Background Autoinflammatory periodic diseases (AID) can be treated with the interleukin-1β inhibitor canakinumab (CAN). CAN has been shown to be safe and effective in controlled trials and routine clinical practice. Objectives In this study general safety parameters in patients with canakinumab in cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), hyper-IgD syndrome/mevalonate kinase deficiency (HIDS/MKD) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS) on CAN therapy were investigated in routine clinical practice. Methods RELIANCE is a prospective, non-interventional, observational study in Germany enrolling pediatric (age ≥2 years) and adult patients with a clinically confirmed diagnosis of AID who routinely receive CAN. Efficacy and safety parameters are recorded at baseline and assessed at 6-month intervals. Results Data from N=232 patients (N=229 with baseline visit yet documented) diagnosed with autoinflammatory diseases enrolled in the RELIANCE registry between October 2017 and December 2022 were included in the present interim analysis. Median age of the total study cohort was 20.0 years (2−80 years), 52% were female and median duration of CAN treatment before study entry was 2 years (0−15 years). During the study, 898 adverse events (AE) occurred in N=164 patients (71%). Among the most common AE classified as suspected adverse drug reactions (ADR) were decreased neutrophil count (8 events, IR 1.46), increased inflammatory markers (12 events, IR 2.19), nasopharyngitis (14 events, IR 2.55), and pyrexia (17 events, IR 3.10). In N=35 patients (15%), a total of 98 serious adverse events (SAE) were reported. Of these events, 31 SAE were classified as suspected adverse drug reactions (SADR; Table 1). During the last 3 years of observation within the study, incidence rates (IR) decreased from 76.21 to 51.44 (ADR) and 7.44 to 5.66 (SADR). Patients receiving greater than standard dose CAN experienced higher levels of ADR/SADR compared to patients under less than standard and standard dosing. How much high dosage or severeness of disease contribute to this phenomenon remains unclear. AE related dose reductions have not been reported. Conclusion The 48-month interim data of the RELIANCE study confirm sustained safety of long-term treatment with CAN in the entire study population. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests J. 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, Prasad Oommen Grant/research support from: Novartis, Anne Pankow: None declared, Tilmann Kallinich Speakers bureau: Roche, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Catharina Schuetz 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, Ivan Foeldvari Consultant of: 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, Frank Weller-Heinemann: None declared, Ales Janda: None declared, Markus Hufnagel Grant/research support from: Novartis, Florian Meier Speakers bureau: Novartis, Frank Dressler Consultant of: Abbvie, Mylan, Novartis, Pfizer, Grant/research support from: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, 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, Peter Wasiliew Grant/research support from: Novartis, Michael Fiene: None declared, Daniel Windschall: 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.

Background CAPS (Cryopyrin-associated periodic fever syndromes) are monogenic autoinflammatory diseases causing great burden to patients due to severe systemic and organ inflammation caused by increased production of interleukin-1β (IL-1β). In clinical trials as well as in real-life, the monoclonal antibody canakinumab (CAN) effectively inhibits IL-1β and results in rapid suppression of CAPS symptoms. Objectives The RELIANCE registry explores long-term safety and effectiveness of CAN under routine clinical practice conditions in pediatric (≥2 years) and adult patients with CAPS, including Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS) and neonatal onset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome (CINCA). Methods This prospective, non-interventional, observational study enrolls patients with clinically confirmed diagnoses of CAPS routinely receiving CAN. Clinical data, physician assessments and patient-reported outcomes are evaluated in 6-monthly intervals. Results 107 CAPS patients (53% female; 16% NOMID/CINCA subtypes) were enrolled by December 2022. At baseline, median age was 23 years and median duration of prior CAN treatment was 6 years. 