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Open Access Research article

Canakinumab (ACZ885, a fully human IgG1 anti-IL-1β mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS)

Jasmin B Kuemmerle-Deschner1*, Eduardo Ramos2, Norbert Blank3, Joachim Roesler4, Sandra D Felix5, Thomas Jung5, Kirstin Stricker6, Abhijit Chakraborty7, Stacey Tannenbaum8, Andrew M Wright9 and Christiane Rordorf5

Author Affiliations

1 Division of Pediatric Rheumatology, Department of Pediatrics, University Children's Hospital Tuebingen, Hoppe-Seyler-Strasse 1, 72076 Tübingen, Tuebingen, Germany

2 Department of Pediatrics, Hospital Central de Asturias, Julian Claveria s/n, 33006 Oviedo, Spain

3 Medizinische Klinik 5, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, D-69120, Heidelberg, Germany

4 Department of Pediatrics, Universitäts-Klinikum Carl-Gustav-Carus, Fetscherstr. 74, 01307 Kinderklinik, Dresden, Germany

5 Translational Medicine, Novartis Institutes for BioMedical Research, Basel CH-4002, Switzerland

6 Development, Novartis Pharma, Basel CH-4002, Switzerland

7 Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, East Hanover, NJ 07936-1080, USA

8 Modeling and Simulation, Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, USA

9 Clinical Information Sciences, Novartis Pharma, Basel CH-4002, Switzerland

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Arthritis Research & Therapy 2011, 13:R34  doi:10.1186/ar3266

Published: 28 February 2011

Abstract

Introduction

Cryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1β) release. CAPS is a rare hereditary auto-inflammatory disease, which may start early in childhood and requires a life-long treatment. Canakinumab, a fully human anti-IL-1β antibody, produces sustained selective inhibition of IL-1β. This study was conducted to assess the efficacy, safety, and pharmacokinetics of canakinumab in the treatment of pediatric CAPS patients.

Methods

Seven pediatric patients (five children and two adolescents) with CAPS were enrolled in a phase II, open-label study of canakinumab in patients with CAPS. Canakinumab was administered at a dose of 2 mg/kg subcutaneously (s.c.) (for patients with body weight ≤ 40 kg) or 150 mg s.c. (for patients with body weight > 40 kg) with re-dosing upon each relapse. The primary efficacy variable was time to relapse following achievement of a complete response (defined as a global assessment of no or minimal disease activity and no or minimal rash and values for serum C-reactive protein (CRP) and/or serum amyloid A (SAA) within the normal range, < 10 mg/L).

Results

All patients achieved a complete response within seven days after the first dose of canakinumab and responses were reinduced on retreatment following relapse. Improvements in symptoms were evident within 24 hours after the first dose, according to physician assessments. The estimated median time to relapse was 49 days (95% CI 29 to 68) in children who received a dose of 2 mg/kg. Canakinumab was well tolerated. One serious adverse event, vertigo, was reported, but resolved during treatment.

Conclusions

Canakinumab, 2 mg/kg or 150 mg s.c., induced rapid and sustained clinical and biochemical responses in pediatric patients with CAPS.

Trial registration number

ClinicalTrials.gov: NCT00487708