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

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.

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Correspondence to M Fink.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( https://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.

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Gautier, A., Lowe, P., Skerjanec, A. et al. P02-026 - Model-based characterization of the PKPD relationship for canakinumab in CAPS: a step towards personalized. Pediatr Rheumatol 11, A133 (2013). https://doi.org/10.1186/1546-0096-11-S1-A133

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Keywords

  • Clinical Response
  • Pediatric Population
  • Human Monoclonal Antibody
  • Binding Model
  • Binding Parameter