Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Cryopyrin-associated periodic syndrome (CAPS), comprises of extremely rare, inherited auto-inflammatory diseases, including the mildest form familial cold auto-inflammatory syndrome (FCAS), the more severe Muckle-Wells syndrome (MWS), and the most severe form chronic infantile neurologic cutaneous and articular syndrome/neonatal onset multisystem inflammatory disease (NOMID).1 Canakinumab (CAN), a high-affinity fully human monoclonal antibody of the IgG1/k isotype, is designed to bind and functionally neutralize the bioactivity of interleukin 1β (IL-1β); recognized as one of the principal pro-inflammatory cytokines in CAPS.2 The objectives of the study were: 1) to describe the pharmacokinetics (PK) of CAN and pharmacodynamics (PD) of binding IL-1β in CAPS patients; 2) to determine if PK, PD are different in 2- and 3-year-old children compared with older children and adults; and 3) to explore the impact of CAPS phenotype on the PK of CAN and PD of binding to IL-1β.
Methods: A mathematical PK-binding model was developed to describe the kinetics of CAN and binding dynamics of IL-1β patients with CAPS, other auto-inflammatory diseases and healthy volunteers. The subgroup of 7 CAPS patients who were 2 and 3 years of age at baseline was also compared with 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 age and with the severity of the CAPS phenotype. In these youngest patients, MWS and especially NOMID patients had higher concentrations of the inert CAN/IL-1β complexes after administration of CAN, indicating more cytokine in the body to be captured.
Conclusion:
Conclusions: Correlation with clinical responses suggested that these increased levels of IL-1β may explain why younger and especially NOMID phenotype patients require escalation to higher CAN doses.3
References: 1. Kuemmerle-Deschner JB., et al. Arthritis ResTher 2011, 13:R34, 2. Hoffman HM, et al. Arthritis Rheum 2008; 58:2443–2452, 3. Lachmann HJ, et al. Arthritis Rheum 2012; 68 (10), S320
Disclosure:
A. Gautier,
Novartis Pharma AG,
3;
P. Lowe,
Novartis Pharma AG,
3,
Novartis Pharma AG,
1;
A. Skerjanec,
Novartis Pharma AG,
3;
P. McKernan,
Novartis Pharma AG,
3,
Novartis Pharma AG,
1;
W. Wang,
Novartis Pharmaceutical Corporation,
3;
O. Luttringer,
Novartis Pharma AG,
3,
Novartis Pharma AG,
1.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/model-based-pharmacokinetics-of-canakinumab-and-pharmacodynamics-of-il-1beta-binding-in-cryopyrin-associated-periodic-syndromes-a-step-towards-personalized-medicine/