Long-Term Efficacy and Safety of Canakinumab in Patients with Active Systemic Juvenile Idiopathic Arthritis (SJIA): Results from a PHASE III Extension Study

Hermine I. Brunner¹, Nicolino Ruperto², Pierre Quartier³, Tamás Constantin⁴, Ekaterina Alexeeva⁵, Isabelle Koné-Paut⁶, Katherine Marzan⁷, Nico Wulffraat⁵, Rayfel Schneider⁷, Shai Padeh⁵, Vyacheslav Chasnyk⁸, Carine Wouters⁵, Jasmin B. Kuemmerle-Deschner⁵, Tilmann Kallinich⁵, Bernard Lauwerys⁹, Elie Haddad⁷, Evgeny L Nasonov⁵, Maria Trachana⁵, Olga Vougiouka⁵, Karolynn Leon¹⁰, Eleni Vritzali¹¹, Karine Lheritier¹², Alberto Martini⁵ and Daniel J Lovell¹³, ¹Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ²Pediatria II, Reumatologia, Istituto Giannina Gaslini, Genoa, Italy, ³Hôpital Necker-Enfants Malades, Paris, France, ⁴Paediatric Rheumatology International Trials Organization (PRINTO), Genova, Italy, ⁵PRINTO-Istituto Gaslini, Genova, Italy, ⁶Pediatric Rheumatology, Department of Paediatric Rheumatology, AP-HP Bicêtre Hospital, Le Kremlin Bicêtre, France, ⁷PRCSG, Cincinnati, OH, ⁸PRINTO-Istituto Gaslini, Genoa, Italy, ⁹Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium, ¹⁰Novartis Pharmaceuticals Corporation, East Hanover, NJ, ¹¹Immunology and Dermatology Franchise, Novartis Pharma AG, Basel, Switzerland, ¹²Novartis Pharma AG, Basel, Switzerland, ¹³Rheumatology, PRCSG Cincinnati Children's Hospital Medical Center, Cinncinnati, OH

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Systemic JIA and canakinumab

Session Information

Date: Tuesday, November 15, 2016

Session Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects II: Juvenile Arthritis

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

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) in Day 15 and 30 respectively in previous studies¹. However, 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 (≥2 to <20 years) 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 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 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: CAN treatment was associated with rapid response and sustained therapeutic effect over the long-term in the pts with active SJIA. The safety profile is consistent with other CAN studies. References: 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. I. Brunner, Novartis, Roche,Pfizer, UCB, Celgene, Regeneron, Amgen, Astrazeneca, GSK and BMS, 5,Novartis and Roche, 8; N. Ruperto, Abbott, BMS, "Francesco Angelini", GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma and Wyeth, 2,Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Boehringer, BMS, CDPharma, Celgene, CrescendoBio, EMD Serono,Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda and Ver, 8; P. Quartier, Abbvie, Novartis, Pfizer, Chugai-Roche, 2,Abbvie, Novartis, Sobi, Roche, 5,Abbvie, Novartis, Pfizer, Roche, Sobi, 8,clinical trials for Abbvie, BMS, Novartis, Pfizer, Roche, Sobi, 9; T. Constantin, None; E. Alexeeva, Roche, Abbott, Novartis, Pfizer, Bristol-Myers Squibb and Centocor, 2,Roche, Novartis, Merck Sharp Dohme, Bristol-Myers Squibb, Medac and Pfizer, 8; I. Koné-Paut, SOBI, Novartis and Roche, 2,Novartis, SOBI, Pfizer, Abbvie and Roche/Chugai, 5; K. Marzan, Novartis, Abbvie, 2; N. Wulffraat, Novartis Pharmaceutical Corporation, 2; R. Schneider, None; S. Padeh, None; V. Chasnyk, None; C. Wouters, GSK, Novartis and Roche, 2; J. B. Kuemmerle-Deschner, Novartis, 2,Novartis, SOBI, Baxalta, 5; T. Kallinich, Novartis, 2,Sobi, Novartis, BMS and Roche, 8; B. Lauwerys, None; E. Haddad, None; E. L. Nasonov, None; M. Trachana, Novartis, Abbvie, Bristol Meyers, 2,Novartis, Roche and Pfizer, 5; O. Vougiouka, None; K. Leon, Novartis Pharmaceutical Corporation, 3; E. Vritzali, Novartis, 3; K. Lheritier, Novartis Pharmaceutical Corporation, 1,Novartis Pharmaceutical Corporation, 3; A. Martini, Abbott, Abbvie, Amgen, Biogenidecm Bristol MyersSquibb, Astellas, Behringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier and Takeda, 8,Abbott, BMS, "Francesco Angelini", GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma and Wyeth, 2; D. J. Lovell, National Institutes of Health, 2,Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UCB, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene and Jannsen, 5,Genentech, Roche and Novartis, 8.

To cite this abstract in AMA style:

Brunner HI, 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 DJ. 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. 2016; 68 (suppl 10). 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/. Accessed July 23, 2019.

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