Efficacy and Safety of Canakinumab in Children with Systemic Juvenile Idiopathic Arthritis: Results from the Phase 3 Extension Study

Hermine I. Brunner¹, Nicolino Ruperto², Pierre Quartier³, Tamas Constantin², Ekaterina Alexeeva², Isabelle Koné-Paut², Katherine Marzan¹, Nico Wulffraat², Rayfel Schneider¹, Shai Padeh², Vyacheslav Chasnyk², Carine Wouters², Jasmin B. Kuemmerle-Deschner², Tilmann Kallinich², Bernard Lauwerys⁴, Elie Haddad¹, Evgeny Nasonov², Maria Trachana², Olga Vougiouka², Karolynn Leon⁵, Antonio Speziale⁶, Karine Lheritier⁶, Alberto Martini², Daniel Lovell^1,7 and on behalf of PRINTO/PRCSG, ¹PRCSG, Cincinnati, OH, ²PRINTO-Istituto Gaslini, Genova, Italy, ³Necker-Enfants Malades Hospital, Paris, France, ⁴Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium, ⁵Novartis Pharmaceuticals Corporation, East Hanover, NJ, ⁶Novartis Pharma AG, Basel, Switzerland, ⁷Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Meeting: ACR/ARHP Annual Meeting 2015

Date of first publication: September 29, 2015

Keywords: Systemic JIA and interleukins (IL)

Session Information

Date: Tuesday, November 10, 2015

Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects Posters (ACR): Imaging and Novel Clinical Interventions

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:
Systemic juvenile idiopathic
arthritis (SJIA) is a debilitating form of arthritis associated with systemic
symptoms such as anemia, rash, leukocytosis, elevated erythrocyte sedimentation
rate and acute-phase reactants. High and spiking fevers are also features of
the disease. Canakinumab (CAN) leads to improvement for patients (pts) with
SJIA exhibiting articular and systemic features at treatment onset.¹However,
little is known about the long-term safety and efficacy in CAN-naïve pts,
including those who may not exhibit systemic fever. Here we present the long-term efficacy and safety profile
of CAN in SJIA pts with and without fever at CAN initiation.

Methods: Pts aged 2-20 years with SJIA with and without SJIA
associated fever at enrollment received open-label
CAN 4mg/kg s.c. every 4 weeks. Efficacy was assessed every 3 months by adapted JIA ACR
response criteria (aACR/JIA); juvenile arthritis disease activity score
[JADAS]; clinical inactive disease; clinical remission on medication [CRM, 6
months continuous clinical inactive disease]. Safety was assessed monthly.

Results: Of 123 pts, 70
(57%) with and 52 (42%) without SJIA associated fever, were available for
analysis with a median study duration of 96 weeks. At Week 4, 73% and 81% of pts
with and without fever at study entry, respectively had ≥ aACR/JIA30,
increasing to 89% and 92% at Wk12. At Week 2, 23.9% and 24.5% of pts with and
without fever at study entry, respectively, had inactive disease which
increased to 61.5% and 59.5%, respectively, at Week 32 and thereafter. CRM was
achieved in 42.3% of pts in the overall group with 26.8% maintaining it for 12
consecutive months. Median JADAS27-CRP and JADAS10-CRP scores were 6.0 (suggesting
moderate disease activity) at Day 15 and 1.5 (indicating low disease activity)
at the last assessment, respectively. The disease activity status at baseline
and end of study for JADAS10-CRP and JADAS27-CRP are presented in Table. Adverse
events (AEs) were reported in 63 (90%) and 45 (86.5%) pts with and without
fever, respectively. Serious AEs were reported in 24 (34.3%) and 16 (30.8%)
pts with and without fever, respectively. Overall, 8 events of MAS (pts with
fever, n=6; pts without fever, n=2) were reported in both the groups. No deaths
were reported during the study. No new safety signals were observed in the
subgroup.

