POS1330 SAFETY OF ANAKINRA IN PATIENTS WITH CRYOPYRIN ASSOCIATED PERIODIC SYNDROMES (CAPS) USING A GRADUATED PRE-FILLED SYRINGE

Background: Cryopyrin associated periodic syndromes (CAPS) are a group of ultra-rare autoinflammatory diseases caused by mutations in the NLRP3 gene, leading to overproduction of IL-1β. CAPS includes the following subdiagnoses: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological cutaneous articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID), where FCAS is the mildest form of CAPS and CINCA/NOMID the most severe. A graduated pre-filled syringe of the IL-1 receptor antagonist anakinra was introduced to meet the need of smaller and varying doses when treating children with CAPS. Objectives: To evaluate the safety of anakinra in CAPS patients using the novel pre-filled syringe. Methods: Investigators managing patients with CAPS treated with anakinra were identified via the Eurofever registry. Follow-up data of at least 3 years for each patient were prospectively collected and analyzed (EUPAS6366). The primary study endpoints were the occurrence of adverse events (AEs) with focus on serious infections, malignancies, injection site reactions, allergic reactions and medication errors, including re-use of the syringe. Secondary endpoints included dose at specific time points, discontinuations, and switch to other IL-1 blocking treatment. Results: 12 patients with CAPS were included in the study, 8 with MWS, 2 with FCAS and 2 with CINCA/NOMID. The majority were male (75%) and white (83.3%). At baseline, all but one patient were already using the graduated prefilled syringe with anakinra. 5 patients required a median dose of 2 to 3 mg/kg/day and 6 patients below 2 mg/kg/day. During a total of 26.1 patient years of treatment, there were 7 AEs with rate of 26.8 (95% CI 4.2-169.6) per 100 patient years. All AEs were infections from 1 patient with CINCA/NOMID and were considered unrelated to anakinra by the investigator. Two of the AEs were considered serious as hospitalization was required (1 tonsillitis and 1 urinary tract infection). No AEs were severe, 6 of the AEs were of moderate severity and 1 was of mild severity. In total, 6 patients discontinued anakinra permanently, 2 during the first year of treatment, 3 during the second year and 1 after the third year of follow-up. The reasons for discontinuation included switch to canakinumab (4 patients), switch to canakinumab and inefficacy (1 patient) and non-compliance (1 patient). The remaining 5 patients continued anakira until the end of the study. 1 patient discontinued anakinra temporarily during the second year of treatment due to non-compliance. No deaths, malignancies, injection site reactions, allergic reactions or medication errors, including re-use of the pre-filled syringe, were observed. Conclusion: The results of the present study confirm the safety profile of anakinra treatment in CAPS patients using the graduated pre-filled syringe. No new safety findings were identified. Disclosure of Interests: Riccardo Papa: None declared, Gabriella Giancane: None declared, Helen J. Lachmann: None declared, Paul Brogan: None declared, Elizabeth Legger: None declared, Daniel Lindqvist Shareholder of: Sobi employee and holder of Sobi shares, Speakers bureau: Sobi employee and holder of Sobi shares, Paid instructor for: Sobi employee and holder of Sobi shares, Consultant of: Sobi employee and holder of Sobi shares, Grant/research support from: Sobi employee and holder of Sobi shares, Employee of: Sobi employee and holder of Sobi shares, Susanna Cederholm Shareholder of: Sobi employee and holder of Sobi shares, Speakers bureau: Sobi employee and holder of Sobi shares, Paid instructor for: Sobi employee and holder of Sobi shares, Consultant of: Sobi employee and holder of Sobi shares, Grant/research support from: Sobi employee and holder of Sobi shares, Employee of: Sobi employee and holder of Sobi shares, Francesca Bagnasco: None declared, Nicolino Ruperto: None declared, Marco Gattorno: None declared