0275: No Cumulative Effect of Infection Rates in Children Receiving Long-term Canakinumab Treatment in Autoinflammatory Periodic Fever Syndromes − Data from the RELIANCE Registry

Jasmin B. Kuemmerle-Deschner¹, Joerg Henes², Birgit Kortus-Goetze³, Prasad T. Oommen⁴, Anne Pankow⁵, Tilmann Kallinich⁶, Tobias Krickau⁷, Catharina Schuetz⁸, Gerd Horneff⁹, Ivan Foeldvari¹⁰, Juergen Rech¹¹, Frank Weller-Heinemann¹², Ales Janda¹³, Markus Hufnagel¹⁴, Florian M. Meier¹⁵, Frank Dressler¹⁶, Michael Borte¹⁷, Ioana Andreica¹⁸, Peter Wasiliew¹⁹, Michael Fiene²⁰, Daniel Windschall²¹, Martin Krusche²², Tania Kuempfel²³, Julia Weber-Arden²⁴ and Norbert Blank²⁵, ¹med.uni-tuebingen, Tübingen, Germany, ²University Hospital Tuebingen, Tuebingen, Germany, ³Department of Internal Medicine, Division of Nephrology,University Hospital of Giessen and Marburg, Marburg, Germany, ⁴Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health,Medical Faculty Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany, ⁵Department of Rheumatology and Clinical Immunology,Charité-Universitätsmedizin Berlin, Berlin, Germany, ⁶Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Nuremberg, Germany, ⁷Pediatrics, Friedrich-Alexander University Erlangen-Nuernberg (FAU), Erlangen, Germany, ⁸Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus,Technische Universität Dresden, Dresden, Germany, ⁹Asklepios Klinik Sankt Augustin GmbH, Bonn, Germany, ¹⁰Hamburger Zentrum für Kinder- und Jugendrheumatologie, Hamburg, Germany, ¹¹University Clinic Erlangen, Erlangen, Germany, ¹²Division of Pediatric Rheumatology, Prof. Hess Children's Hospital, Bremen, Bremen, Germany, ¹³Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany, ¹⁴Division of Pediatric Infectious Diseases and Rheumatology, Department of Pediatrics and Adolescent Medicine, University Medical Center, Medical Faculty, University of Freiburg, Freiburg, Germany, ¹⁵Department of General Pharmacology and Toxicology, Goethe University Hospital and Goethe University Frankfurt, Frankfurt am Main, Germany, ¹⁶Department of Paediatric Pneumology, Allergology and Neonatology, Children's Hospital, Hannover Medical School, Hannover, Germany, ¹⁷Hospital for Children & Adolescents, St. Georg Hospital, Leipzig, Germany, ¹⁸Rheumazentrum Ruhrgebiet Herne, Herne, Germany, ¹⁹Division of Pediatric Rheumatology and autoinflammation reference center Tuebingen, Department of Pediatrics, University Hospital Tuebingen, Tuebingen, Germany, ²⁰Rheumatology Center Greifswald, Greifswald, Germany, ²¹Clinic of Paediatric and Adolescent Rheumatology, St. Josef-Stift Sendenhorst, Northwest German Center for Rheumatology, Sendenhorst, Germany, ²²UKE, Hamburg, Germany, ²³Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilians Universität München, Muenchen, Germany, ²⁴Novartis Innovative Medicines, Nuernberg, Germany, ²⁵University Hospital Heidelberg, Heidelberg, Germany

Background/Purpose: Autoinflammatory diseases (AID) have been treated safely and effectively with the interleukin-1β inhibitor canakinumab (CAN) in controlled trials and routine clinical practice. The most common adverse event reported were infections. In this study infections and infection rates in patients with cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), hyper-IgD syndrome/mevalonate kinase deficiency (HIDS/MKD) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS) on CAN therapy were investigated in a real-world setting.

Methods: RELIANCE is a prospective, non-interventional, observational study in Germany enrolling pediatric (age ≥2 years) and adult patients with a clinically confirmed diagnosis of AID who routinely receive CAN. Efficacy and safety parameters are recorded at baseline and assessed at 6-month intervals.

Results: The present interim analysis is based on data from a total of n=232 patients including n=101 (44%) pediatric patients under 18 years diagnosed with autoinflammatory diseases enrolled in the RELIANCE registry. The median duration of CAN treatment before and during study in the pediatric cohort was 4 years (0−15 years).

Between 2017 and 2022, 898 adverse events (AE) were recorded in n=164 patients (71%; Table 1). The incidence rate per 100 patient years (IR) was 163.82. Serious adverse events (SAE) were reported for n=35 patients (15%; 98 events, IR 17.88).

During the study, infections occurred in 54.5% of patients (55 patients, 131 AE, including 11 SAE). To closely monitor the impact of long-term CAN treatment on infection rates in pediatric patients, data from a total of n=53, 71, 83 and 80 pediatric patients enrolled in the study in 2019, 2020, 2021, and 2022 were compared (Fig. 1). The IR of non-serious and serious infections in pediatric patients was 75.24 and 10.75 in 2019, and dropped to 44.90 and 4.99 in 2020, and 29.65 and 0.00 in 2021. The IR decrease might be caused by the periods of social distancing during the coronavirus pandemic in 2020 and 2021. In 2022, the IR of non-serious infections increased to 105.50 while the IR of serious infection stayed flat (IR 2.15). The course of upper respiratory tract infections IR in 2019, 2020, 2021, and 2022 was comparable to the IR of non-serious infections: 10.75, 8.32, 1.85, and 10.76. No cumulation of non-serious and serious infections under Canakinumab long-term treatment could be observed in the pediatric cohort.

Conclusion: Interim data of the RELIANCE study confirm that in the pediatric cohort the risk of infections including upper respiratory tract infections does not accumulate over 4 years under CAN treatment.






J. Kuemmerle-Deschner: Novartis, AbbVie, Sobi, 2, 5; J. Henes: AbbVie/Abbott, 2, 6, Boehringer-Ingelheim, 2, 6, Bristol-Myers Squibb(BMS), 2, 6, GlaxoSmithKlein(GSK), 2, 6, Janssen, 2, 6, Novartis, 2, 6, Pfizer, 2, 6, UCB, 2, 6; B. Kortus-Goetze: Novartis, 2; P. Oommen: Novartis, 5; A. Pankow: None; T. Kallinich: Roche, 6; T. Krickau: Novartis, 2, 5, 6; C. Schuetz: Novartis, 5; G. Horneff: GSK, 6, Janssen, 6, MSD, 5, 6, Novartis, 5, 6, Pfizer, 5, 6, Roche, 5, 6, Sanofi, 6, Sobi, 6; I. Foeldvari: Novartis, 2; J. Rech: AbbVie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, 2, 6, Novartis, Sobi, 5; F. Weller-Heinemann: None; A. Janda: None; M. Hufnagel: Novartis, 5; F. Meier: Novartis, 6; F. Dressler: Abbvie, Mylan, Novartis, Pfizer, 2, Novartis, 5; M. Borte: Pfizer, Shire, 5; I. Andreica: AbbVie/Abbott, 1, 6, Amgen, 1, 6, AstraZeneca, 1, 6, Chugai, 6, Novartis, 1, 6, Sobi, 1, 6, UCB, 1, 6; P. Wasiliew: None; M. Fiene: None; D. Windschall: None; M. Krusche: Chugai, 2, 6; T. Kuempfel: None; J. Weber-Arden: Novartis, 3; N. Blank: Novartis, Sobi, 5, Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, 2.