O28. SUBCUTANEOUS ABATACEPT IN PATIENTS WITH POLYARTICULAR-COURSE JUVENILE IDIOPATHIC ARTHRITIS AND INADEQUATE RESPONSE TO BIOLOGIC OR NON-BIOLOGIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS: PHARMACOKINETICS, EFFICACY AND SAFETY

Abstract

Introduction: IV abatacept 10 mg/kg every 4 weeks has proved to be well tolerated and effective in reducing the signs and symptoms of polyarticular juvenile idiopathic arthritis (pJIA).1 In adult RA, weight-tiered IV (~10 mg/kg) and SC abatacept 125 mg weekly have equivalent efficacy and comparable safety;2 therefore, SC abatacept may be similarly beneficial in patients with pJIA. Objective(s): To report 2-year efficacy, safety and pharmacokinetic results of SC abatacept treatment in patients aged 6-17 years with active pJIA. Method(s): Patients with pJIA and inadequate response/intolerance to >1 DMARD were enrolled in two age cohorts (2-5 years and 6-17 years) into this 2-year, single-arm, open-label (OL), Phase III study. Patients received SC abatacept weekly for 4 months based on body weight tier (10-<25 kg [50 mg abatacept]; 25-<50 kg [87.5 mg abatacept]; >50 kg [125 mg abatacept]). JIA-ACR criteria 30 (JIA-ACR30; ACR Pediatric 30) responders at 4 months could enter a 20-month OL extension. The pri-mary endpoint was abatacept steady-state serum trough concentration (Cminss) at 4 months in the 6-17-year cohort. Secondary efficacy outcomes included JIA-ACR30, 50, 70, 90 and inactive disease (no active joints, Physician Global Assessment of disease activity <10 mm, CRP <0.6 mg/dL) response rates. Safety was evaluated throughout the study. Result(s): For the 6-17-year cohort (intent-to-treat, n = 173), baseline median (25th percentile, 75th percentile) age and number of active joints were 13.0 (10.0, 15.0) years and 10.0 (6.0, 19.0), respectively. Number of patients (%) with concomitant use of MTX was 136 (78.6) and with prior biologic use was 46 (26.6). Overall, 132 (76.3%) patients completed the 20-month OL extension period. Robust JIA-ACR30,50, 70,90 and inactive disease responses were seen at 2 years (n = 109): 92.7, 89.0, 83.5, 65.1 and 57.9%, respectively. No new or unexpected safety concerns were reported (Table 17). Mean (SD) Cminss value was stable over the 2-year period, ranging from 40.6 to 47.7 ug/mL, achieving the target therapeutic exposure (Cminss = 10 ug/mL) consistently across all three weight groups. Conclusion(s): In this 2-year analysis of patients with pJIA aged 6-17 years, SC abatacept was well tolerated and demonstrated robust efficacy with no new safety concerns; target therapeutic exposure with SC abatacept was achieved and within the range of abatacept levels observed with IV abatacept in pJIA.