BackgroundFamilial Mediterranean Fever (FMF) is a chronic disease characterized by recurrent attacks of fever as well as serositis and bears the risk of serious complications (e. g. amyloidosis). Treatment of FMF according to EULAR aims to control acute attacks and subclinical inflammation as well as to improve patient´s quality of life1. Clinical data indicate that the inhibition of interleukin-1β with canakinumab (CAN) is effective in controlling and preventing flares in FMF patients2.ObjectivesThe present study explores the long-term efficacy and safety of canakinumab in routine clinical practice conditions in pediatric (age ≥2 years) and adult FMF patients.MethodsRELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a 3-year follow-up period. Patients with clinically confirmed FMF diagnosis who routinely receive canakinumab are enrolled in order to evaluate effectiveness and safety of canakinumab. 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 assessed at 6-monthly intervals within the 3-year observation period of the study.ResultsThis interim analysis of FMF patients (N=74) enrolled by December 2021 includes baseline as well as 6- to 24-month data. Mean age in this cohort was 25 years (2−61 years) and the proportion of female patients was 51 % (N=38). At baseline, median duration of prior CAN treatment was 1.0 years (0−6 years).At month 24, physician ratings report around 63% of patients in disease remission and patient-reported disease activity (mean PPA) decreased from moderate (3.0) to low (2.6) during the observation period. Other disease activity parameters also decreased (Table 1). A total of 18 serious adverse events were reported, of which 2 (1 case of tonsillectomy and 1 case of tachycardia) were classified as drug - related.Table 1.Baseline characteristics and 4th interim analysis data of patients with FMFBaseline12 months24 monthsNumber of patients, N744624Number (%) of patients with days absent from work/school during last 6 months6 (8)11 (24)9 (38)Number (%) of patients in disease remission (physician assessment)22 (45)23 (72)12 (63)Patient’s assessment of current disease activity; 0–10, median (min; max)2.0 (0; 10)2.0 (0; 7)2.0 (0; 10)Patient’s assessment of current fatigue; 0–10, median (min; max)5.0 (0; 10)2.0 (0; 10)4.0 (0; 10)Number (%) of patients without impairment of social life by the disease27 (50)28 (80)8 (67)CRP (mg/dl) | SAA (mg/dl) | ESR (mm/h); median0.2 | 0.7 | 8.00.2 | 0.5 | 4.00.2 | 0.7 | 6.0Number (%) of patients with disease-related symptomsprior to inclusion into the study | at baseline12 months24 monthsFever68 (93) | 14 (29)8 (25)3 (16)Abdominal pain67 (92) | 20 (41)10 (31)4 (21)Thoracic pain45 (62) | 5 (10)3 (9)1 (5)Headache34 (47) | 11 (22)7 (22)5 (26)Myalgia23 (32) | 6 (12)4 (13)2 (11)Arthralgia/arthritis39 (54) | 16 (33)9 (28)5 (26)Dermal symptoms (urticarial, maculopapulose)15 (21) | 5 (10)3 (9)0 (0)SAENumber of eventsIncidence rate# per 100 patient yearsAll types of SAE1814.03SADR21.56Incidence rate = number of events * 36,525 / sum of observation days (=46,848).CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reaction; SAE, serious adverse events.ConclusionInterim data of FMF patients from the RELIANCE study, the longest running real-life canakinumab registry confirm efficacy and safety of long-term canakinumab 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.Disclosure of InterestsJörg 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, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, 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, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Florian Meier Speakers bureau: Novartis, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Frank Weller-Heinemann: None declared, Birgit Kortus-Goetze Consultant of: Novartis, Markus Hufnagel Grant/research support from: Novartis, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Prasad Oommen Grant/research support from: 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.

