Volume 11 Supplement 1

7th Congress of International Society of Systemic Auto-Inflammatory Diseases (ISSAID)

Open Access

P02-026 - Model-based characterization of the PKPD relationship for canakinumab in CAPS: a step towards personalized

  • A Gautier1,
  • P Lowe1,
  • A Skerjanec1,
  • P McKernan1,
  • O Luttringer1 and
  • M Fink1
Pediatric Rheumatology201311(Suppl 1):A133

https://doi.org/10.1186/1546-0096-11-S1-A133

Published: 8 November 2013

Introduction

Canakinumab is a high-affinity fully human monoclonal antibody of the IgG1/k isotype, designed to bind and functionally neutralize the bioactivity of IL-1β, which is recognized as one of the principal pro-inflammatory cytokines in cryopyrin associated periodic syndromes (CAPS).

Objectives

The objectives of the study were to describe the kinetics of canakinumab and dynamics of binding IL-1β in CAPS patients; to determine if these are different in 2- and 3-year-old children versus older children and adults; and to explore the impact of CAPS phenotype (Muckle-Wells Syndrome [MWS], Familial Cold Autoinflammatory Syndrome [FCAS], Neonatal-Onset Multisystem Inflammatory Disease [NOMID]) on the kinetics of canakinumab and dynamics of binding to IL-1β.

Methods

A pharmacokinetics (PK)-binding model was used to describe the kinetic and binding parameters of canakinumab and IL-1β in CAPS patients, and in other populations relative to CAPS. The subgroup of 7 CAPS patients who were 2 and 3 years of age at baseline was also compared to the overall CAPS population.

Results

The 7 CAPS patients did not show any difference in terms of PK. However, they showed a higher IL-1β turnover including IL-1β clearance and production. IL-1β levels were linked with the severity of the CAPS phenotype. In the pediatric population, MWS and especially NOMID patients had higher concentrations of the inert canakinumab/IL-1β complexes after administration of canakinumab, indicating more cytokine in the body to be captured.

Conclusion

Correlation with clinical responses suggested that these increased levels of IL-1β may explain why younger and NOMID phenotype patients require higher doses or escalation to higher doses.

Disclosure of interest

  1. A.

    Gautier Shareholder of: Novatis Pharma AG, Employee of: Novatis Pharma AG, P. Lowe Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, A. Skerjanec Employee of: Novartis Pharma AG, P. McKernan Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, O. Luttringer Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, M. Fink: None Declared.

     

Authors’ Affiliations

(1)
Novartis Pharma AG

Copyright

© Gautier et al; licensee BioMed Central Ltd. 2013

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/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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