Florence Aeschlimann

Infliximab in pediatric rheumatology patients: a retrospective analysis of infusion reactions and severe adverse events during 2246 infusions over 12 years.

Objective. To describe infusion reactions (IR) and severe adverse events (SAE) associated with infliximab (IFX) in pediatric patients with rheumatologic and ocular inflammatory diseases in a real-world setting. Methods. This is a retrospective chart review of all patients treated with IFX at the pediatric rheumatology division of a university hospital between October 2000 and December 2012. Results. A total of 2446 IFX infusions were given to 82 patients (72% female). IR occurred in 46 infusions (2%) of 14 patients (17%) after a mean IFX treatment time of 340 days (range 41–780); 9/14 patients (64%) experienced repeated IR. IR were classified as mild (26%), moderate (74%), or severe (0%). Indications for IFX were arthritis (60%), uveitis (20%), arthritis and uveitis (13%), and other inflammatory diseases (5%). The most common clinical symptoms were respiratory signs (72%), cutaneous manifestations (69%), and malaise (61%). In 6/14 patients (43%) with IR, IFX was discontinued: 4 patients because of repeated IR and 2 patients wished to stop treatment immediately following a mild IR. The other 8/14 patients (57%) received premedication with high-dose antihistamine (100%), corticosteroids (75%), and IFX dose increase (75%) and continued IFX treatment for a mean followup period of 146 weeks (range 26–537) after the first IR. We observed severe infections in 5/82 patients (6%); other SAE were rare. Conclusion. Mild and moderate IR occurred in 17% of our patients. Treatment with antihistamines and methylprednisolone, and increasing the IFX dose, allowed continued treatment despite IR in > 50% of patients. Other SAE were infrequent.

A5: Detectable Anti-Infliximab Antibodies in Children Treated with Infliximab for Rheumatic Diseases

Infliximab (IFX) is a monoclonal TNF‐alpha inhibiting antibody which is frequently used to treat children with refractory arthritis and uveitis. The most frequent and limiting adverse events are infusion reactions associated with the presence of anti‐drug antibodies.

Prevalence of Anti-infliximab Antibodies and Their Associated Co-factors in Children with Refractory Arthritis and/or Uveitis: A Retrospective Longitudinal Cohort Study.

Objective. Infliximab (IFX) is a monoclonal tumor necrosis factor-α–inhibiting antibody used in children with refractory arthritis and uveitis. Immunogenicity is associated with a lack of clinical response and infusion reactions in adults; data on immunogenicity in children treated with IFX for rheumatic diseases are scarce. We aimed to describe the prevalence of anti-IFX antibodies and determine co-factors associated with anti-IFX antibodies in children with inflammatory rheumatic and ocular diseases. Methods. Consecutive children treated between August 2009 and August 2012 with IFX at our department were included. Blood samples were collected every 6 months before IFX infusion and tested for anti-IFX antibodies by radioimmunoassay. Patients’ charts were retrospectively reviewed for clinical features and analyzed for associations with anti-IFX antibodies. Results. Anti-IFX antibodies occurred in 14/62 children (23%) and 32/253 blood samples (12.6%) after a mean treatment time of 1084 days (range 73–3498). Infusion reactions occurred in 10/62 (16%) children during the treatment period. With continuation of IFX, anti-IFX antibodies disappeared in 7/14 children. In the bivariate analysis, the occurrence of anti-IFX antibodies was associated with younger age at IFX treatment start (mean age 7.01 vs 9.88 yrs, p = 0.003) and infusion reactions (OR 15.0), while uveitis as treatment indication was protective against development of anti-IFX antibodies (OR 0.17), likely because of higher IFX doses. In the multivariate logistic regression, all 3 covariates remained highly significant. Conclusion. Anti-IFX antibodies occurred commonly at any time during IFX treatment. Anti-IFX antibodies were associated with younger age at IFX start, infusion reactions, and arthritis as treatment indication.

Safety of biological agents in paediatric rheumatic diseases: A real-life multicenter retrospective study using the JIRcohorte database

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.

Multicenter retrospective study of biological tolerance in juvenile idiopathic arthritis (jir-cohort)

Ten years after the introduction of biologics in children, we assess the tolerance of these therapies among patients with juvenile idiopathic arthritis (JIA) in pediatric rheumatology centers.

Switch of biotherapies in patients with juvenile idiopathic arthritis: analyses of the JIR cohort data

Biologic treatments have been introduced for Juvenile Idiopathic Arthritis (JIA) treatment in 2000, and have substantially improved the global prognosis of all disease subtypes. However not all patients respond to one biologic and therapeutic effect of one drug may decrease with time.

Prescribed but not approved: biologic agents used without approval in juvenile idiopathic arthritis in Switzerland, France and Belgium

Biologic agents (BA) have profoundly changed the outcome of juvenile idiopathic arthritis (JIA), making inactive disease and clinical remission an achievable goal for treatment. An increasing number of BA has become available in the last 15 years. However, some BA that have been associated to efficacy in some clinical conditions are not approved by legal authority for the use in pediatric population.