ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 931

Response to Canakinumab Treatment Is Maintained in Systemic Juvenile Idiopathic Arthritis Patients

N.M. Wulffraat1,2, N. Ruperto2, H.I. Brunner3, S. Oliveira2, Y. Uziel2, K. Nistala2, R. Cimaz2, M. Ferrandiz2, B. Flato2, M.L. Gamir2, I. Koné-Paut2, C. Gaillez4, K. Lheritier4, K. Abrams5, A. Martini2 and D.J. Lovell3, 1Pediatric Rheumatology, UMC Utrecht, Utrecht, Netherlands, 2PRINTO-Istituto Gaslini, Genova, Italy, 3PRCSG, Cincinnati, OH, 4Novartis Pharma AG, Basel, Switzerland, 5Novartis Pharmaceuticals Corporation, East Hanover, NJ

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects: Juvenile Idiopathic Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Canakinumab, a selective, human, anti-interleukin (IL) -1β monoclonal antibody, is approved for the treatment of systemic juvenile idiopathic arthritis (SJIA) patients (≥ 2 years old). SJIA is an IL-1β-mediated autoinflammatory disease, which is characterized by recurrent flares of active disease. Canakinumab treatment in patients with SJIA, allows for successful steroid dose reduction/discontinuation and reduces risk to experience a flare.1 We evaluated the maintenance of efficacy with continued canakinumab treatment in SJIA patients during the blinded randomized treatment withdrawal part of a large phase III trial.

Methods: Patients 2–19 yrs of age with active SJIA who had responded to open-label canakinumab treatment 4mg/kg/4wks sc, maintained a minimum adapted ACR Pediatric criteria [aACR] 30 for up to 32 weeks, and were steroid-free or had successfully reduced systemic steroids to a minimum dose, were randomized to either continue canakinumab or receive placebo until 37 flare events occurred.1 Patients were considered to have completed the study if they entered clinical remission on medication (CRM), i.e. achieved 24 consecutive weeks of clinical inactive disease (CID).2 A survival analysis of the time to worsening in  aACR level, after randomization for the canakinumab and placebo groups was performed.  Time to worsening is the time to fail to maintain at least the same level of aACR response seen at randomization. The change in the proportion in each group of those with CID was also evaluated.

Results: 100 pts were randomized to a canakinumab (n=50) or a placebo (n=50) group, of whom 26 (53%) and 27 (54%), respectively, had CID at the start of the randomization part. In the first 2 months, probability of maintaining aACR response was similar for both treatment groups. Thereafter, the probability of maintaining aACR response was greater in the canakinumab vs placebo groups. The median time to worsening in aACR level for patients in the placebo group was 141 days (95% CI: 85, 281), and could not be calculated for canakinumab as <50% of canakinumab group had a worsening in their aACR level by the end of this phase.  The median duration of exposure for the canakinumab group was 221.5 days (range: 8-617 days). There was a statistically significant relative risk reduction of 51% for the canakinumab vs placebo group to experience a worsening in aACR level (HR= 0.49; 95% CI: 0.27, 0.90; p=0.0131). CID was achieved by 31 (62.0%) vs 17 (34.0%) patients in canakinumab vs placebo at their last visit (OR= 3.4; 95% CI: 1.5, 8.0; p=0.0020) and CRM was reached by 20 (40%) canakinumab and 2 (4%) placebo patients by the end of the study.

Conclusion: A greater proportion of SJIA patients who continued canakinumab treatment maintained/improved their aACR response, achieved CID and CRM than pts who discontinued canakinumab by being switched to placebo, demonstrating maintenance of efficacy with continued canakinumab treatment over time.

References:

1. Ruperto N, et al. N Engl J Med 2012;367(25):2396–406.

2. Wallace CA, et al. J Rheumatol 2004;31(11):2290-4.

Disclosure:

N. M. Wulffraat,

Abbvie,

2,

Novartis, Pfizer,

5;

N. Ruperto,

To Gaslini Hospital: Abbott, Astrazeneca, BMS, Centocor Research & Development, Eli Lilly and Company, ,

2,

Astrazeneca, Bristol Myers and Squibb, Janssen Biologics B.V., Roche, Wyeth/Pfizer,

8;

H. I. Brunner,

Novartis, Roche, BMS, Pfizer, Biogen, Boehringer-Ingelheim, Jannsen, Astrazaneca,

5,

Novartis, Roche,

8;

S. Oliveira,

Novartis, Roche,

2;

Y. Uziel,

Novartis, ,

5, 9,

Novartis, Pfizer, Roche, Abbvie,

8;

K. Nistala,
None;

R. Cimaz,
None;

M. Ferrandiz,

Novartis Pharmaceutical Corporation,

2;

B. Flato,

Novartis Pharmaceutical Corporation,

2;

M. L. Gamir,
None;

I. Koné-Paut,

SOBI, Chugai,

2,

Pfizer, SOBI, Novartis, Abbvie, Celgene, Chugai,

5;

C. Gaillez,

Novartis Pharmaceutical Corporation,

3;

K. Lheritier,

Novartis Pharmaceutical Corporation,

3,

Novartis Pharmaceutical Corporation,

1;

K. Abrams,

Novartis Pharmaceutical Corporation,

1,

Novartis Pharmaceutical Corporation,

3;

A. Martini,

Abbot, Bristol Myers and Squibb, Francesco Angelini S.P.A, Glaxo Smith and Kine, Janssen Biotech Inc., Novartis, Pfizer Inc., Roche, Sanofi Aventis, Schwarz,

2,

Abbot, Amgen, Biogenidecm Bristol Myers Squibb, Astellas, Bohringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier,

5,

Abbot, Amgen, Biogenidecm Bristol Myers Squibb, Astellas, Bohringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier,

8;

D. J. Lovell,

National Institutes of Health- NIAMS ,

2,

Astra-Zeneca, Centocor, Amgen, Bristol Meyers Squibb, Abbott, Pfizer, Regeneron, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson,

5,

Novartis, Roche,

8.

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