(A25) An Observational Post Approval Safety Study of Etanercept and Methotrexate in Treatment of Juvenile Idiopathic Arthritis (JIA) using the German Biologics JIA Registry (BIKER)
Background: A Post-Authorization Safety Study was conducted to evaluate the long-term safety and effectiveness of etanercept (ETN) for juvenile idiopathic arthritis (JIA) in routine clinical practice.
Objectives: To compare the incidence rates of adverse events (AEs), serious AEs (SAEs), and predefined AEs of special interest in pediatric JIA patients treated with ETN vs. methotrexate (MTX). Secondary objectives included evaluation of safety in patients aged 2–4 yrs and effectiveness of ETN in the overall cohort.
Methods: This long-term cohort study (2001–2020) used prospectively collected data from the German BIKER registry (multicenter observational registry monitoring the long-term safety and effectiveness of biologics for JIA). JIA patients aged 2–17 yrs were enrolled at initiation of ETN or MTX. Patients starting MTX were biologic-naïve. Patients were assessed at baseline (BL), 3 mos, 6 mos, and every 6 mos thereafter (including after discontinuation). Safety assessments were based on AE reports. Effectiveness was assessed according to Juvenile Arthritis Disease Activity Score (JADAS) and JIA-American College of Rheumatology (ACR) criteria.
Results: 2885 new ETN users (6560 patient-yrs of exposure [PYE]) and 1517 new MTX users (3894 PYE) were recorded. Patients starting ETN were older, had a longer disease duration, and higher disease activity at BL vs. new MTX users. 2531 (38.5/100 PYE [95% CI 37.1–40.1]) and 1354 AEs (34.8/100 PYE [32.9–36.6]) were reported during ETN or MTX exposure or ≤90 days after discontinuation, respectively. The ETN cohort had numerically higher risks of SAEs (unadjusted relative risk [RR] 2.9 [95% CI 2.1–3.9]), serious infections (RR 4.8 [2.2–10.6]), herpes zoster reactivation (RR 3.7 [1.3–10.6]), inflammatory bowel disease (RR 13.6 [1.8–101]), and malignancies (RR 1.3 [0.4–4.3]) vs. the MTX cohort. In patients aged 2–4 yrs, rates of SAEs and serious infections were higher with ETN vs. MTX, but 95% Cls were wide and not statistically significant. During ETN treatment, a clinically relevant response was documented with JIA-ACR 30/50/70/90 responses in 68%/61%/48%/34% (last follow-up), with a decrease in mean JADAS10 score ± SD from 15.2 ± 7.5 (BL) to 4.0 ± 5.2 (12 mos). Around 60%/38% of patients had JADAS minimal disease activity/JADAS remission at 24 mos; rates remained largely stable for up to 8 yrs of continuous treatment.
Conclusions: This analysis represents the largest studied cohort of ETN-treated JIA patients. While more SAEs and serious infections were observed in ETN-treated patients, overall rates were similar to those observed in other registry studies. Pediatric patients demonstrated a safety profile consistent with adults and no new safety signals were identified. Long-lasting responses to ETN treatment were observed.