BackgroundAutoinflammatory diseases (AID) are characterized by severe systemic and organ inflammation as well as high burden of disease for patients and their families. Treatment with the monoclonal antibody canakinumab (CAN), an interleukin-1β inhibitor, has been proven to be safe and effective in clinical trials and real-life.ObjectivesThe present study explores the long-term efficacy and safety of CAN in routine clinical practice conditions in pediatric (age ≥2 years) 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).MethodsRELIANCE is a prospective, non-interventional, observational study based in Germany. Patients with clinically confirmed diagnoses of AID routinely receiving CAN are enrolled. Besides efficacy parameters regarding disease activity and remission, safety parameters were recorded at baseline and assessed at 6-monthly intervals.ResultsHere, we present the interim analysis of patients with AID (N=199) enrolled in the RELIANCE Registry between October 2017 and December 2021. Mean age in this cohort was 24.4 years (2–79 years) and the proportion of female patients was 53% (N=104). At baseline, median duration of prior CAN treatment was 2 years (0–12 years).A total of 123 patients (62%) experienced any AE (N=653) among which nasopharyngitis, increase of inflammatory markers and pyrexia were the most frequent AE with incidence rates per 100 patient years (IR) of 8.3, 6.2, and 6.2, respectively.29 patients (15%) were affected by severe AE (SAE, total number N=90) including 11 patients (6%) with SAE suspected to be drug-related (SADR; total number N=30) with IR from 0.2 to 0.7 (Table 1). Overall, 16 AE comprised upper respiratory tract infections (URI). One death (COVID-19, not related) and one malignancy (skin papilloma, not related) were reported. No vertigo and no hypersensitivity reactions were observed. N=10 (IR 2.36) vaccination reactions were reported (no SAE).Table 1.Overview of the CAN safety data of the RELIANCE study across all study indications (N=199 patients).Type of eventNumber of eventsIR‡AE total653154.43AE non-serious563133.15AE, non-serious, not related31774.97AE, URI163.78AE, non-serious adverse drug reaction24658.18SAE, total9021.28SAE, not related6014.19SADR#, total307.09#Abdominal pain; Alport’s syndrome, appendicitis, arthralgia, blister, cardiovascular disorder, chest pain, circulatory collapse, dehydration, diplopia, dyspnoea, erythema, febrile convulsion, gastroenteritis, glomerulonephritis, Haemophilus test positive, myalgia, oedema, pneumonia, premature delivery, skin discoloration, tachycardia, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (each n=1 event, IR 0.24‡), tonsillectomy (2 events, IR 0.47‡), pyrexia (3 events, IR 0.71‡), not yet coded (hospital admission due to exsiccosis upon gastroenteritis, 1 event, IR 0.35‡)‡IR, incidence rate per 100 patient years; AE, adverse event; URI, upper respiratory tract infection; SAE, severe adverse event, SADR, severe adverse drug reactionIncidence rate = number of events * 36,525 / sum of observation days (=154,442)ConclusionThe interim data from the RELIANCE study, the longest running real-life canakinumab registry, confirm safety of long-term canakinumab treatment across the entire study population. A trend for dose-related increase of SAE/SADR requires continuous close monitoring and awareness in patient groups (children, severe phenotypes, certain genotypes) requiring greater than standard dose treatment regimens.Disclosure of InterestsJ. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Jörg Henes Consultant of: Novartis, AbbVie, Sobi, Roche, Janssen, Boehringer-Ingelheim, Grant/research support from: Novartis, Roche, Birgit Kortus-Goetze Consultant of: Novartis, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Prasad Oommen Grant/research support from: Novartis, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Frank Weller-Heinemann: None declared, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ales Janda: None declared, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Catharina Schuetz: None declared, Frank Dressler Consultant of: Abbvie, Mylan, Novartis, Pfizer, Grant/research support from: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Markus Hufnagel Consultant of: Novartis and SOBI, Florian Meier Speakers bureau: Novartis, Michael Fiene: None declared, 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

