Long-term safety and effectiveness of etanercept in JIA: an 18-year experience from the BIKER registry

Abstract

Background: At present, etanercept represents the most commonly prescribed biologic agent for juvenile idiopathic arthritis (JIA) treatment. Children and adolescents with JIA are often treated with etanercept over long periods, sometimes even into adulthood. The objectives of this analysis were to determine the long-term safety of etanercept compared to a biologic-naïve cohort, and to assess the long-term treatment response upon continuous etanercept exposure using data from the German biologics registry (BiKeR). Methods: JIA patients newly exposed to etanercept were documented in the BiKeR registry from January 2001 till March 2019, and baseline characteristics, effectiveness, as well as safety parameters were analysed. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), JADAS-defined minimal disease activity and remission, JIA-American College of Rheumatology (ACR) improvement criteria, as well as ACR-inactive disease definition. Safety assessments were based on adverse events (AE) reports. Results: 2725 new etanercept users with a diagnosis of JIA were registered. Of these, etanercept was received as a first-line biologic by 95.8% and as monotherapy without concomitant methotrexate by 31.5%. After nine years on continuous treatment, 68.1% of patients presented minimal disease activity, 43.1% JADAS-defined remission on drug and 36.6% ACR-inactive disease. JIA-ACR30/50/70/90 response rates were still 82/79/71/54% after 9 years of treatment. Overall, 2053 AEs (34.3/100PY), including 226 serious AEs (SAE, 3.8/100PY), were observed upon etanercept, compared to 1345 AEs [35.6/100PY; p=0.3] and 52 SAEs (1.4/100PY; p=0.0001) in the biologic-naïve cohort. Respective exposure-adjusted rates for etanercept and biologic-naïve patients were 0.9/100PY and 0.2/100PY (p=0.0001) for serious infections, 0.4/100PY and 0.1/100PY (p=0.01) for zoster reactivation, 0.3/100PY and 0.03/100PY (p=0.015) for inflammatory bowel disease, 1.9/100PY and 1.4/100PY (p=0.09) for uveitis. Three and two malignancies were documented in the etanercept and biologic-naïve groups, as well as three and one deaths, respectively. Conclusions: No new safety signal was observed, especially no increased risk for malignancies or autoimmune disorders other than inflammatory bowel disease. However, SAEs and serious infections, though infrequent, were more often reported on etanercept than in biologic-naïve patients. In addition, etanercept demonstrated a long-term maintenance of clinical benefits up to nine years of continuous treatment. Keywords: Juvenile idiopathic arthritis, JIA-treatment, etanercept, TNF-inhibitors, biologics registry, drug surveillance

Fecal microbiota in children with juvenile idiopathic arthritis treated with methotrexate or etanercept

“…It would have been interesting to compare the effect of treatment on different JIA categories, but our study cohort was too small for this. Children with JIA treated with ETN have been found to have an increased risk for IBD [16], and since changes in the gut microbiota have been associated with the development of IBD [35], it is important to further examine the possible effect of ETN treatment on gut microbiota in a larger study.…”

“…In a study on mice with proteoglycaninduced arthritis, treatment with ETN restored an increased gut permeability and changed the microbiota composition to one more similar to that in control mice [15]. On the other hand, a large German register study has shown an increased risk for inflammatory bowel disease (IBD) in children with JIA treated with ETN as monotherapy [16]. This increases the indication for studying the impact of ETN treatment on the gut microbiota in children with JIA.…”