Table . Disease
activity states based on JADAS27-CRP and JADAS10-CRP

	Disease state, %	SJIA patients, N=123
		Fever at baseline
		Yes (n=70)		No (n=52)
		Baseline n=68	Last assessment n=70	Baseline n=52	Last assessment n=51
JADAS10-CRP	ID	0	50	0	47.1
	LDA	0	12.9	0	9.8
	MDA	10.3	5.7	9.6	19.6
	HDA	89.7	31.4	90.4	23.5
JADAS27-CRP	ID	0	50	0	47.1
	LDA	0	12.9	0	9.8
	MDA	8.8	2.9	7.7	15.7
	HDA	91.2	34.3	92.3	27.5
Cut-off values for inactive disease (ID), low disease activity (LDA) , moderate disease activity (MDA), and high disease activity (HDA), respectively for JADAS10: ≤1, >1– ≤3.8, >3.8 – ≤10.5, and >10.5; and JADAS27: ≤1, >1 – ≤ 3.8, >3.8 – ≤8.5, and >8.5

Conclusion: Canakinumab provides similar long-term efficacy in
SJIA pts, irrespective of presence of systemic fever at treatment onset. The
safety profile was acceptable and similar to the pivotal program in SJIA pts with
fever at enrollment.

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

Disclosure: H. I. Brunner, Novartis, Roche, Pfizer, UCB, Celgene, Regeneron, Amgen, Astrazeneca, GSK, BMS, 5,Novartis, Roche, 8; N. Ruperto, Abbott, BMS, "Francesco Angelini", GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, 2,Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Boehringer, BMS, CD-Pharma,Celgene, CrescendoBio, EMD Serono,Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, Vertex, 8; P. Quartier, Abbvie, BMS, Chugai-Roche, Novartis, Pfizer, SOBI, 2,Abbvie, Novartis, Servier, SOBI, 5,Abbvie, BMS, Chugai-Roche, Medimmune, Novartis, Pfizer, SOBI, 8; T. Constantin, None; E. Alexeeva, Roche, Abbott, Novartis, Pfizer, Bristol-Myers Squibb, Centocor, 2,Roche, Novartis, Merck Sharp Dohme, aBristol-Myers Squibb, Medac, Pfizer, 8; I. Koné-Paut, Novartis, SOBI Biovitrum, Pfizer, Abbvie, Roche/Chugai, 5,Novartis, Pfizer, 9,Novartis, 9,To my institution: SOBI, Novartis, Roche, 2; K. Marzan, Novartis and Abbvie, 2; N. Wulffraat, Novartis, 2; R. Schneider, Novartis, Novimmune, Sobi, Innomar Strategies, 5; S. Padeh, None; V. Chasnyk, None; C. Wouters, GSK, Novartis, Roche, 2; J. B. Kuemmerle-Deschner, Novartis Pharmaceutical Corporation, 8,Novartis and Sobi, 5; T. Kallinich, None; B. Lauwerys, None; E. Haddad, None; E. Nasonov, None; M. Trachana, Novartis, Roche, Pfizer, 5,Novartis, Abbvie, Bristol Meyers, 2; O. Vougiouka, None; K. Leon, Novartis Pharmaceutical Corporation, 3; A. Speziale, Novartis, 3; K. Lheritier, Novartis, 1,Novartis, 3; A. Martini, Abbott, BMS, "Francesco Angelini", GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, 2,Abbott, Abbvie, Amgen, Biogenidecm Bristol MyersSquibb, Astellas, Behringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier, Takeda., 8; D. Lovell, National Institutes of Health, 2,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, 5,Genentech, Roche, 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 E, Trachana M, Vougiouka O, Leon K, Speziale A, Lheritier K, Martini A, Lovell D. Efficacy and Safety of Canakinumab in Children with Systemic Juvenile Idiopathic Arthritis: Results from the Phase 3 Extension Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-canakinumab-in-children-with-systemic-juvenile-idiopathic-arthritis-results-from-the-phase-3-extension-study/. Accessed .

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