BackgroundFamilial Mediterranean Fever (FMF) is characterized by recurrent attacks of fever, serositis, and elevated laboratory parameters (CRP, SAA). According to EULAR recommendations, treatment goals are the control of acute attacks and subclinical inflammation as well as the improvement of patient´s quality of life. In a phase 3 pivotal study (CLUSTER study), FMF patients have been successfully treated with the interleukin-1β inhibitor canakinumab (CAN).ObjectivesThe RELIANCE registry explores the long-term efficacy and safety of CAN under routine clinical practice conditions in pediatric (age ≥2 years) and adult patients with FMF and other recurrent hereditary fever conditions.MethodsRELIANCE is a prospective, non-interventional, observational study that enrolls patients with clinically confirmed diagnoses of FMF routinely receiving CAN. Clinical data, physician assessments and patient-reported outcomes are assessed at baseline and 6-monthly intervals.ResultsThis interim analysis includes baseline as well as 18- and 36-month data from N=96 FMF patients (CAN-pretreated: N=71, CAN-naïve: N=20) enrolled by December 2022. Median age in this cohort was 21.5 years (2−61 years) and the proportion of female patients was 46%. At baseline, median duration of prior CAN treatment was 1.0 years (0−6 years).The MEFV genotype has been documented in 67 patients. Among 53 (79%) carriers of pathologic MEFV variants, 17 were homozygous, 6 heterozygous plus a second pathologic variant, 8 heterozygous plus a non-pathologic variant, and 22 heterozygous plus wild type.At month 36, disease activity was mild (3 and 2 out of 10) according to patients rating and lab parameters. Physician assessment indicated disease remission in 60% of the patients (53% at baseline) and 57%/14% of the patients having no/mild-moderate disease activity. The majority of patients reported no impairment of social life (100%, 75%) nor negative impact on mood (88%, 100%) due to the disease. Disease activity parameters decreased in the observation period, particularly in patients without prior CAN therapy (Table 1). In total, 22 serious adverse events (SAE) were reported, of which 3 were classified as drug related.ConclusionInterim data from the RELIANCE study, the longest running real-life CAN registry confirm efficacy and safety of long-term CAN treatment in FMF patients.Table 1.Assessment of clinical disease activity and laboratory markers in CAN pretreated and CAN naïve FMF patients.Baseline18 months36 monthsCAN pretreated patients vs. patients CAN naïve at baselineCAN pre- treatedCAN naïveCAN pre- treatedCAN naïveCAN pre- treatedCAN naïveNumber* of patients, N71203411195Number (%**) of patients with days off work/school during the last 6 months8 (11)2 (10)9 (27)1 (9)5 (26)0 (0)Number (%**) of patients in disease remission (physician assessment)32 (59)2 (20.0)16 (64)3 (60.0)10 (63)2 (50.0)Patient’s assessment of current disease activity; 0–10, median (min; max)2.0 (0; 10)7.0 (0; 10)2.0 (0; 6)0.0 (0; 7)3.0 (1; 8)2.0 (0; 4)Patient’s assessment of current fatigue; 0–10, median (min; max)4.0 (0; 10)5.5 (0; 9)3.0 (0; 9)2.0 (0; 7)3.5 (0; 9)2.0 (0; 6)Number (%**) of patientswithoutimpairment of social life by the disease28 (56)9 (60)17 (85)7 (88)8 (100)3 (75)Current influence of the disease on mood; %** of patients with negative | positive | no influence18 | 10 | 7119 | 0 | 815 | 14 | 8113 | 0 | 8813 | 13 | 750 | 25 | 75CRP, median (mg/dl)0.10.50.10.20.20.0SAA, median (mg/dl)0.63.30.61.00.70.6ESR, median (mm/h)5.09.07.05.05.07.0SAENumber of eventsIncidence rate‡per 100 patient-yearsAll types of SAE2211.64SADR3#1.59CAN-pretreated patients32.19CAN-naïve patients00.00#Tachycardia, tonsillitis, and one further SAE (not yet coded), each N=1*CAN status not reported for all patients*not reported for all patients‡Incidence rate = number of events * 36525/ sum of observation days (=69050)CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reactionREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsJörg Henes Consultant of: Novartis, AbbVie, Sobi, Roche, Janssen, Boehringer-Ingelheim, Grant/research support from: Novartis, Roche, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Anne Pankow: None declared, Ivan Foeldvari Consultant of: Novartis, Frank Dressler Consultant of: Abbvie, Mylan, Novartis, Pfizer, Grant/research support from: Novartis, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Tilmann Kallinich Speakers bureau: Roche, Prasad Oommen Grant/research support from: Novartis, Florian Meier Speakers bureau: Novartis, Frank Weller-Heinemann: None declared, Birgit Kortus-Goetze Consultant of: Novartis, Markus Hufnagel Grant/research support from: Novartis, Jürgen Rech Speakers bureau: AbbVie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: AbbVie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Ioana Andreica Speakers bureau: Abbvie, Chugai, Novartis, UCB, MSD, Lilly, Sobi, Astrazeneca, Amgen, Pfizer, Gilead, Paid instructor for: Astrazeneca, UCB; Consultant Abbvie, Chugai, Novartis, UCB, Galapagos, Takeda, Astrazeneca, Lilly, Boehringer Ingelheim, Amgen, Sobi, Julia Weber-Arden Employee of: Novartis, J. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi.