LONG-TERM SAFETY of CANAKINUMAB in PATIENTS with AUTOINFLAMMATORY DISEASES-INTERIM ANALYSIS of the RELIANCE REGISTRY

ABSTRACT

Background: Autoinfammatory diseases (AID) are characterized by severe systemic and organ infammation 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/meva-lonate kinase defciency). Methods: RELIANCE is a prospective, non-interventional, observational study based in Germany. Patients with clinically confrmed 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 naso-pharyngitis, increase of infammatory 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 hyper-sensitivity reactions were observed. N=10 (IR 2.36) vaccination reactions were reported (no SAE). Conclusion: The interim data from the RELIANCE study, the longest running real-life canakinumab registry, confrm 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.