ABSTRACT
OBJECTIVES: Cryopyrin-associated periodic syndromes (CAPS) are dominantly-inherited autoinflammatory diseases. The uncontrolled IL-1ß overproduction observed in these patients is the rational basis to treat them with anti-IL-1 drugs. The objective of this study was to evaluate the efficacy and safety of treatment with the long-lasting fully humanised anti-IL-1ß monoclonal antibody canakinumab in a Spanish cohort of patients with CAPS. METHODS: Clinical and laboratory data of CAPS patients carrying a heterozygous germline NLRP3 mutation were obtained. The initial treatment scheme with canakinumab was 150 mg/8 weeks administered subcutaneously in adult patients and 2 mg/kg/8 weeks in paediatric patients. RESULTS: Eight unrelated patients were enrolled. Canakinumab was the first anti-IL-1 drug used in three of them; five were already receiving anakinra. The clinical response to the initial canakinumab scheme was positive in all patients, and was quickly observed in the first 24-72 hours. Four required increasing the frequency and/or dose of canakinumab. A limited or no efficacy in those symptoms related to consequence of the deforming arthropathy and neurosensorial deafness was observed. The adverse side effects were restricted to infectious complications in a small percentage of patients. The treatment was well tolerated by all patients, with no reactions at drug site injections. CONCLUSIONS: Canakinumab caused fast and sustained remissions in most clinical and biochemical manifestations in all enrolled patients, with a limited efficacy in the structural lesions. Dose adjustments seem to be necessary for children and/or for patients with the most severe CAPS phenotypes. Treatment was well tolerated with a low incidence of adverse effects.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Cryopyrin-Associated Periodic Syndromes/drug therapy , Immunosuppressive Agents/therapeutic use , Adolescent , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Carrier Proteins/genetics , Child , Child, Preschool , Cryopyrin-Associated Periodic Syndromes/diagnosis , Cryopyrin-Associated Periodic Syndromes/genetics , Cryopyrin-Associated Periodic Syndromes/immunology , Drug Dosage Calculations , Female , Genetic Predisposition to Disease , Germ-Line Mutation , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/immunology , Male , Middle Aged , NLR Family, Pyrin Domain-Containing 3 Protein , Phenotype , Remission Induction , Risk Factors , Spain , Time Factors , Treatment OutcomeABSTRACT
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