Abstract: 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

Abstract: Although children and adolescents are less likely to develop COVID-19 and generally show milder disease courses, it is unclear what impact the SARS-CoV2 infection has on children and adolescents with rheumatic and musculoskeletal disease (RMD). Due to their underlying disease as well as therapeutic immunosuppression these patients may be at higher risk of being more severely affected by SARS-CoV2. Furthermore, SARS-CoV2 infection might trigger a flare of the underlying disease. Objectives: To evaluate clinical characteristics and disease course of COVID-19 in children and adolescents with RMD and to analyze possible effects of SARS-CoV2 infection on the underlying disease under different therapeutic regimens. Methods: Data from juvenile patients with RMD recorded via the SARS-CoV2 questionnaire within the National Pediatric Rheumatology Database and the registry for hospitalized children and adolescents with COVID-19 of the German Society for Pediatric Infectious Diseases were analyzed. In addition to age, sex and diagnosis, information was collected about the date and method of a positive SARS-CoV2 testing, reason for testing, on clinical manifestations, disease course, treatment and outcome of COVID-19, on drug therapy at the time of virus detection, on disease activity (NRS 0 – 10, 0 = best) of the underlying disease at the last visit before and after the SARS-CoV2 infection. Results: From April 17 th 2020 until January 25 th 2021, data of 67 patients with RMD and confirmed SARS-CoV2 infection were collected. Mean age was 13.5 ± 3.9 years with equal sex distribution. The majority of patients were diagnosed with juvenile idiopathic arthritis (JIA, 64%), 12 (18%) patients had an autoinflammatory disease (FMF, CAPS, PFAPA, TRAPS) and 5 (7%) a connective tissue disease. Fifty-two patients (78%) were treated with a disease modifying antirheumatic drug (DMARD), 39% with a biological DMARD and 9% systemic glucocorticoids at the time of SARS-CoV-2 infection. Nineteen patients (28%) were tested for SARS-CoV-2 because of typical symptoms, the majority (67%) because of contact to an infected person. PCR was used most often (in 60 %). 52 patients (78%) developed symptoms of COVID-19, 15 patients remained asymptomatic. The most common symptom of COVID-19 was rhinitis (42%) and fever (38%), followed by fatigue (34%), taste/smell disorder (33%), sore throat (27%) and cough (23%). Disease severity was graded as mild in 44 of 52 (85%) symptomatic patients, only two patients were hospitalized, one of whom required intensive care and died of cardiorespiratory failure 3 days after symptom onset. In 22 of 26 (85%) SARS-CoV2-positive patients, no relevant increase in disease activity (difference in NRS ≤ 1 before/after infection) of the underlying disease was observed 31 days after symptom onset (median, IQR 17-52 days). One patient, who had paused tocilizumab for 2 doses, experienced a flare of his seronegative polyarthritis 2 months after asymptomatic SARS-CoV-2 infection. Conclusion: In our cohort, the clinical picture of COVID-19 in children and adolescents with RMD was similar to that of healthy peers. The majority of patients showed mild disease course with good outcome under various medications, however, one patient with a severe course of COVID-19 died. In addition, SARS-CoV2 infection does not appear to have a relevant impact on the underlying disease activity, whereas discontinuation of therapy might pose a risk of flare. Disclosure of Interests: None declared.

