POS1379 LONG-TERM EFFICACY AND SAFETY OF CANAKINUMAB IN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER (FMF) - INTERIM ANALYSIS OF THE RELIANCE REGISTRY
Authors: J. Henes, J. B. Kuemmerle-Deschner, T. Kallinich, F. Dressler, F. Weller-Heinemann, B. Kortus-Goetze, I. Foeldvari, G. Horneff, M. Hufnagel, F. Meier, J. Weber-Arden, N. Blank
Journal: Annals of the Rheumatic Diseases (2021)

Background: Familial Mediterranean Fever (FMF) is characterized by recurrent attacks of fever and serositis as well as elevated inflammatory markers. FMF treatment goals according to EULAR are to control acute attacks and subclinical inflammation and to improve patients´ quality of life 1 . In a phase 3 pivotal study ( CLUSTER study), FMF patients treated with the interleukin-1β inhibitor canakinumab met all these goals 2 . Objectives: The present study explores the long-term efficacy and safety of canakinumab (CAN) in routine clinical practice in pediatric (age ≥2 years) and adult FMF patients. Methods: RELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a three-year follow-up period. Patients with clinically confirmed diagnosis of FMF who routinely receive CAN were enrolled in order to evaluate effectiveness and safety of CAN under standard clinical practice conditions. Disease activity and remission by physicians´ assessment, disease activity, fatigue and impact on social life by patients’ assessment, inflammatory markers and AIDAI (Auto-Inflammatory Diseases Activity Index) score were recorded at baseline and were assessed at 6-monthly intervals within the three-year observation period of the study. Results: This interim analysis of FMF patients (N=54) enrolled by December 2020 includes baseline as well as 6-, 12- and 18-month data. Mean age in this cohort was 25 years (4−56 years) and the proportion of female patients was 46 % (N=25). At baseline, median duration of prior CAN treatment was 2.0 years (0−6 years). While physician ratings report around 62% of patients in disease remission, 52% with absent and 34% with mild-moderate disease activity, patient-reported disease activity decreased from moderate (PPA 3.0) to low (PPA 2.0) during the observation period. A decrease was observed regarding disease activity parameters, in particular in patients without prior CAN therapy (Table 1, Figure 1). A total of 11 serious adverse events was reported, of which one case of tonsillectomy was classified as drug-related. Conclusion: Interim data of FMF patients from the RELIANCE study, the longest running real-life CAN registry, confirm efficacy and safety of long-term CAN treatment. References: [1]Ozen S, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016;75:644–651. doi:10.1136/annrheumdis-2015-208690 [2]De Benedetti F, et al. Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N Engl J Med 2018;378:1908–19. Table 1. Baseline characteristics and third interim analysis data of patients with FMF Baseline 6 months 12 months 18 months All patients | patients without prior CAN therapy Number of patients, N 54 11 35 7 27 5 16 3 Number (%*) of patients in disease remission (physician assessment) 18 (48.6) 1 (20.0) 19 (73.1) 3 (75.0) 13 (65.0) 1 (50.0) 8 (61.5) 1 (100.0) Physician Global Assessment, percentage* of absent/mild-moderate/severe rating 43/38/11 0/40/60 65/27/0 50/50/0 55/35/0 0/50/0 46/46/0 0/100/0 Patient assessment of current disease activity; 0–10, median (min; max) 3.0 (0; 10) 7.0 (0; 10) 2.5 (0; 7) 2.0 (0; 5) 2.0 (0; 7) 2.0 (0; 2) 2.0 (0; 6) 0.5 (0; 1) Patient assessment of current fatigue; 0–10, median (min; max) 5.0 (0; 10) 5.0 (0; 9) 3.5 (0; 10) 3.0 (1; 6) 3.0 (0; 10) 0.0 (0; 4) 3.0 (0; 7) 0.5 (0; 1) Number (%*) of patients without impairment of social life by the disease 19 (46.3) 3 (37.5) 18 (66.7) 3 (75.0) 14 (66.7) 4 (80.0) 5 (55.6) 2 (66.7) CRP, median (mg/dl) 0.2 1.1 0.2 0.1 0.2 0.0 0.1 0.5 SAA, median (mg/dl) 0.7 6.8 0.8 0.4 0.8 0.6 0.6 0.7 ESR, median (mm/h) 9.0 18.5 6.0 5.0 5.5 4.0 8.0 5.0 SAE Number of events Incidence rate per 100 patient years Total 11 16.23 Arthritis 5 7.38 SARS-CoV-2 infection 2 2.95 Familial Mediterranean Fever 1 1.48 Intestinal Hemorrhage 1 1.48 Pyrexia 1 1.48 Tonsillectomy (SADR) 1 1.48 *not reported for all patients CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reaction; SAE, serious adverse event Disclosure of Interests: Jörg Henes Consultant of: Novartis, AbbVie, Sobi, Roche, Janssen, Boehringer-Ingelheim, Grant/research support from: Novartis, Roche, J. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Frank Dressler Consultant of: Abbvie, Mylan, Novartis, Pfizer, Grant/research support from: Novartis, Frank Weller-Heinemann: None declared, Birgit Kortus-Goetze Consultant of: Novartis, Ivan Foeldvari Consultant of: Novartis, Gerd Horneff Speakers bureau: bbVie, Bayer, Chugai, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Markus Hufnagel Grant/research support from: Novartis, Florian Meier Speakers bureau: Novartis, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi