Subcutaneous Abatacept in Patients With Polyarticular‐Course Juvenile Idiopathic Arthritis

Abstract

ObjectiveTo investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular‐course juvenile idiopathic arthritis (JIA).MethodsIn this phase III, open‐label, international, multicenter, single‐arm study, patients with polyarticular JIA (cohort 1, ages 6–17 years and cohort 2, ages 2–5 years) in whom treatment with ≥1 disease‐modifying antirheumatic drug was unsuccessful received weight‐tiered SC abatacept weekly: 10 to <25 kg (50 mg), 25 to <50 kg (87.5 mg), ≥50 kg (125 mg). Patients who had met the JIA–American College of Rheumatology 30% improvement criteria (achieved a JIA‐ACR 30 response) at month 4 were given the option to continue SC abatacept to month 24. The primary end point was the abatacept steady‐state serum trough concentration (Cminss) in cohort 1 at month 4. Other outcome measures included JIA‐ACR 30, 50, 70, 90, 100, and inactive disease status, the median Juvenile Arthritis Disease Activity Score in 71 joints using the C‐reactive protein level (JADAS‐71–CRP) over time, safety, and immunogenicity.ResultsThe median abatacept Cminss at month 4 (primary end point) and at month 24 was above the target therapeutic exposure (10 μg/ml) in both cohorts. The percentage of patients who had achieved JIA‐ACR 30, 50, 70, 90, or 100 responses or had inactive disease responses at month 4 (intent‐to‐treat population) was 83.2%, 72.8%, 52.6%, 28.3%, 14.5%, and 30.1%, respectively, in cohort 1 (n = 173) and 89.1%, 84.8%, 73.9%, 58.7%, 41.3%, and 50.0%, respectively, in cohort 2 (n = 46); the responses were maintained to month 24. The median (interquartile range) JADAS‐71–CRP improved from baseline to month 4: cohort 1, from 21.0 (13.5, 30.3) to 4.6 (2.1, 9.4); cohort 2, from 18.1 (14.0, 23.1) to 2.1 (0.3, 4.4). Improvements were sustained to month 24, at which time 27 of 173 patients (cohort 1) and 11 of 22 patients (cohort 2) had achieved JADAS‐71–CRP remission. No unexpected adverse events were reported; 4 of 172 patients (2.3%) in cohort 1 and 4 of 46 (8.7%) in cohort 2 developed anti‐abatacept antibodies, with no clinical effects.ConclusionWeight‐stratified SC abatacept yielded target therapeutic exposures across age and weight groups, was well tolerated, and improved polyarticular JIA symptoms over 24 months.

Maintenance of antibody response to diphtheria/tetanus vaccine in patients aged 2–5 years with polyarticular-course juvenile idiopathic arthritis receiving subcutaneous abatacept

“…A safety summary of cohort 2 is presented in Table 3. Abatacept safety profile was consistent between age cohorts [6]. Related serious adverse events (SAEs), SAEs and related AEs were reported in a higher proportion of patients who participated versus those who did not participate in this substudy.…”

“…This substudy of a 24-month, Phase III trial (NCT01844518) of SC abatacept in patients (cohort 1: 173 patients aged 6-17 years; cohort 2: 46 patients aged 2-5 years) with active pJIA and inadequate response/intolerance to ≥1 DMARD [6] was conducted across 48 centers worldwide by members of the Paediatric Rheumatology International Trials Organisation [10] and the Pediatric Rheumatology Collaborative Study Group [11]. Patients received weight-tiered weekly SC abatacept (10-< 25 kg [50 mg], 25-< 50 kg [87.5 mg]) for 4 months.…”

“…Stable doses of concomitant MTX (≤30 mg/m 2 / week) and low-dose oral corticosteroids (≤10 mg/day or ≤ 0.2 mg/kg/day [whichever was less] prednisone equivalent) were permitted if used at baseline. The concomitant use of a tumour necrosis factor inhibitor (TNFi) was prohibited; 10/46 (22%) patients had prior TNFi treatment (adalimumab, etanercept or tocilizumab) [6]. Patients from cohort 2, with ≥2 continuous months of abatacept treatment, who received diphtheria/tetanus vaccine prior to enrolment and who were consented to participate by their legal guardians, were included in this substudy.…”

“…Professional medical writing and editorial assistance was provided by Lola Parfitt, MRes, at Caudex and was funded by Bristol-Myers Squibb. 6 Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy. 7 Azienda Ospedaliera Universitaria Anna Meyer, Florence, Italy.…”

“…Abatacept, a selective T-cell co-stimulation modulator [5], was effective and well-tolerated in children with pJIA aged 2-17 years (subcutaneous [SC] formulation) [6], and in children aged 6-17 years (intravenous [IV] formulation) [7]. In healthy adults, a single 750-mg dose of IV abatacept did not prevent induction of protective antibodies to tetanus toxoid or standard 23-valent pneumococcal vaccine [8].…”