Pos0220 long-term safety and effectiveness of canakinumab in cryopyrin-associated periodic syndromes – 36-month data from the reliance registry

BackgroundThe 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.ObjectivesThe 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).MethodsThis 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.Results98 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.Baseline12 months36 monthsNumber of patients, N987240Number (%) 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 disease34 (53)35 (65.0)17 (63)CRP (mg/dl) | SAA (mg/dl); median0.1 | 0.30.1 | 0.50.1 | 0.3Number (%) of patients with disease-related symptomsprior to inclusion into the study | at baseline12 months36 monthsFever75 (80) | 14 (15)19 (28)4 (11)Fatigue84 (89) | 49 (52)36 (52)17 (46)Conjunctivitis/Uveitis63 (67) | 27 (29)21 (30)7 (19)Headache68 (72) | 30 (32)30 (43)9 (24)Arthralgia/arthritis80 (85) | 32 (34)30 (43)14 (38)Impairment of hearing35 (37) | 23 (25)18 (26)11 (30)Trigger (cold, stress, infections, vaccinations, hormones)71 (76) | 32 (34)21 (30)3 (8)SAENumber of eventsIncidence rate* per 100 patient yearsAll types of SAE | SADR63 | 28#25.98 | 11.55CRP, 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)ConclusionThe 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 InterestsJ. 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