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
OBJECTIVE: To propose a reduced joint power Doppler US (PDUS) assessment and provide preliminary evidence of its validity, feasibility, reliability and sensitivity to change compared with a comprehensive (i.e. 44 joints) PDUS assessment in evaluating synovitis in JIA. METHODS: This multicentre study included 42 children with active JIA with ≥4 clinically involved joints requiring modified therapy. At each visit, clinical and PDUS assessments were performed blinded. Each joint was scored for greyscale (GS) synovitis and power Doppler signal according to a 4-point semiquantitative scale with calculation of US composite indices and US composite joint counts. A process of data reduction based on the frequency of US joint involvement was performed to obtain a reduced PDUS assessment. The relationship between the comprehensive and the reduced PDUS assessments was investigated by Spearman's coefficient at all visits, as well as the relationship between changes in the two PDUS assessments during follow-up. In addition, the metric properties of the comprehensive and the reduced PDUS assessments were tested. RESULTS: The 10-joint PDUS assessment, including bilateral knee, ankle, wrist, elbow and the second MCP joints, detected 100% of children with GS synovitis and power Doppler signal. The two PDUS assessments were highly correlated at all visits. The reduced model had a higher responsiveness than the comprehensive model. Intraobserver and interobserver agreement was good for both US findings. CONCLUSION: The 10-joint PDUS assessment is valid and feasible for assessment of synovitis in JIA in clinical practice.