Background/Purpose: biologic agents have revolutionized the treatment of Juvenile Idiopathic Arthritis (JIA) and other conditions due to their high efficacy and safety. However, with the increased and prolonged use of these agents there is uncertainty regarding adverse events, especially in the long-term. The purpose of this study is to describe and analyse SAEs occurring during biologic therapy in a cohort of patients with JIA.

Methods: unicenter, retrospective longitudinal study based on review of a prospectively built, ad-hoc database and medical records. Observation period was January 2000-December 2011. Demographic data, JIA class, disease duration at start of biologic treatment, time from start of biologic treatment to occurrence of SAEs, type and dosage of biologic agents, total time of biologic therapy, concomitant methotrexate (MTX) and prednisone therapy, system involvement during SAEs, and outcomes were recorded. SAEs were defined as any untoward medical occurrence that occurs during observation and results in death, a life-threatening illness, hospitalization, persistent or significant disability or incapacity, or a medically significant event that jeopardized the health of the patient and required intervention to prevent one of the other outcomes listed.

Results: 218 biologic treatments were administered to 145 JIA patients (83 girls; 63 systemic {SJIA], 35 RF –ve poly, 22 RF +ve poly, 16 enthesitis related, 5 extended oligo and 4 psoriatic). Age at start of biologic therapy: 12 years; disease duration at start of biologic therapy:30 months. One biologic agent was prescribed to 101 children, 2 (sequentially) to 28, 3 to 11, 4 to 5 and 5 to 2 patients. Biologics used:  etanercept (ETA,136 treatments), infliximab (INF, 29), adalimumab (ADA, 25), tocilizumab (TOC, 12), abatacept (ABA, 10), anakinra (ANA, 5), and rituximab (2). MTX was used in combination with biologic therapy in 172 (79 %) cases, prednisone in 80 (37 %). Total time of biologic therapy: 4444 months (3342 corresponding to ETA); median duration of each biologic therapy: 13 months. Eighteen SAEs were recorded in 15 children (11 SJIA): 14 infectious (6 varicella zoster), 2 hematologic, 1 systemic autoimmune, 1 anafilaxis. Symptoms compatible with macrophage activation syndrome developed in 2 patients. SAEs occurred at 3.5 (median) months after start of biologic therapy. SAEs rate was 4.9 per 100 patient-years. SAEs were observed during ETA (11 episodes , 8 % of treatments), TOC (3, 25 %), and INF (1, 3 %), ADA (1, 4 %), ABA (1, 10 %), ANA (1, 20 %) therapy. Median dose of concomitant MTX was 15 mg/week, prednisone 0 mg. All patients required admission (2 ICU) and eventually improved after discontinuation of biologics and appropriate therapy. One SJIA patient on ETA developed a lupus-like disease. No malignancy or TB reactivation were observed.

Conclusion: SAEs arising during biologic therapy are infrequently observed in children with JIA They usually appear during the initial months of therapy. Patients with SJIA are at a higher risk of developing SAEs. Varicella zoster is the more common infection. Multicenter studies and international registries may provide evidence on short- and longer-term, comparative safety of different biologics.

---

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/severe-adverse-events-associated-with-use-of-biologic-therapy-in-juvenile-idiopathic-arthritis-a-single-center-study/