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Clinical Trial
. 2018 Jul;70(7):1144-1154.
doi: 10.1002/art.40466. Epub 2018 May 20.

Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study

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Free PMC article
Clinical Trial

Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study

Hermine I Brunner et al. Arthritis Rheumatol. .
Free PMC article

Abstract

Objective: To investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular-course juvenile idiopathic arthritis (JIA).

Methods: In 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.

Results: The 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.

Conclusion: Weight-stratified SC abatacept yielded target therapeutic exposures across age and weight groups, was well tolerated, and improved polyarticular JIA symptoms over 24 months.

Trial registration: ClinicalTrials.gov NCT01844518.

Figures

Figure 1
Figure 1
Patient disposition. * = treatment ongoing at time of analysis in 15 patients (32.6%). AEs = adverse events.
Figure 2
Figure 2
Abatacept steady‐state trough concentration (Cminss) in patients ages 6–17 years (cohort 1) by weight group (A) at month 4 (left) and month 24 (right), and patients ages 2–5 years (cohort 2) at months 4 and 24 (B). Cminss was summarized for treated patients (≥1 dose of study medication) with evaluable pharmacokinetic measurements at each time point. Data are shown as box plots. Each symbol represents a single subject. Boxes represent the upper and lower interquartile range. Lines inside the boxes represent the median. Whiskers represent the 5th and 95th percentiles. Dashed lines indicate the target therapeutic concentration.
Figure 3
Figure 3
Juvenile Idiopathic Arthritis–American College of Rheumatology (JIAACR) 30, 50, 70, 90 improvement criteria response rates over time for patients ages 6‐17 years (cohort 1; intent‐to‐treat [ITT] population analysis) (A) and patients ages 2‐5 years (cohort 2; ITT population analysis to month 4 [study part 1], “as‐observed” population analysis thereafter to month 24 [study part 2]) (B). Bars show the 95% confidence intervals. The apparent decrease in response rates at month 24 in cohort 1 reflects a decreased number of patients with available data at this time point and the associated increased proportion of patients imputed as nonresponders due to missing values.
Figure 4
Figure 4
Baseline and post‐baseline Juvenile Arthritis Disease Activity Score in 71 joints using the C‐reactive protein level (JADAS‐71–CRP) in cohort 1 (A) and cohort 2 (B). Values are the median and interquartile range. JADAS‐71–CRP variables included number of active joints, physician's global assessment of disease activity, parent's global assessment of patient well‐being, and laboratory measurement of inflammation, as measured by CRP. Dashed lines show the JADAS‐71–CRP cutoff values for inactive disease, low disease activity, and high disease activity (1, 3.8, and 10.5, respectively) 33, 35.

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