OP0163 LONG-TERM EFFECTIVENESS OF CANAKINUMAB IN PATIENTS WITH CRYOPYRIN-ASSOCIATED PERIODIC SYNDROME
Authors: J. B. Kuemmerle-Deschner, Norbert Blank, Michael Borte, Ivan Foeldvari, Gerd Horneff, Prasad Oommen, Catharina Schuetz, Frank Weller-Heinemann, Julia Weber-Arden, Tilmann Kallinich
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Treatment options for autoinflammatory diseases include anti-interleukin (IL)-1 therapies since the IL-1 pathway is crucial in immune dysregulation in patients with monogenic periodic fever syndromes. <h3>Objectives</h3> To gain further insights from routine clinical practice with respect to long-term effectiveness and safety of canakinumab (CAN) in pediatric and adult patients with CAPS (cryopyrin-associated periodic syndrome, including Muckle-Wells syndrome [MWS], familial cold autoinflammatory syndrome [FCAS], neonatal onset multisystem inflammatory disease [NOMID]/chronic infantile neurological cutaneous and articular syndrome [CINCA]), FMF (familial Mediterranean fever<b>)</b>, TRAPS (tumor necrosis factor receptor-associated periodic syndrome) and HIDS/MKD (hyperimmunoglobulinemia D syndrome/mevalonate kinase deficiency). <h3>Methods</h3> RELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a 3-year follow-up enrolling patients aged ≥2 years with clinically confirmed diagnoses who routinely received CAN. 6-monthly clinical assessment and evaluation of patient-reported outcomes is aligned with routine clinic visits. CAPS disease activity was determined by physicians' and patients' assessment. Endpoints were effectiveness and safety of CAN under standard clinical practice conditions. <h3>Results</h3> The interim analysis includes 52 CAPS patients with prior long-term CAN treatment (43.1% females) enrolled by September 2018. 44.2% of the patients participated in the β-Confident study previously. The mean age was 20.7 years (4.0–79.0 years) at baseline and the mean duration of prior CAN treatment was 5.4 years (0.0–11.0 years). 40 patients (76.9%) were diagnosed with MWS, the other patients had FCAS (2), NOMID/CINCA (7) or atypical CAPS (1) (subtype diagnosis of 2 patients not available). Mutations in Nod-like receptor family pyrin domain-containing-3 were identified in 34 patients (68.0%) including E311K (7), Q703K (5), V198M (5), T348M (5), A439V (4). A baseline screening revealed sensorineural hearing loss (62.0%), papillitis (84.0%) and neurological symptoms (71.4%) in patients which had not been detected previously. The majority of patients had no disease related symptoms at baseline and 6 months demonstrating sustained remission in patients receiving long-term CAN treatment. The following disease related symptoms (mild/moderate and severe) were observed in the analysis cohort (N=31) at baseline and 6 months, respectively – disease symptom: baseline (mild/moderate, severe) vs. 6 months (mild/moderate, severe) – urticarial skin rash: 19.4%, 6.5% vs. 25.8%, 0.0%, arthralgia: 32.3%, 0.0% vs. 29.0%, 9.7%, myalgia: 9.7%, 0.0% vs. 16.1%, 0.0%, headaches: 22.6%, 9.7% vs. 19.4%, 19.4%, conjunctivitis: 32.3%, 3.2% vs. 12.9%, 6.5%, abdominal pain: 9.7%, 6.5% vs. 22.6%, 9.7%. Patients' assessment of disease activity and fatigue did not change between baseline and 6 months. However, at baseline 45.5% and after 6 months 76.0% of patients had no impairment of social life by the disease. Serious adverse events were reported for 2 patients (tonsillitis, delivery at week 31). <h3>Conclusion</h3> The RELIANCE study longitudinally monitors the stability of effectiveness of CAN in patients with monogenic periodic fever syndromes. An initial interim analysis including the CAPS subgroup which had prior CAN treatment showed that CAN is an effective and safe treatment in those patients. <h3>Disclosure of Interests:&nbsp;</h3> J. B. Kuemmerle-Deschner Grant/research support from: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis, Consultant for: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis, Speakers bureau: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis, Norbert Blank Grant/research support from: SOBI and Novartis, Speakers bureau: Novartis and SOBI, Michael Borte Grant/research support from: Pfizer and Shire, Ivan Foeldvari Consultant for: Chugai, Novartis, Gerd Horneff: None declared, Prasad Oommen: None declared, Catharina Schuetz: None declared, Frank Weller-Heinemann: None declared, Julia Weber-Arden Employee of: Novartis, Tilmann Kallinich Grant/research support from: Novartis, Speakers bureau: Sobi, Roche, Novartis, CLB