Marzan, 2; N. Wulffraat, 2; R. Schneider, None; S. Padeh, None; V. Chasnyk, None; C. Wouters, 2; J. B. Kuemmerle-Deschner, 2,5; T. Kallinich, 2,8; B. Lauwerys, None; E. Haddad, None; E. L. Nasonov, None; M. Trachana, 2,5; O. Vougiouka, None; K. Leon, 3; E. Vritzali, 3; K. Lheritier, 1,3; A. Martini, 2,8; D. Lovell, 2,5,8.

To cite this abstract in AMA style:

Brunner H, Ruperto N, Quartier P, Constantin T, Alexeeva E, Koné-Paut I, Marzan K, Wulffraat N, Schneider R, Padeh S, Chasnyk V, Wouters C, Kuemmerle-Deschner JB, Kallinich T, Lauwerys B, Haddad E, Nasonov EL, Trachana M, Vougiouka O, Leon K, Vritzali E, Lheritier K, Martini A, Lovell D. Long-term Efficacy and Safety of Canakinumab in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA): Results From a Phase III Extension Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). https://acrabstracts.org/abstract/long-term-efficacy-and-safety-of-canakinumab-in-patients-with-active-systemic-juvenile-idiopathic-arthritis-sjia-results-from-a-phase-iii-extension-study-2/. Accessed .

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