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OP0092 (2021)
LONG-TERM SAFETY AND EFFECTIVENESS OF CANAKINUMAB IN CRYOPYRIN-ASSOCIATED PERIODIC SYNDROMES (CAPS) – 30-MONTH DATA FROM THE RELIANCE REGISTRY
J. B. Kuemmerle-Deschner1, B. Kortus-Goetze2, P. Oommen3, A. Janda4, J. Rech5, T. Kallinich6, F. Weller-Heinemann7, G. Horneff8, I. Foeldvari9, C. Schuetz10, M. Borte11, A. Braner12, J. Weber-Arden13, N. Blank14
1University Hospital Tuebingen, Department of Pediatrics, Division of Pediatric Rheumatology, Tuebingen, Germany
2University of Marburg, Division of Nephrology, Marburg, Germany
3Heinrich-Heine-University Düsseldorf, Clinic of Pediatric Hematology, Oncology and Clinical Immunology, Duesseldorf, Germany
4University Hospital Ulm, Department of Pediatrics, Ulm, Germany
5Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Department of Internal Medicine 3 - Rheumatology and Immunology, Erlangen, Germany
6Charité University Medicine Berlin, Department of Pediatrics, Division of Pulmonology, Immunology and Critical Care Medicine, Berlin, Germany
7Klinikum Bremen-Mitte, Prof. Hess Kinderklinik, Bremen, Germany
8Asklepios Clinic Sankt Augustin, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany
9Centre for Pediatric and Adolescence Rheumatology, Centre for Pediatric and Adolescence Rheumatology, Hamburg, Germany
10Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Pediatrics, Dresden, Germany
11Hospital St. Georg gGmbH Leipzig, ImmunoDeficiencyCenter Leipzig (IDCL), Leipzig, Germany
12University Hospital Frankfurt, Department of Medicine II, Rheumatology, Frankfurt, Germany
13Novartis Pharma GmbH, Novartis Pharma GmbH, Nuernberg, Germany
14University Hospital Heidelberg, Rheumatology, Heidelberg, Germany

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.

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

Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 50
Session: Infection-related rheumatic and orphan diseases (Oral Presentations)