Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose :
Systemic juvenile idiopathic arthritis (sJIA) is an interleukin-1β (IL-1β)-mediated autoinflammatory disease. Canakinumab is a selective, fully human, anti-IL-1β monoclonal antibody. Two pivotal phase 3 trials evaluated the efficacy and safety of canakinumab in patients (pts) with active sJIA with fever.
Methods :
Pts aged 2–19 yrs with active sJIA (fever, ≥2 active joints, C-reactive protein >30 mg/L) with inadequate response to standard of care treatments (NSAIDs, steroids, MTX) were enrolled. Trial 1 was a 4-wk, double-blind, single-dose study of pts randomized to subcutaneous (SQ) canakinumab 4 mg/kg or placebo. Trial 2 enrolled 177 pts, including eligible pts rolling over from Trial 1. In Part I of Trial 2, pts received open-label (OL) canakinumab 4 mg/kg/4wks SQ for up to 32 wks. Pts with an adapted ACR Pediatric 30 criteria response (aACR-Ped30) at the end of Part I entered Part II after randomization 1:1 to continue canakinumab or receive placebo until 37 flare events occurred. The primary endpoint of Trial 1 was the proportion of aACR-Ped30 responders at Day 15. The primary endpoint of Trial 2 in Part I was the proportion of steroid-treated pts at entry who successfully tapered steroids, and in Part II the time to flare. Pts withdrawn due to protocol-driven discontinuation rules were offered participation in the currently on-going OL long-term extension study.
Results :
In Trial 1, 84 pts (canakinumab n=43; placebo, n=41) were enrolled. At Day 15, of the 84 pts, significantly more pts in the canakinumab group (83.7% [36/43]) vs. the placebo group (9.8% [4/41]) achieved an aACR-Ped30 response (P <0.0001). In Trial 2, 177 pts received canakinumab in Part I, 100 of whom were randomized in Part II (canakinumab, n=50; placebo, n=50) and 77 discontinued. During Part I of Trial 2, 44.5% (57/128) of the steroid-treated pts successfully tapered steroids (P <0.0001), with the mean steroid dose lowered to 0.05 mg/kg/d from 0.34 mg/kg/d. Of note, 32.8% (42/128) of the pts stopped steroids completely. In Part II, the median time to flare on placebo was 236 days vs. not observed with canakinumab, corresponding to a statistically significant 63% relative risk reduction of flares (HR 0.37; 95% CI 0.17–0.78; P=0.0043). Inactive disease was achieved by 30.9% (54/175) of the canakinumab-treated pts at the end of Part I and 62% (31/50) upon completion of Part II. 142 (80.2%) of the enrolled pts from Trial 2 entered the OL extension study, which included 48 pts who had withdrawn from the Part I due to efficacy related protocol-driven discontinuation. In both trials, infections were the most common type of adverse event (AE) reported. Most Serious AEs were associated with infections, disease flare, and macrophage activation syndrome (MAS, n=7, including 2 on placebo). Two deaths were reported (1 canakinumab, 1 placebo), both associated with MAS.
Conclusion :
These data support that canakinumab is an effective treatment for active sJIA with fever. Canakinumab demonstrated superior efficacy vs. placebo, allowed successful reduction of steroid use, and significantly decreased the risk of sJIA flares, while demonstrating an acceptable safety profile.
Disclosure:
H. Brunner,
Novartis, UCB, Genentech, Jansen, GSK and Medimmune,
5;
N. Ruperto,
Abbott, Astrazeneca, Bristol Myers and Squibb, Centocor Research & Development, Eli Lilly and Company, ,
2,
Astrazeneca, Novartis, Bristol Myers and Squibb, Roche, Janssen Bilogics B.V.,
8,
“Francesco Angelini” s.p.a, Glaxo Smith & Kline, Italfarmaco, Merck Serono, Novartis, Pfizer Inc., Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc.,
2;
P. Quartier,
Novartis, Abbott and Pfizer ,
2,
Novartis, Roche, Pfizer, Abbott and BMS,
5;
T. Constantin,
None;
N. Wulffraat,
Advisory board NovartisTrials,
5;
G. Horneff,
Abbott, Pfizer,
5,
Abbott, Pfizer, Novartis, Chugai,
6;
R. Brik,
None;
L. McCann,
None;
H. Ozdogan,
Novartis Pharmaceutical Corporation,
8;
L. Rutkowska-Sak,
Reimbursement for patients enrolled in the clinical trial,
2;
R. Schneider,
Hoffmann La-Roche,
5,
Hoffmann La-Roche,
8,
Innomar Strategies,
9;
Y. Berkun,
None;
I. Calvo,
None;
M. Erguven,
Novartis Pharmaceutical Corporation,
5;
L. Goffin,
From Novartis for enrolled patients reimbursement,
5, 9,
Grant for continuous medical education,
9;
M. Hofer,
None;
T. Kallinich,
Novartis Pharmaceutical Corporation,
8;
K. Lheritier,
Novartis Pharmaceutical Corporation,
1,
Full-time employee of Novartis,
3;
K. Abrams,
Novartis Pharmaceutical Corporation,
1,
Full-time employee of Novartis,
3;
A. Stancati,
Full-time Novartis employee,
3;
D. J. Lovell,
Astra-Zeneca, Centocor, Bristol Meyers Squibb, Abbott, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UBC, Xoma, Genentech,
5,
Wyeth Pharmaceuticals,
8,
Amgen, Forest Research,
9,
Arthritis & Rheumatism,
9;
A. Martini,
Abbott, Astrazeneca, Bristol Myers and Squibb, Centocor Research & Development, Eli Lilly and Company, ,
2,
Astrazeneca, Novartis, Bristol Myers and Squibb, Glaxo Smith & Kline,
8,
“Francesco Angelini” s.p.a, Glaxo Smith & Kline, Italfarmaco, Merck Serono, Novartis, Pfizer Inc., Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc.,
2.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-canakinumab-in-patients-with-active-systemic-juvenile-idiopathic-arthritis-and-fever-results-from-two-pivotal-phase-3-trials/