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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.
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BACKGROUND: Reliable data on the course and treatment of pediatric COVID-19 ("corona virus disease 2019") in immunosuppressed patients with rheumatic diseases are missing. AIM: Delineation of individual strategies of the members of the Society for Pediatric Rheumatology (GKJR) in cases of COVID-19. METHODS: In May 2020 all GKJR members were invited to take part in an online survey. Opinion data regarding an approach using disease-modifying anti-rheumatic drugs (DMARD) in cases of COVID-19 as well as the readiness to use new therapeutic agents in patients in different stages of the disease were collected. RESULTS: A total of 71 respondents (27.3% of all contacted pediatric rheumatologists) took part in the survey. Of these 28.2% had treated patients with COVID-19. Over 95% of the respondents did not support a preventive adaptation of the anti-rheumatic treatment during the SARS-CoV2 pandemic. In the case of outpatients under immunosuppression with proven COVID-19 more than 50% of the respondents would refrain from administering intravenous high-dose steroids, cyclophosphamide, anti-CD20 antibodies as well as BAFF, CTLA4 and TNF-alpha blockades. Conversely, >70% of the respondents would continue the treatment with nonsteroidal anti-inflammatory drugs, hydroxychloroquine (HCQ), oral steroids, mycophenolate, IL1 blockade and immunoglobulins (Ig). In the case of inpatients 74.6% of respondents would consider targeted COVID-19 treatment. In stable patients with oxygen treatment (stage I) HCQ (18.3%), azithromycin (16.9%) and Ig (9.9%) were most frequently used. In cases of early signs (stage II) or a manifest cytokine storm (stage III) anakinra (40.8% for stage II and 46.5% for stage III), tocilizumab (26.8% and 40.8%, respectively), steroids (25.4% and 33.8%, respectively) and remdesivir (29.6% and 38.0%, respectively) were most frequently used. The need for a personalized approach based on the current clinical situation was emphasized by many respondents. CONCLUSION: The currently low prevalence of COVID-19 in Germany limits the general clinical experience. Therefore, the presented results have to be interpreted with caution and mostly as hypothetical treatment considerations. It is to be expected that there will always be a limited amount of evidence on pediatric COVID-19; therefore, a continuous and critical exchange of expert opinions on the treatment strategies is important.