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  • Open Access

Predictors of response in patients with active systemic JIA (SJIA) receiving canakinumab: an exploratory analysis of pooled 12-week data

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Pediatric Rheumatology201412 (Suppl 1) :O12

https://doi.org/10.1186/1546-0096-12-S1-O12

  • Published:

Keywords

  • Multivariate Logistic Regression Analysis
  • Active Joint
  • Full Time Employee
  • Inactive Disease
  • Forest Research Institute

Introduction

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).

Objectives

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), 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 1).
Table

Inactive Disease - Multivariate logistic regression analysis on 12-week data

Variable*, Odds Ratio (95% CI)

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 CAN-naïve patients with normal CRP (i.e. ≤10 mg/l) at Day 15, lower baseline steroid doses, low number of active joints, no prior anti-TNF or prior NSAID use are those most likely to achieve inactive disease up to 12 weeks.

Disclosure of interest

N. Ruperto Grant / Research Support from: To Gaslini Hospital: 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., Speaker Bureau of: Astrazeneca, Bristol Myers and Squibb, Janssen Biologics B.V., Roche, Wyeth, Pfizer, H. Brunner Consultant for: Novartis, Genentech, Pfizer, UCB, AstraZeneca, Biogen, Boehringer-Ingelheim, Regeneron, Paid Instructor for: Novartis, Speaker Bureau of: Novartis, Genentech, I. Kone-Paut Grant / Research Support from: SOBI, Chugai, Consultant for: Pfizer, SOBI, Novartis, AbbVie, Cellgene, Chugai, B. Magnusson: None declared., S. Ozen Consultant for: Novartis (Turkey), Speaker Bureau of: Speaker’s fee from SOBI, F. Sztajnbok Grant / Research Support from: Institutional grant (UERJ) for participating in the canakinumab trial., Speaker Bureau of: Novartis-Brasil, J. Anton Consultant for: Novartis, Speaker Bureau of: Novartis, J. Barash Grant / Research Support from: Investigator in the Canakinumab study sponsored by Novartis, F. Corona: None declared., K. Lheritier Shareholder of: Novartis, Employee of: Novartis Pharma AG, C. Gaillez Employee of: Novartis Pharma AG, A. Martini Grant / Research Support from: Bristol Myers and Squibb, Centocor Research & Development,Glaxo Smith & Kline, Novartis, Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, I declare that the Gaslini Hospital which is the public Hospital where I work as full time employee has received contributions to support the PRINTO research activities from the industries above mentioned. OLD: Francesco Angelini S.P.A., Janssen Biotech Inc, Abbott. , Consultant for: Bristol Myers and Squibb, Centocor Research & Development, Glaxo Smith & Kline, Novartis, Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, I declare that the Gaslini Hospital which is the public Hospital where I work as full time employee has received contributions to support the PRINTO research activities from the industries above mentioned. , Speaker Bureau of: Abbott, Bristol Myers Squibb, Astellas, Boehringer, Italfarmaco, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier, D. Lovell Grant / Research Support from: National Institutes of Health- NIAMS , Consultant for: Astra-Zeneca, Centocor, Amgen, Bristol Meyers Squibb, Abbott, Pfizer, Regeneron, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Speaker Bureau of: Novartis, Roche.

Authors’ Affiliations

(1)
PRINTO-Istituto Gaslini, Genova, Italy
(2)
PRCSG, Cincinnati, USA
(3)
Novartis Pharma AG, Basel, Switzerland

Copyright

© Ruperto et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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