92% of patients received greater than standard dose CAN.75% of the patients were in disease remission at month 48 by physician assessment. Patients report stable low level disease activity (median 2.0 at baseline and 1.5 at month 48) and fatigue (median 3.0 at baseline and 1.0 at month 48). No relevant differences regarding subtype severity were observed (Table 1). At baseline vs. month 48, 46% vs. 50% of patients experienced impairment of social life and 32% vs. 25% reported days off from school or work due to the disease.Severe adverse events (SAE) suspected to be drug-related were reported for N=9 (8.4%) CAPS patients. The incidence rate (IR) per 100 patient-years kept stable over time. Conclusion The 48-month interim analysis of the RELIANCE registry demonstrates that long-term CAN treatment is safe and effective in patients with CAPS, independent of subtype severity. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests J. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Birgit Kortus-Goetze Consultant of: Novartis, Catharina Schuetz Grant/research support from: Novartis, Prasad Oommen Grant/research support from: Novartis, Ales Janda: None declared, 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, Frank Weller-Heinemann: None declared, Tilmann Kallinich Speakers bureau: Roche, Anne Pankow: 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, Ivan Foeldvari Consultant of: Novartis, Peter Wasiliew Grant/research support from: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Michael Fiene: None declared, Florian Meier Speakers bureau: Novartis, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, 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, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi.Table 1Assessment of clinical CAPS disease activity and laboratory markers over time.Baseline24 months48 monthsNOMID/CINCAMWS, FCASNOMID/ CINCAMWS, FCASNOMID/ CINCAMWS, FCASNumber* of patients, N17801054313Number (%**) of patients with days absent from work/school during last 6 months6 (35)25 (32)2 (20)20 (37)0 (0)4 (31)Number (%**) of patients in disease remission (physician assessment)13 (77)53 (68)8 (80)33 (61)2 (67)10 (77)Patient's assessment of current disease activity; 0–10, median (min; max)1.0 (0; 7)2.0 (0; 7)2.0 (0; 4)1.0 (0; 8)0.0 (0; 0)2.0 (0; 5)Patient's assessment of current fatigue; 0–10, median (min; max)3.0 (0; 9)3.0 (0; 9)2.0 (0; 7)2.0 (0; 9)0.0 (0; 0)1.0 (0; 7)Number (%**) of patients without impairment of social life by the disease5 (56)29 (57)3 (50)25 (63)0 (0)2 (67)Current influence of the disease on mood; % of patients** with negative | positive | no influence30 | 10 | 6023 | 19 | 5917 | 33 | 5024 | 37 | 400 | 0 | 025 | 25 | 50CRP, median (mg/dl)0.20.10.30.20.90.1SAA, median (mg/dl)0.40.40.90.40.60.2ESR, median (mm/h)6.05.08.05.05.02.5SAENumber of eventsIR‡ per 100 patient-yearsAll types of SAE6522.85SADR28#9.84NOMID/CINCA00MWS/FACS2611.55# 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 discolouration, tonsillectomy, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (all N=1 event), pyrexia (N=3 events)*subtype not reported for all patients.**not reported for all patients.‡IR = number of events * 36525/ sum of observation days (=103905)CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; SAA, serum amyloid A; SADR, serious adverse drug reaction

Background Familial 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). Objectives The 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. Methods RELIANCE 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. Results This 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. Conclusion Interim data from the RELIANCE study, the longest running real-life CAN registry confirm efficacy and safety of long-term CAN treatment in FMF patients. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Jörg 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.Table 1Assessment 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 patients without impairment 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 reaction

