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

Fecha de publicación: 01/07/2018

Autores de IIS La Fe

Inmaculada Calvo Penadés

Autor

Participantes ajenos a IIS La Fe

Brunner, HI
Tzaribachev, N
Vega-Cornejo, G
Louw, I
Berman, A
Anton, J
Avila-Zapata, F
Cuttica, R
Horneff, G
Foeldvari, I
Keltsev, V
Kingsbury, DJ
Viola, DO
Joos, R
Lauwerys, B
Gastanaga, MEP
Rama, ME
Wouters, C
Bohnsack, J
Breedt, J
Fischbach, M
Lutz, T
Minden, K
Mirava, T
Ally, MMTM
Rubio-Perez, N
Gervais, ES
Van Zyl, R
Li, XH
Nys, M
Wong, R
Banerjee, S
Lovell, DJ
Martini, A
Ruperto, N
Paediat Rheumatology Int Trials Or
Pediat Rheumatology Collaborative

Grupos

Reumatología Pediátrica

Investigador establecido

Inmaculada Calvo Penadés

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 (C-minss) 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 C-minss at month 4 (primary end point) and at month 24 was above the target therapeutic exposure (10 g/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.

Datos de la publicación

ISSN/ISSNe:: 2326-5191, 2326-5205
Tipo:: Article
Páginas:: 1144-1154
DOI:: 10.1002/art.40466
Factor de Impacto:: 3,952 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Keywords

DISEASE-ACTIVITY SCORE; COSTIMULATION MODULATOR ABATACEPT; LONG-TERM SAFETY; RHEUMATOID-ARTHRITIS; INADEQUATE RESPONSE; INTRAVENOUS ABATACEPT; METHOTREXATE; EFFICACY; CHILDREN; IMMUNOGENICITY