Natalia Cabrera1, Jean-Christophe Lega2, Behrouz Kassai3, Carine Wouters4, Anuela Kondi5, Elvira Cannizzaro6, Andreas Woerner7, Aurelie Chausset8, Samuel Roethlisberger9, Cyril Jeanneret9, Florence Aeschlimann6, Salma Malik10, Agnès Duquesne11, Daniela Kaiser12, Laetitia Higel13, Anne Maes4, Gerald Berthet14, Veronique Hentgen15, Isabelle Kone-Paut5, Alexandre Belot11, Michael Hofer7. 1. UMR CNRS 5558, Laboratoire de Biométrie et Biologie Humaine, Équipe Évaluation et Modélisation des Effets Thérapeutiques, rue Guillaume-Paradin, BP8071, 69376 Lyon cedex 08, France; Inserm U1111, National Referral Centre for rare Juvenile Rheumatological and Auto-immune Diseases (RAISE), Department of Paediatric Rheumatology, Lyon University Hospital, University of Lyon, 69677 Bron cedex, France. Electronic address: natalia.rojas@etu.univ-lyon1.fr. 2. UMR CNRS 5558, Laboratoire de Biométrie et Biologie Humaine, Équipe Évaluation et Modélisation des Effets Thérapeutiques, rue Guillaume-Paradin, BP8071, 69376 Lyon cedex 08, France; National Referral Centre for rare Juvenile Rheumatological and Auto-immune Diseases (RAISE), Department of Internal and Vascular Medicine, Hôpital Lyon Sud, Lyon University Hospital, University of Lyon, 69495 Pierre-Bénite, France. 3. UMR CNRS 5558, Laboratoire de Biométrie et Biologie Humaine, Équipe Évaluation et Modélisation des Effets Thérapeutiques, rue Guillaume-Paradin, BP8071, 69376 Lyon cedex 08, France; Clinical Investigation Center (CIC1407), Lyon University Hospital, 69003 Lyon, France. 4. Department of Paediatrics, University Hospitals Leuven, Leuven, Belgium; Department of Immunology and Microbiology, Childhood Immunology, University of Leuven, 3000 Leuven, Belgium. 5. Department of Paediatrics and Paediatric Rheumatology, Centre de référence des maladies auto-inflammatoires rares et de l'amylose inflammatoire (CEREMAIA), Bicêtre University, Paris Sud Hospital, 94270 Le Kremlin-Bicêtre, France. 6. University Children's Hospital, 8032 Zürich, Switzerland. 7. Paediatric Rheumatology, University of Basel, University Children's Hospital, 4031 Basel, Switzerland. 8. Department of Paediatrics, Estaing Hospital, Clermont-Ferrand University Hospital, 63100 Clermont-Ferrand, France. 9. Paediatric Rheumatology Western Switzerland, Centre Hospitalier Universitaire vaudois (CHUV) 1011 Lausanne and Hospital Universitaire Genève (HUG) 1206 Geneva, Switzerland. 10. Clinical Investigation Center (CIC1407), Lyon University Hospital, 69003 Lyon, France. 11. Inserm U1111, National Referral Centre for rare Juvenile Rheumatological and Auto-immune Diseases (RAISE), Department of Paediatric Rheumatology, Lyon University Hospital, University of Lyon, 69677 Bron cedex, France. 12. Department of Paediatrics, Hospital of Lucerne, 6000 Lucerne, Switzerland. 13. Hautepierre Hospital, University Hospitals Strasbourg, 67200 Strasbourg, France. 14. Department of Paediatrics, Hospital of Aarau, 5001 Aarau, Switzerland. 15. Centre de référence des maladies auto-inflammatoires rares et de l'amylose inflammatoire (CEREMAIA), Versailles University Hospital, 78157 Le Chesnay, France.
Abstract
OBJECTIVE: To analyse and report the incidence of side effects of biological agents in paediatric patients with inflammatory diseases using of real-life follow-up cohort. METHODS: In this international, observational, retrospective, multicentre study of children treated by biological agents and followed in the Juvenile Inflammatory Rheumatism (JIR) cohort (JIRcohorte) network, a Kaplan-Meier method was used to estimate the occurrence of adverse events. A Cox model was constructed to identify independent predictors of adverse events. RESULTS: Overall 813 patients totalling 3439 patients-year (PY) of biological agents were included. The main diagnosis was juvenile idiopathic arthritis (84%). A total of 222 patients (27.3%) had 419 adverse events, representing an incidence rate of 12.2 per 100 PY 95% CI [11.0; 13.4]. The overall incidence rate of serious adverse events was 3.9 per 100 PY 95% CI [3.2; 4.6]. Tocilizumab and infliximab were significantly associated with adverse events and canakinumab with serious adverse events. Univariate and multivariable analysis of adverse events and serious adverse events indicated that patients under biological agents with concomitant immunosuppressive drugs (excluding methotrexate) suffered from more of these events. CONCLUSION: This study suggests an overall an acceptable safety of biologic agents in children with inflammatory rheumatic diseases treated with biological agents. However, the concomitant prescription of immunosuppressive drugs with biological agents represents a substantial risk of adverse events.
OBJECTIVE: To analyse and report the incidence of side effects of biological agents in paediatric patients with inflammatory diseases using of real-life follow-up cohort. METHODS: In this international, observational, retrospective, multicentre study of children treated by biological agents and followed in the Juvenile Inflammatory Rheumatism (JIR) cohort (JIRcohorte) network, a Kaplan-Meier method was used to estimate the occurrence of adverse events. A Cox model was constructed to identify independent predictors of adverse events. RESULTS: Overall 813 patients totalling 3439 patients-year (PY) of biological agents were included. The main diagnosis was juvenile idiopathic arthritis (84%). A total of 222 patients (27.3%) had 419 adverse events, representing an incidence rate of 12.2 per 100 PY 95% CI [11.0; 13.4]. The overall incidence rate of serious adverse events was 3.9 per 100 PY 95% CI [3.2; 4.6]. Tocilizumab and infliximab were significantly associated with adverse events and canakinumab with serious adverse events. Univariate and multivariable analysis of adverse events and serious adverse events indicated that patients under biological agents with concomitant immunosuppressive drugs (excluding methotrexate) suffered from more of these events. CONCLUSION: This study suggests an overall an acceptable safety of biologic agents in children with inflammatory rheumatic diseases treated with biological agents. However, the concomitant prescription of immunosuppressive drugs with biological agents represents a substantial risk of adverse events.