THU0518 EFFICACY AND SAFETY OF ETANERCEPT IN JUVENILE IDIOPATHIC ARTHRITIS – 18 YEAR EXPERIENCE USING DATA OF THE BIKER REGISTRY

Abstract

Background Since 2000, Etanercept is approved for polyarticular juvenile idiopathic arthritis (JIA). Subsequently, approval has been extended to additional JIA categories. Objectives To describe efficacy and safety of Etanercept in clinical practice in JIA patients in comparison to a biologic-naive JIA cohort using the German Biologics registry (BiKeR). Methods Baseline demographics and disease activity parameters were documented. Efficacy was determined using the JADAS10. Safety assessments were based on adverse events reports (AE) processed according to MedDRA. Results Until October 1, 2018, 2645 JIA patients treated with Etanercept were registered, representing 5820 patient-years (PY) of exposure. The total observation time (from date of first dose until last follow-up, censored, if another biologic was started) was calculated as 8080 PY. In general, the cohort treated with Etanercept had experienced disease duration of 4.2+/-3.7 years (mean+/-SD). 2303 patients (87%) were pretreated with methotrexate, 100 with alternative biologics. Concomitantly, 1822 patients (69%) received methotrexate, 2098 (79%) NSAIDs, 949 (36%) systemic corticosteroids as well as further drugs in lower numbers. In the control cohort, 1517 biologic naive JIA patients started methotrexate. At last follow-up, 68%/62%/50%/34% of patients reached JIAACR30/50/70/90 criteria. The median (IQR1-3) JADAS10 score decreased from 15.0 (10-20.4) at baseline to 3.5 (0.7-10.1). 60% of patients achieved a JADAS defined minimal disease activity, 40% reached a JADAS remission. 1924 AE were observed (33.1/100PY [95% CI 31.6-34.6]). 221qualified as SAE (3.8/100PY [3.3-4.3]). These figures were compared to 1292 AE reported during 3714PY in the control cohort (34.8/year [32.9-36.8]) and 52 SAE (1.4/100PY [1.1-1.8]). The most frequent SAE in the Etanercept cohort were grouped in the MedDRA SOC infections and infestations (n=54) followed by musculoskeletal and connective tissue disorders (n=27), eye disorders (n=21), gastrointestinal disorders (n=17) and nervous system disorders (n=15). There were 5 deaths. Serious infections were of bacterial and viral origin and mostly occurred once only. Adverse events of special interest were uveitis (n=109), H. zoster (n=24), chronic inflammatory bowel disease (n=19), pregnancies (n=4), depression (n= 11), malignancies (n=8), demyelination (n=2). Adverse Events of Special Interest (AESI) were in the MTX–cohort uveitis (n=52), H. zoster (n=4), chronic inflammatory bowel disease (n=1), depression (n= 2), malignancies (n=4). A total of 1606 patients (60.7%) discontinued treatment. Of these 638 (39.7%) discontinued due to remission, 565 (35.2%) due to lack of efficacy and 188 (11.7%) because of intolerance. Conclusion The current analysis adds to the established safety profile of Etanercept and demonstrates that the rate of SAEs is comparable and consistent with the overall AE profile in paediatric patients. As expected, infections are the most frequent SAE. Uveitis is likely associated with JIA. Of notice, few patients developed a chronic inflammatory bowel disease and some a malignancy. No new safety signals specific to the paediatric population were identified in this large cohort of JIA patients.