Background The cryopyrin-associated periodic fever syndromes (CAPS) are hereditary monogenic autoinflammatory diseases with severe systemic and organ inflammation due to increased production of Interleukin-1β (IL-1β). The subcutaneously administered monoclonal antibody canakinumab (CAN) effectively inhibits IL-1β and results in rapid remission of CAPS symptoms in clinical trials as well as in real-life. Objectives The RELIANCE registry is designed to explore long-term safety and effectiveness of CAN under routine clinical practice conditions in pediatric (≥2 years) and adult patients with CAPS, including Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal onset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome (CINCA). Methods This prospective, non-interventional, observational study with a 3-year follow-up enrolls patients in Germany with clinically confirmed diagnoses of CAPS routinely receiving CAN. In 6-monthly visits, clinical data, physician assessments and patient-reported outcomes are evaluated starting at baseline. Results 98 CAPS patients (52% female; 15 [15%] NOMID/CINCA subtypes) were enrolled by December 2021 (Table 1). At baseline, median age was 20 years and median duration of prior CAN treatment was 6 years. At the 36 months visit, 74% of patients reached disease remission by physicians´ assessment along with increasing rates of absent disease activity (patient’s assessment, median 2.0 at baseline and 0.0 month 36). In addition, patients reported low levels of fatigue (absent to mild/moderate: 87% at baseline and 95% at month 36). At baseline, CAPS impaired social life in 47% of patients (37% at month 36) and 33% (23% at month 36) reported days off from school/work. Lab parameters were within normal limits. Remission and disease control were sustained as evaluated parameters remained stable or even decreased over time. Table 1. Patient and physician assessment of clinical CAPS disease activity and laboratory markers over time. Baseline 12 months 36 months Number of patients, N 98 72 40 Number (%) of patients in disease remission (physician assessment) 64 (68) 48 (70) 28 (74) Patient’s assessment of current disease activity; 0–10, median (min; max) 2.0 (0; 7) 2.0 (0; 7) 0.0 (0; 6) Patient’s assessment of current fatigue; 0–10, median (min; max) 3.0 (0; 9) 2.0 (0; 8) 1.0 (0; 8) Number (%) of patients without impairment of social life by the disease 34 (53) 35 (65.0) 17 (63) CRP (mg/dl) | SAA (mg/dl); median 0.1 | 0.3 0.1 | 0.5 0.1 | 0.3 Number (%) of patients with disease-related symptoms prior to inclusion into the study | at baseline 12 months 36 months Fever 75 (80) | 14 (15) 19 (28) 4 (11) Fatigue 84 (89) | 49 (52) 36 (52) 17 (46) Conjunctivitis/Uveitis 63 (67) | 27 (29) 21 (30) 7 (19) Headache 68 (72) | 30 (32) 30 (43) 9 (24) Arthralgia/arthritis 80 (85) | 32 (34) 30 (43) 14 (38) Impairment of hearing 35 (37) | 23 (25) 18 (26) 11 (30) Trigger (cold, stress, infections, vaccinations, hormones) 71 (76) | 32 (34) 21 (30) 3 (8) SAE Number of events Incidence rate * per 100 patient years All types of SAE | SADR 63 | 28# 25.98 | 11.55 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 *Incidence rate = number of events * 36,525 / sum of observation days (=88,558) #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, tonsillectomy, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (all N=1 event), pyrexia (3 events) Conclusion The 36-month interim analysis of the RELIANCE study demonstrates that long-term CAN treatment is safe and effective in patients with CAPS, independent of subtype severity. Disclosure of Interests J. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Birgit Kortus-Goetze Paid instructor for: Novartis, Prasad Oommen Grant/research support from: Novartis, Ales Janda: None declared, 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, Catharina Schuetz: None declared, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, 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, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Florian Meier Speakers bureau: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, 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

Background Autoinflammatory diseases (also referred to as hereditary periodic fever syndromes) are caused by defects in the innate immune system. Many autoinflammatory syndromes arise from inherited genetic mutations which begin in childhood and persist throughout adult life. These diseases are often present in several members and generations within a family. Newer research also reflects that, cases can often present at any age through-out childhood, teenage years, and even into older adulthood. These cases appear to be acquired, perhaps due to the interplay of genetic, immune, and environmental factors (somaticism). It is not uncommon that a patient is diagnosed with rheumatoid arthritis, multiple sclerosis or another autoimmune issue, as many physicians are not aware of monogenic inborn errors, nor how to conduct a thorough work up due to a lack of