OP0092 LONG-TERM SAFETY AND EFFECTIVENESS OF CANAKINUMAB IN CRYOPYRIN-ASSOCIATED PERIODIC SYNDROMES (CAPS) – 30-MONTH DATA FROM THE RELIANCE REGISTRY
Authors: J. B. Kuemmerle-Deschner, B. Kortus-Goetze, P. Oommen, A. Janda, J. Rech, T. Kallinich, F. Weller-Heinemann, G. Horneff, I. Foeldvari, C. Schuetz, M. Borte, A. Braner, J. Weber-Arden, N. Blank
Journal: Annals of the Rheumatic Diseases (2021)

Background: 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 &amp; Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp &amp; 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