Florence A Aeschlimann1, Shu-Ling Chong2, Todd W Lyons3, Beate C Beinvogl4, Lina Maria Góez-Mogollón5, Sally Tan6, Ronald M Laxer7. 1. Pediatric Immunology-Hematology and Rheumatology Unit, University Hospital Necker-Enfants Malades, Paris, France. Electronic address: florence.aeschlimann@aphp.fr. 2. Department of Emergency Medicine, KK Women's and Children's Hospital and Duke-NUS Medical School, Singapore, Singapore. 3. Division of Emergency Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA. 4. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA. 5. Ammon-Pinizzotto Center for Women's Mental Health, Massachusetts General Hospital, Boston, MA. 6. Department of Medicine, Brigham and Women's Hospital, Boston, MA. 7. Division of Rheumatology, The Hospital for Sick Children, Department of Pediatrics and Medicine, University of Toronto, Toronto, Ontario, Canada.
Abstract
OBJECTIVE: To assess whether treatment with biologic response modifying agents during clinical trial study periods increases the risk of serious infections in children with juvenile idiopathic arthritis (JIA). STUDY DESIGN: A systematic literature review using Medline, Embase, Cochrane library, and the clinical trial registry was performed up to July 2017. Random effects meta-analyses were used to compare rates of serious infections in children with JIA given biologic agents compared with controls, and the pooled relative risk calculated. Subanalyses were performed for different biologic agent classes. RESULTS: In total, 19 trials accounting for 21 individual studies were included (11 for tumor necrosis factor-alpha inhibitors [n = 814 patients], 3 for interleukin-6 inhibitors [n = 318], 6 for interleukin-1 inhibitors [n = 353], and 1 for selective T-lymphocyte costimulation modulators [n = 122]). Patients (68% female) had a mean age of 10.8 years. Seventeen serious infections were reported among 810 children receiving biologic agents and 15 among 797 controls. The most frequent infections were bronchopulmonary and varicella. No statistically significant difference in risk of serious infections was found between children receiving biologic agents compared with control groups (pooled relative risk = 1.13; 95% CI [0.63, 2.03]) during the trial study periods. The risk remained nonsignificant when evaluating the different classes of biologic agents separately. However, the analyses were underpowered to detect differences in the risk of serious infections overall or differences between classes of biologic agents. CONCLUSIONS: In this systematic review and meta-analyses, serious infections were uncommon and not significantly increased among patients with JIA receiving biologic agents compared with controls. However, the analyses were underpowered and study periods were relatively short. Ongoing careful monitoring for serious infections remains necessary for all patients with JIA, and particularly those receiving biologic agents.
OBJECTIVE: To assess whether treatment with biologic response modifying agents during clinical trial study periods increases the risk of serious infections in children with juvenile idiopathic arthritis (JIA). STUDY DESIGN: A systematic literature review using Medline, Embase, Cochrane library, and the clinical trial registry was performed up to July 2017. Random effects meta-analyses were used to compare rates of serious infections in children with JIA given biologic agents compared with controls, and the pooled relative risk calculated. Subanalyses were performed for different biologic agent classes. RESULTS: In total, 19 trials accounting for 21 individual studies were included (11 for tumor necrosis factor-alpha inhibitors [n = 814 patients], 3 for interleukin-6 inhibitors [n = 318], 6 for interleukin-1 inhibitors [n = 353], and 1 for selective T-lymphocyte costimulation modulators [n = 122]). Patients (68% female) had a mean age of 10.8 years. Seventeen serious infections were reported among 810 children receiving biologic agents and 15 among 797 controls. The most frequent infections were bronchopulmonary and varicella. No statistically significant difference in risk of serious infections was found between children receiving biologic agents compared with control groups (pooled relative risk = 1.13; 95% CI [0.63, 2.03]) during the trial study periods. The risk remained nonsignificant when evaluating the different classes of biologic agents separately. However, the analyses were underpowered to detect differences in the risk of serious infections overall or differences between classes of biologic agents. CONCLUSIONS: In this systematic review and meta-analyses, serious infections were uncommon and not significantly increased among patients with JIA receiving biologic agents compared with controls. However, the analyses were underpowered and study periods were relatively short. Ongoing careful monitoring for serious infections remains necessary for all patients with JIA, and particularly those receiving biologic agents.
Authors: Franz Thiele; Ariane Klein; Daniel Windschall; Anton Hospach; Ivan Foeldvari; Kirsten Minden; Frank Weller-Heinemann; Gerd Horneff Journal: Rheumatol Int Date: 2021-02-16 Impact factor: 2.631