medical knowledge. Objectives Unfortunately, the knowledge base that many doctors have with regards to autoinflammatory genetic diseases is minimal to non-existent, when compared to the well-established expertise of autoimmune disease management. Concerns about the increasing patient accounts detailing lack of medical diagnosis, treatment, and pain management, lead to the important decision to collect further data from the autoinflammatory patient community. The aim of the survey responses collected, and post data aggregation will help identity patient trends and use this information to educate and increase awareness amongst the medical community as to the unmet diagnostic and treatment requirements for the autoinflammatory population. Methods A questionnaire comprised of thirty questions was developed by members of the patient organization FMF & AID Global Association (Executive Director, Malena Vetterli with Research Director, H. Ellen Cohen) under the guidance of Dr. med. Juergen Rech focused on collecting basic information (e.g. age, country, onset and duration of symptoms, pain and fatigue). The survey was published at the end of 2020 on social media (Facebook) and on the FMF&AID website ( www.fmfandaid.org ). Participation was voluntary and the patients agreed that the anonymised response information of the survey may be evaluated and published. This international survey was approved by the ETHICS Committee FAU in Erlangen-Nuremberg, Germany. Results Worldwide, over a thousand patients or parents/caregivers of patients (younger than 18 years) in fifty-two countries took part in this survey and answered the questionnaire. Eighty percent (80%) of the participants had already been diagnosed with an autoinflammatory disease. However, despite classic periodic symptom presentation, twenty percent (20%) of the participants were still without a concise diagnosis. FMF - forty-three percent (43%) was cited as the most common diagnosis and M. Behçet thirty percent (30%) as the second, with a variety of others (e.g. PFAPA, CAPS, HIDS, TRAPS, DADA, Yao syndrome, and uSAID). The minimum age at diagnosis ranged from 1 to 70+ years old with an average age of 33 years when properly diagnosed. Three-hundred and nine (309) patients reported that their pain had not been taken seriously and adequately treated in the past. Pain and fatigue, as measured by the standard visual analogue scale (VAS 0-10), was high in the past 30 and 7 days, respectively. VAS pain 30 days was 4.8 (SD +/-2.7) or 7 days with 4.2 (SD +/- 3), as well as fatigue VAS 30 days 5.7 (SD +/- 2.8) or fatigue VAS 7 days with 5.5 (SD +/- 3). Conclusion One-fifth of patients with classic symptoms of autoinflammatory diseases remain undiagnosed and therefore not specifically treated. Although, the rest of the participants eighty percent (80%) have a diagnosis of an autoinflammatory disease, therapy does not appear to be sufficient to manage their wide-ranging and debilitating symptoms, in particular pain and fatigue. Patients continue to carry the burden of receiving mental diagnosis vs actual medical diagnosis and are still forced to seek additional medical support, often incurring travel or relocation costs to obtain proper care. Disclosure of Interests Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Biogen, BMS, Chugai, GSK, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Koray Tascilar: None declared, Abdurrahman Tufan: None declared, Marco Gattorno: None declared, J. B. Kuemmerle-Deschner: None declared, Seza Ozen: None declared, Tobias Krickau: None declared, Ellen Cohen: None declared, Leonardo Oliveira Mendonca: None declared, Apostolos Kontzias: None declared, Malena Vetterli: None declared

Background Autoinflammatory 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. Objectives The 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). Methods RELIANCE 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. Results Here, 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 event Number of events IR ‡ AE total 653 154.43 AE non-serious 563 133.15 AE, non-serious, not related 317 74.97 AE, URI 16 3.78 AE, non-serious adverse drug reaction 246 58.18 SAE, total 90 21.28 SAE, not related 60 14.19 SADR # , total 30 7.09 # 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 reaction Incidence rate = number of events * 36,525 / sum of observation days (=154,442) Conclusion The 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 Interests J. 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