Abstract: Familial 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 life 1 . Clinical data indicate that the inhibition of interleukin-1β with canakinumab (CAN) is effective in controlling and preventing flares in FMF patients 2 . Objectives The 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. Methods RELIANCE 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. Results This 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 4 th interim analysis data of patients with FMF Baseline 12 months 24 months Number of patients, N 74 46 24 Number (%) of patients with days absent from work/school during last 6 months 6 (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 disease 27 (50) 28 (80) 8 (67) CRP (mg/dl) | SAA (mg/dl) | ESR (mm/h); median 0.2 | 0.7 | 8.0 0.2 | 0.5 | 4.0 0.2 | 0.7 | 6.0 Number (%) of patients with disease-related symptoms prior to inclusion into the study | at baseline 12 months 24 months Fever 68 (93) | 14 (29) 8 (25) 3 (16) Abdominal pain 67 (92) | 20 (41) 10 (31) 4 (21) Thoracic pain 45 (62) | 5 (10) 3 (9) 1 (5) Headache 34 (47) | 11 (22) 7 (22) 5 (26) Myalgia 23 (32) | 6 (12) 4 (13) 2 (11) Arthralgia/arthritis 39 (54) | 16 (33) 9 (28) 5 (26) Dermal symptoms (urticarial, maculopapulose) 15 (21) | 5 (10) 3 (9) 0 (0) SAE Number of events Incidence rate # per 100 patient years All types of SAE 18 14.03 SADR 2 1.56 Incidence 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. Conclusion Interim 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 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, 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.

Abstract: 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

Abstract: In clinical trials as well as in real-life, the IL-1ß inhibitor canakinumab leads to rapid remission of symptoms in the treatment of CAPS, a monogenic autoinflammatory disease with severe systemic and organ inflammation. Objectives: The RELIANCE registry is designed to explore long-term safety and effectiveness of canakinumab 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 with clinically confirmed diagnoses of CAPS routinely receiving canakinumab. In 6-monthly visits, clinical data, physician assessments and patient-reported outcomes are evaluated starting at baseline with last update at 30 months of follow-up in the total cohort including the cohort with severe CAPS subtypes (NOMID/CINCA). Results: 91 CAPS patients (50% female; 14 [15%] NOMID/CINCA subtypes) were enrolled by December 2020 (Table 1). At baseline, median age was 20.5 years and median duration of prior canakinumab treatment was 6 years. 11 drug related severe adverse events per 100 patient years were reported. 68% of patients reached disease remission by physicians´ assessment along with rates of 40-61% absent disease activity in PGA. Patients reported stable low level disease activity, fatigue and Auto-Inflammatory Diseases Activity Index scores (AIDAI, figure 1). CAPS was impairing social life in 50% of patients and another 50% reported days off from school/work. Lab parameters were within normal limits. Table 1. Patient and physician assessment of clinical CAPS disease activity and laboratory markers over time. Baseline 12 months 30 months Total cohort NOMID/ CINCA Total cohort NOMID/ CINCA Total cohort NOMID/ CINCA Number of patients, N 91 14 67 8 28 4 Number (%) of patients with days absent from work/school during last 6 months 30 (34) 4 (29) 28 (42) 2 (25) 17 (61) 4 (100) Number (%) of patients in disease remission (physician assessment) 61 (68.5) 11 (78.6) 42 (66.7) 4 (66.7) 19 (67.9) 4 (100.0) Physician Global Assessment, percentage of absent/mild-moderate/severe rating, % 40 / 53 / 2 57 / 36 / 0 33 / 60 / 2 33 / 50 / 0 61 / 39 / 0 75 / 25 / 0 Patient assessment of current disease activity; 0–10, median (min; max) 2.0 (0; 7) 1.0 (0; 6) 1.0 (0; 7) 1.0 (0; 5) 