FRI0486 LONG-TERM EFFICACY AND SAFETY OF CANAKINUMAB IN PATIENTS WITH AUTOINFLAMMATORY PERIODIC FEVER SYNDROMES – FIRST INTERIM ANALYSIS OF THE FMF/TRAPS/HIDS SUBGROUPS FROM THE RELIANCE REGISTRY
Authors: J. Henes, J. B. Kuemmerle-Deschner, M. Borte, I. Foeldvari, G. Horneff, T. Kallinich, B. Kortus-Goetze, F. Weller-Heinemann, J. Weber-Arden, N. Blank
Journal: Annals of the Rheumatic Diseases (2020)

Background: Autoinflammatory periodic fever syndromes characterized by excessive interleukin(IL)-1b release and severe systemic and organ inflammation have been successfully treated with the anti-IL-1 inhibitor canakinumab (CAN). In clinical trial situations and real life, rapid remission of symptoms and normalization of laboratory parameters were observed in most patients. 1-3 Objectives: The present study explores long-term effectiveness and safety of CAN under routine clinical practice conditions in pediatric and adult patients with CAPS (cryopyrin-associated periodic syndromes), FMF (familial Mediterranean fever), TRAPS (tumor necrosis factor receptor-associated periodic syndrome) and HIDS/MKD (hyperimmunoglobulinemia D syndrome/mevalonate kinase deficiency). Methods: RELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a 3-year follow-up period. Pediatric (age ≥2 years) and adult patients with clinically confirmed diagnoses of CAPS, FMF, TRAPS and HIDS/MKD that routinely receive CAN are enrolled in order to evaluate effectiveness and safety of CAN in clinical routine. Results: This first interim analysis of patient subgroups diagnosed with FMF, HIDS and TRAPS includes baseline data of 41 patients (10 TRAPS, 2 HIDS, 29 FMF), including preliminary 6-month data of a FMF-subset (N=16). Evaluation of disease activity and fatigue by patients’ assessment, days absent from school/work, inflammatory markers and physician global assessment (PGA) was performed at baseline and will be further assessed at 6-monthly intervals within the 3-year observation period. Preliminary results of a first subset of 16 patients diagnosed with FMF are available and indicate stable remission and disease control upon long-term CAN treatment: within the first study interval, no major changes were observed regarding the analyzed parameters (table 1). Table 1. Baseline characteristics of the TRAPS/HIDS/FMF-subgroups and preliminary 6-month data of FMF subset. TRAPS HIDS FMF Baseline Baseline Baseline all FMF patients Baseline FMF subset 6 months FMF subset Number of patients, N 10 2 29 16 16 Mean age, years (SD) 22 (4; 43) 11 (5; 18) 26 (5; 56) 16 (5; 47) 16 (5; 47) Female (%), N=9 (1 missing) 5 (56) 1 (50) 15 (52) 7 (44) 7 (44) Mean duration of prior canakinumab treatment, years (min; max) 1 (0; 2) 3 (2; 4) n. a. 2.2 (0; 6) 2.2 (0; 6) Patient’s assessment of disease activity 0-10, mean (min; max) 2.1 (0; 5) 0 (0; 0) 3 (0; 10) 2.8 (0; 8) 2.2 (0; 7) Patient’s assessment of fatigue 0-10 3.4 (0; 8) 0 (0; 0) 4.4 (0; 9) 4.6 (0; 9) 3.9 (0; 8) Number (%) of patients with days absent from school/work due to study indication during last 6 months 4 (44) 2 (100) 5 (17) 2 (13) 5 (31) Inflammatory markers, CRP/SAA, mean (mg/dL) 2.0 7.9 0.1 0.6 0.9 5.3 0.5 2.4 0.6 2.4 PGA of disease activity: no/mild to moderate/severe; N (%)* 1 (11) 6 (67) 0 (0) 2 (100) 0 (0) 0 (0) 10 (35) 8 (28) 2 (7) 5 (31) 7 (44) 1 (6) 6 (38) 7 (44) 0 (0) SAE, N (%) 0 (0) 0 (0) 2 (6.9) n. a. 2 (12.5) Conclusion: Baseline characteristics of all subgroups and first interim data of FMF patients are available from the RELIANCE study, the longest running real-life CAN registry. Further interval data will be analyzed to assess efficacy and safety of long-term CAN-treatment in patients with autoinflammatory periodic fever syndromes. References: [1]Lachmann et al. N Engl J Med. 2009;360(23):2416-25 [2]Kuemmerle-Deschner et al. Rheumatology (Oxford). 2016;55(4):689-96 [3]De Benedetti et al. N Engl J Med. 2018;378(20):1908-1919 Disclosure of Interests: Jörg Henes Grant/research support from: Novartis, Roche-Chugai, Consultant of: Novartis, Roche, Celgene, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim,, J. B. Kuemmerle-Deschner Grant/research support from: Novartis, AbbVie, Sobi, Consultant of: Novartis, AbbVie, Sobi, Michael Borte Grant/research support from: Pfizer, Shire, Ivan Foeldvari Consultant of: Novartis, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Tilmann Kallinich Grant/research support from: Novartis, Consultant of: Sobi, Roche, Novartis, Birgit Kortus-Goetze Consultant of: Novartis, Frank Weller-Heinemann: None declared, Julia Weber-Arden Employee of: I am employed by Novartis, Norbert Blank Grant/research support from: Novartis, Sobi, Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche