Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
Systemic juvenile idiopathic arthritis (SJIA), an interleukin-1β (IL-1β)-mediated autoinflammatory disease, is characterized by recurrent flares of active disease. Canakinumab (CAN), a selective, human, anti- interleukin-1β monoclonal antibody, has been shown to be efficacious in the treatment of SJIA (Ruperto et al. N Engl J Med 2012). The present study aimed to explore baseline demographics and clinical characteristics that are most predictive of response to CAN in CAN-naïve SJIA patients during the initial 12 weeks of therapy.
Methods
Data from 3 trials were pooled for this analysis. CAN-naïve patients (pts; n=178) aged 2–19 years with active SJIA were enrolled and received sc CAN 4 mg/kg/month; Predictors of response (according to aACR* 30, 70, and Inactive Disease [ID]) at Days (D) 15, 29, 57 and 85 were explored using univariate and multivariate logistic regression analyses. The candidate predictors (categorical variables) of CAN-response considered were: Age group, Gender, Prior NSAIDs (no/yes), Prior MTX (no/yes), Steroids (0, >0 – ≤0.4;> 0.4 mg/kg/day), Number of Active Joints (≤10, 11-≤20, >20) and Joints with Limitation of Motion (≤10, 11-≤20,>20), CRP (elevated/normal) at baseline and at D15. All candidate predictors with p<0.1 in univariate analyses were included in the multivariate analysis. *ACR response plus absence of fever.
Results
By Week 2 there was substantial clinical benefit with 102 pts (57%) and 36 pts (20%) achieving aACR70 and ID, respectively; by Week 12, 108 pts (61%) had aACR70 and 50 pts (28%) ID. The multivariate analysis indicated that normal CRP at D15 is the only predictor significant (all p<0.05) for ID at all time-points (Table).
Table: Inactive Disease – Multivariate logistic regression analysis on 12-week data
|
|
Odds Ratio (95% CI) |
|||
|
Variable* |
Day 15 |
Day 29 |
Day 57 |
Day 85 |
|
CRP at Day 15 (elevated vs normal) |
0.20 (0.07, 0.55) |
0.14 (0.04, 0.41) |
0.26 (0.10, 0.66) |
0.31 (0.12, 0.82) |
|
Number of active joints (11-≤20 vs. ≤10) |
0.22 (0.03, 1.66) |
0.55 (0.09, 3.41) |
0.17 (0.031, 0.97) |
0.37 (0.06, 2.10) |
|
Number of active joints (≤10 vs. >20) |
2.56 (0.12, 55.39) |
1.53 (0.06, 37.44) |
16.10 (1.00, 258.12) |
25.41 (1.60, 404.61) |
|
Prior NSAID treatment (no vs. yes) |
2.01 (0.71, 5.71) |
9.33 (2.44, 35.68) |
3.10 (1.03, 9.31) |
5.31 (1.66, 17.05) |
|
Steroid Level (0 vs. >0.4 mg/kg/day) |
5.48 (0.97, 31.01) |
8.89 (1.26, 62.64) |
2.98 (0.51, 17.46) |
11.16 (1.72, 72.34) |
|
Steroid Level (>0.4 vs >0-≤0.4 mg/kg/day) |
0.32 (0.08, 1.29) |
0.41 (0.09, 1.82) |
0.81 (0.25, 2.60) |
0.13 (0.03, 0.57) |
|
Prior MTX treatment (no vs. yes) |
1.94 (0.75, 5.00) |
2.78 (0.93, 8.33) |
2.79 (1.04, 7.51) |
1.77 (0.65, 4.83) |
|
Prior anti-TNFs treatment (no vs. yes) |
1.83 (0.52, 6.49) |
3.62 (0.77, 17.00) |
2.01 (0.63, 6.38) |
3.64 (1.04, 12.77) |
Values in bold are significant; *Significant in at least one time point
Conclusion This exploratory analysis suggests that canakinumab-naïve patients with normal CRP (i.e. ≤10 mg/l) at Day 15, lower baseline steroid doses, low number of active joints, no prior NSAID use are most likely to achieve inactive disease up to 12 weeks.
Disclosure:
H. I. Brunner,
Novartis, Genentech, Pfizer, UCB, AstraZeneca, Biogen, Boehringer-Ingelheim, Regeneron,
5,
Novartis, Genentech,
8,
Novartis Pharma AG,
9;
N. Ruperto,
Abbott, Astrazeneca, BMS, Centocor Research & Development, Eli Lilly and Company, “Francesco Angelini”, Glaxo Smith & Kline, Italfarmaco, Novartis, Pfizer Inc., Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc.,,
2,
Astrazeneca, Bristol Myers and Squibb, Janssen Biologics B.V., Roche, Wyeth, Pfizer,,
8;
I. Koné-Paut,
SOBI, Chugai,
2,
Pfizer, SOBI, Novartis, AbbVie, Cellgene, Chugai,
5;
B. Magnusson,
None;
S. Ozen,
Novartis (Turkey),,
5,
SOBI,
8;
F. Sztajnbok,
Institutional grant (UERJ) for participating in the canakinumab trial,
2,
Novartis-Brasil,
8;
J. Anton,
Novartis-,
5,
Novartis-,
8;
J. Barash,
Investigator in the Canakinumab study sponsored by Novartis,
2;
R. Berner,
None;
F. Corona,
None;
K. Lheritier,
Novartis .,
3,
Novartis .,
1;
C. Gaillez,
Novartis.,
3;
A. Martini,
Bristol-Myers Squibb,Centocor Research & Development,Glaxo Smith & Kline, Novartis, Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH,
2,
Bristol Myers and Squibb, Centocor Research & Development, Glaxo Smith & Kline, Novartis, Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH,,
5,
Abbott, Bristol Myers Squibb, Astellas, Boehringer, Italfarmaco, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier,,
8;
D. Lovell,
National Institutes of Health- NIAMS,
2,
AstraZeneca, 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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