0.0 (0; 7) 0.0 (0; 4) Patient assessment of current fatigue; 0–10, median (min; max) 3.0 (0; 9) 2.0 (0; 6) 3.0 (0; 8) 2.0 (0; 8) 1.0 (0; 8) 4.0 (0; 5) Number (%) of patients without impairment of social life by the disease 32 (52.5) 4 (50.0) 31 (62.0) 3 (42.9) 11 (47.8) 1 (33.3) CRP, median (mg/dl) 0.1 0.2 0.1 0.5 0.0 0.2 SAA, median (mg/dl) 0.3 0.4 0.5 0.9 0.3 0.1 ESR, median (mm/h) 5.0 6.0 5.0 3.5 5.0 5.5 SAE Number of events Incidence rate per 100 patient years Total cohort NOMID/CINCA Total cohort NOMID/CINCA All types of SAE 39 3 14.72 11.72 SADR 20 # 0 10.69 0.00 # Alport’s syndrome, appendicitis, blister, cardiovascular disorder, chest pain, circulatory collapse, erythema, febrile convulsion, glomerulonephritis, haemophilus test positive, pneumonia, premature delivery, skin discolouration, tonsillectomy, tonsillitis bacterial, tonsillitis streptococcal (all N=1 event), pyrexia (N=3 events), not yet coded (inpatient admission, N=1 event) 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 Conclusion: The 30-month interim analysis of the RELIANCE study demonstrates that long-term canakinumab treatment is safe and effective in patients with any subtype of CAPS. However, impairment of social life and days off school/work still exists. 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, Prasad Oommen Grant/research support from: Novartis, Ales Janda: None declared, Jürgen Rech Speakers bureau: bbvie, 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, 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, Catharina Schuetz: None declared, Michael Borte Grant/research support from: Pfizer, Shire, Axel Braner Consultant of: Novartis and 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

Abstract: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory condition characterized by severe systemic and organ inflammation. In a phase 3 pivotal trial ( CLUSTER study), TRAPS patients have been successfully treated with the interleukin-1β inhibitor canakinumab. 45% of patients reached clinical remission after 16 weeks (primary endpoint) 1 . Canakinumab has been approved and applied for the treatment of TRAPS patients since 2017 2 . Objectives: The present study explores the long-term efficacy and safety of canakinumab under routine clinical practice conditions in pediatric (age ≥2 years) and adult TRAPS patients. Methods: RELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a 3-year follow-up period. Patients with clinically confirmed diagnoses of TRAPS, CAPS, FMF or HIDS/MKD who routinely receive canakinumab are enrolled in order to evaluate efficacy and safety of canakinumab under standard clinical practice conditions. Disease activity and remission by physician assessment, disease activity and fatigue by patient assessment, days absent from school/work due to study indication, inflammatory markers, and AIDAI (Auto-Inflammatory Diseases Activity Index) score were assessed at baseline and at 6-monthly intervals. Results: The interim analysis of TRAPS patients enrolled by December 2020 includes baseline (N=16, including 1 patient with atypical TRAPS) and preliminary 18-month data. Mean age in this cohort was 23 years (3−43 years) and the median duration of prior CAN treatment was 1.0 year (0−4 years). Physician assessment indicated 60-80% remission and laboratory parameters were within normal range. Disease control by patient assessment showed no major changes regarding the analyzed parameters (Table 1, Figure 1). Of the three serious adverse events reported none was classified as drug-related. Conclusion: Preliminary analysis of 18 month interim data of TRAPS patients treated with CAN available from the RELIANCE study indicate stable efficacy and safety of CAN long-term treatment. References: [1]De Benedetti F, et al. Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N Engl J Med 2018;378:1908–19. [2]Ilaris, INN-canakinumab (europa.eu) Table 1. Baseline characteristics and interim analysis data of patients with TRAPS Baseline 6 months 12 months 18 months Number of patients, N 16 13 10 6 Median age, years (min; max) 23 (3; 43) 17 (3; 43) 16 (4; 38) 25 (4; 43) Females (%) 11 (69) 9 (69) 7 (70) 3 (50) Median duration of prior CAN therapy at baseline, years (min; max) 1.0 (0; 4) 1.0 (0; 4) 1.0 (0; 4) 1.5 (0; 2) Number (%) of patients in disease remission (physician assessment) 9 (60.0) 9 (81.8) 7 (77.8) 4 (80.0) Physician Global Assessment, percentage of absent/mild-moderate/severe rating 40 / 53 / 0 82 / 9 / 0 44 / 44 / 11 80 / 20 / 0 Patient assessment of current disease activity; 0–10, median (min; max) 1.5 (0; 5) 1.0 (0; 4) 1.0 (0; 6) 0.0 (0; 3) Patient assessment of current fatigue; 0–10, median (min; max) 2.0 (0; 8) 1.0 (0; 7) 2,5 (0; 8) 4.0 (0; 7) Number (%) of patients without impairment of social life by the disease 4 (50) 5 (63) 2 (33) 3 (60) Number (%) of patients with days absent from work/school during last 6 months 8 (50) 5 (39) 5 (56) 3 (50) CRP, median (mg/dl) 0.1 0.1 0.1 0.0 SAA, median (mg/dl) 0.5 0.4 0.4 0.3 ESR, median (mm/h) 7.0 5.0 5.0 5.0 SAE Number of events Incidence rate per 100 patient years Total 3 14.7 Circulatory collapse (non fatal) 1 4.9 Dizziness 1 4.9 Headache 1 4.9 CRP, c-reactive protein; ESR , erythrocyte sedimentation rate; SAA, serum amyloid A; SAE, serious adverse event Disclosure of Interests: Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi, Jörg Henes Consultant of: Novartis, AbbVie, Sobi, Roche, Janssen, Boehringer-Ingelheim, Grant/research support from: Novartis, Roche, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Prasad Oommen Grant/research support from: Novartis, Catharina Schuetz: None declared, Michael Borte Grant/research support from: Pfizer, Shire, Julia Weber-Arden Employee of: Novartis, J. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi

Abstract: 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 & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & 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

Abstract: The ProKind Commission of the Society for Paediatric and Adolescent Rheumatology (GKJR) has developed evidence- and consensus-based protocols for the diagnosis and therapy of children and adolescents with defined rheumatic diseases (e.g., [1]). In the ProKind-Rheuma project, it is now investigated whether the protocols are followed in everyday clinical practice and what the treatment-associated outcomes are. Objectives To investigate the mode of treatment and treatment response in patients with polyarticular juvenile idiopathic arthritis (pJIA). Methods ProKind-Rheuma is a multicenter prospective non-interventional observational study. Patients with pJIA enrolled until 17/1/2022 were included into this analysis. Treatments and outcomes up to the 3-month follow-up visit (3FU) were analyzed. Disease states were categorized based on the 2021 cJADAS10 cutoffs [2]. Results To date, 18 pediatric rheumatology facilities have participated in ProKind-Rheuma. Data from 203 patients with JIA are available. Of those, 44% have oligoarthritis, 36% polyarthritis, 9% systemic JIA, 6% enthesitis-related arthritis and 3% psoriatic arthritis. In total, 76 patients were diagnosed with pJIA, 38 with already completed 3FU: For 23 patients with pJIA and completed 3FU, we were able to analyze the protocol-defined [1] treatment goal of at least “minimal im provement”. In total, 18 (78%) achieved minimal improvement, 5 (22%) missed it. For 4 of those 5 patients, the underlying MTX therapy was escalated to a bDMARD (3 changed to MTX+bDMARD-combi, 1 to bDMARD-mono). In 3 other patients, therapy was also escalated to an MTX+bDMARD-combi. Between baseline and 3FU, 72% achieved cJADAS10-disease state improvement (Table 1) by at least