A2: Rapid and Sustained Response in Patients Suffering From Severe Cryopyrin-Associated Periodic Syndromes Treated With Anakinra (Kineret®)

Background/Purpose: Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of rare inherited autoinflammatory diseases consisting of a spectrum of three conditions: FCAS, Muckle-Wells Syndrome and the most severe form, NOMID. Anakinra was recently approved in the US for treatment of NOMID and in the European Union for treatment of CAPS. The objective of the present analysis is to assess the response rate to anakinra treatment and time to changes in symptom severity after initiation, withdrawal and re-institution of the treatment in patients with severe CAPS. Methods: A prospective, open-label withdrawal design study of anakinra treatment with long-term extension including 43 patients was conducted at the National Institutes of Health (Goldbach-Mansky et al 2006, Sibley et al 2012). The primary efficacy endpoint, the Diary Symptom Sum Score (DSSS) collected daily up to 60 months included 5 symptoms (fever, rash, joint pain, vomiting, headache); each scored from 0 (no symptoms) to 4 (severe symptoms). Earlier data demonstrated that rash and conjunctivitis disappeared in 3 days in all patients, the DSSS was decreased at 3 months and all patients except one met the criteria of a flare during the 7-day withdrawal phase (Goldbach-Mansky et al 2006). In the present analysis, we defined the response as at least 50% improvement from baseline in the weekly average DSSS. The mean changes in DSSS were estimated with Mixed Model for Repeated Measures (MMRM). Results: Twenty nine out of the 43 enrolled patients provided valid DSSS data for the analysis. A majority of the patients were children (17% 80% of the patients met the response criteria. Eleven consecutive patients participated in the withdrawal phase at 3 months of treatment. After treatment withdrawal the average DSSS increased from 0.6 to 5.2 (p