Pharmacovigilance in juvenile idiopathic arthritis patients (pharmachild) treated with biologic agents and/or methotrexate. A Pediatric Rheumatology International Trials Organisation (PRINTO)/Pediatric Rheumatology European Society (PRES) registry

Introduction: Pharmacovigilance in Juvenile Idiopathic Arthritis Patients Treated with Biologic Agents and/or Methotrexate (Pharmachild) is an international registry involving 86 centres in 32 countries from the Paediatric Rheumatology INternational Trials Organisation (PRINTO)/ Paediatric Rheumatology European Society (PReS). The registry was set up in 2011 to evaluate long term safety and efficacy profile of immunosuppressive treatments in children with Juvenile Idiopathic Arthritis (JIA). Objectives: To present data coming from the Pharmachild/PRINTO registry and analyze infections, with a main focus on opportunistic, also evaluating the relationship between infections and biologic and synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs) in children affected by JIA. Methods: We provided descriptive statistics for demographic, clinical data, drug exposure, adverse events (AE) and events of special interest (ESI). Data from Pharmachild were combined with those coming from two national registries: BiKeR from Germany and the Swedish registry. The analysis was then focused on infections. A panel of specialists in infectious and rheumatologic diseases, identified as Safety Adjudication Committee (SAC), elaborated and approved by consensus, through three Delphi steps, a list of opportunistic pathogens for use in immunosuppressed children. Primary objective of the SAC was to adjudicate the infectious events encountered by the patients in Pharmachild with particular attention on opportunistic infections (OI). Results: Data from 8,274 patients were reported from the Pharmachild registry, and combined with those from 3,990 and 3,020 patients from the Germany and the Swedish registries, respectively, for a total of 15,284 patients. The main differences between Pharmachild and the other two registries were found in the age of onset, in the distribution of the different categories of AIG and in the use of biological drugs. The most frequently reported AE in Pharmachild resulted to be infections, adjudicated by the SAC mostly as common (88.4%). A high percentage (17.4%) of OI was reported. Among all infectious events, herpes zoster and mycobacterial infections were the most frequent. A list of OI in pediatrics was identified for subjects with JIA. Conclusions: Registries represent a powerful tool to address important issues on safety in children with JIA treated with immunosuppressive therapy. Their value can be increased by combining individual patient data from different national and international registries. The analysis of the AE in JIA patients has showed that infections are the most frequent event. However they are usually common and not life-threatening.