one category (range 1 - 2), 0% decreased. Table 1. *based on non-missing values At Baseline all At Baseline with 3FU At 3FU Total 76 38 Female, n (%) 58 (76) 30 (79) Age (years), Mdn (IQR) 9 (3-12) 7 (2-12) 7.5 (3-12) Time since diagnosis (months), Mdn (IQR) 0 (0-1) 0 (0-1) 4 (3-4) RF-positivity, n (%) 8 (11) 3 (8) Number of active joints (arthritis), Mdn (IQR) 7 (4-12) 7 (5-12) 2 (0-4) JADAS10 (0-40), Mean (SD) (N BL+3FU = 23) 18.6 (7.4) 19.6 (7.6) 7.2 (4.2) cJADAS10 (0-30), Mean (SD) (N BL+3FU = 29) 16.3 (5.9) 16.7 (6.1) 7.1 (4.1) State of inactive disease (cJADAS10≤2.5), n (%*) 0 (0) 0 (0) 4 (13) State of minimal disease activity (2.5 〈 cJADAS10≤5), n (%*) 1 (2) 1 (3) 9 (28) State of moderate disease activity (5 〈 cJADAS10 ≤16), n (%*) 33 (54) 17 (50) 18 (56) State of high disease activity (cJADAS10 〉 16), n (%*) 27 (44) 16 (47) 1 (3) CHAQ (0-3), Mean (SD) 0.8 (0.8) 0.9 (0.8) 0.3 (0.5) Pain (NRS 0 - 10), Mean (SD) 4.3 (3) 4.7 (3) 2.2 (2.7) PedsQL 4.0 total score, Mean (SD) 66.3 (22.2) 65.4 (21.8) 78.4 (17.6) Intraarticular glucocorticoids 〉 4 joints (ever), n (%) 12 (16) 5 (13) 7 (18) Glucocorticoid pulses (ever), n (%) 22 (29) 12 (32) 13 (34) Methotrexate, n (%) 56 (74) 31 (82) 34 (90) bDMARDs, n (%) 7 (9) 2 (5) 9 (24) Within the first 3 months after diagnosis, the treatment pathways proposed by the ProKind Commission [1] were followed in about three-quarters of patients: i) 5 (13%) received MTX and intra-articular glucocorticoid injections in more than 4 joints (IAGC), but no high-dose intravenous glucocorticoid pulse (HDGC) or bDMARD; ii) 8 (21%) received MTX and HDGC (no bDMARD, no IAGC); iii) 16 (42%) patients received MTX, of whom 4 received a bDMARD up to or at the 3FU (no HDGC, no IAGC). Nine (24%) patients were not treated with MTX or did not fit any of these categories, mostly due to starting bDMARD therapy in conjunction with HDGC or IAGC. Conclusion In the routine care of JIA patients with polyarthritis, the proposed treatment protocol and treat-to-target strategy are followed in most patients. At 3FU, improvements of JADAS10 and other outcomes were evident, with 41% having achieved inactive or minimal active disease. ProKind is funded by the Innovation Fund “Gemeinsamer Bundesausschuss”, FKZ: 01VSF18031 References [1]Horneff et al. Pediatric Rheumatology 2017; 15:78 [2]Trincianti et al. Arthritis Rheumatol. 2021 Nov; 73(11):1966-1975 Acknowledgements We are grateful to all physicians, medical professionals and everyone else who has so far contributed and supported the ProKind-Rheuma project. Moreover, we want to express special gratitude to all patients and their parents for their participation. Disclosure of Interests Sascha Eulert: None declared, Kristina Vollbach: None declared, Klaus Tenbrock: None declared, Jens Klotsche: None declared, Dirk Foell Speakers bureau: Speaker fees/honoraria from Boehringer, Novartis, Werfen and Sobi, Grant/research support from: Novartis and Sobi, Johannes-Peter Haas: None declared, Frank Weller-Heinemann: None declared, Sonja Mrusek: None declared, Prasad Oommen: None declared, Daniel Windschall Speakers bureau: Research support and speakers fee: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Grant/research support from: Research support and speakers fee: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Kirsten Moenkemoeller: None declared, Tilmann Kallinich: None declared, Markus Hufnagel: None declared, Ivan Foeldvari Consultant of: Addvisory board: Hexal, Novartis, Pfizer, Toni Hospach Consultant of: Advisory board: Sobi, Novartis, Moritz Klaas: None declared, Michael Rühlmann: None declared, Ralf Trauzeddel: None declared, Normi Brueck: None declared, Catharina Schütz: None declared, J. B. Kuemmerle-Deschner: None declared, Ariane Klein: None declared, Kirsten Minden Speakers bureau: Speaker: Pfizer, Novartis, Gerd Horneff: None declared