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

the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1144-1154
Number of pages11
JournalArthritis and Rheumatology
Volume70
Issue number7
DOIs
StatePublished - Jul 1 2018

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Juvenile Arthritis
C-Reactive Protein
Joints
Weights and Measures
Abatacept
Safety
Antirheumatic Agents
Rheumatology
Therapeutics
Anti-Idiotypic Antibodies
Pharmacokinetics
Age Groups
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG) (2018). Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study. Arthritis and Rheumatology, 70(7), 1144-1154. https://doi.org/10.1002/art.40466

Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis : Results From a Phase III Open-Label Study. / the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG).

In: Arthritis and Rheumatology, Vol. 70, No. 7, 01.07.2018, p. 1144-1154.

Research output: Contribution to journalArticle

the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG) 2018, 'Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study', Arthritis and Rheumatology, vol. 70, no. 7, pp. 1144-1154. https://doi.org/10.1002/art.40466
the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study. Arthritis and Rheumatology. 2018 Jul 1;70(7):1144-1154. https://doi.org/10.1002/art.40466
the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). / Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis : Results From a Phase III Open-Label Study. In: Arthritis and Rheumatology. 2018 ; Vol. 70, No. 7. pp. 1144-1154.
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title = "Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study",
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.",
author = "{the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)} and Brunner, {Hermine I.} and Nikolay Tzaribachev and Gabriel Vega-Cornejo and Ingrid Louw and Alberto Berman and {Calvo Penad{\'e}s}, Inmaculada and Jordi Ant{\'o}n and Francisco {\'A}vila-Zapata and Rub{\'e}n Cuttica and Gerd Horneff and Ivan Foeldvari and Vladimir Keltsev and Kingsbury, {Daniel J.} and Viola, {Diego Oscar} and Rik Joos and Bernard Lauwerys and {Paz Gasta{\~n}aga}, {Maria Eliana} and Rama, {Maria Elena} and Carine Wouters and John Bohnsack and Johannes Breedt and Michel Fischbach and Thomas Lutz and Kirsten Minden and Tatiana Miraval and Ally, {Mahmood M.T.M.} and Nadina Rubio-P{\'e}rez and {Solau Gervais}, Elisabeth and {van Zyl}, Riana and Xiaohui Li and Marleen Nys and Robert Wong and Subhashis Banerjee and Lovell, {Daniel J.} and Alberto Martini and Nicolino Ruperto and Becker, {Mara L.} and Ilowite, {Norman Todd} and Dare, {Jason A.} and Morris, {Paula K.} and Beukelman, {Timothy G.} and Linda Wagner-Weiner and Lawrence Zemel and Pierre Quartier and Isabelle Kone-Paut and Alexandre Belot and Valeria Gerloni and Manuel Ferrandiz and {Van Rensburg}, {Dina Janse} and Scheibel, {Iloite Maria}",
year = "2018",
month = "7",
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language = "English (US)",
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TY - JOUR

T1 - Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis

T2 - Results From a Phase III Open-Label Study

AU - the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)

AU - Brunner, Hermine I.

AU - Tzaribachev, Nikolay

AU - Vega-Cornejo, Gabriel

AU - Louw, Ingrid

AU - Berman, Alberto

AU - Calvo Penadés, Inmaculada

AU - Antón, Jordi

AU - Ávila-Zapata, Francisco

AU - Cuttica, Rubén

AU - Horneff, Gerd

AU - Foeldvari, Ivan

AU - Keltsev, Vladimir

AU - Kingsbury, Daniel J.

AU - Viola, Diego Oscar

AU - Joos, Rik

AU - Lauwerys, Bernard

AU - Paz Gastañaga, Maria Eliana

AU - Rama, Maria Elena

AU - Wouters, Carine

AU - Bohnsack, John

AU - Breedt, Johannes

AU - Fischbach, Michel

AU - Lutz, Thomas

AU - Minden, Kirsten

AU - Miraval, Tatiana

AU - Ally, Mahmood M.T.M.

AU - Rubio-Pérez, Nadina

AU - Solau Gervais, Elisabeth

AU - van Zyl, Riana

AU - Li, Xiaohui

AU - Nys, Marleen

AU - Wong, Robert

AU - Banerjee, Subhashis

AU - Lovell, Daniel J.

AU - Martini, Alberto

AU - Ruperto, Nicolino

AU - Becker, Mara L.

AU - Ilowite, Norman Todd

AU - Dare, Jason A.

AU - Morris, Paula K.

AU - Beukelman, Timothy G.

AU - Wagner-Weiner, Linda

AU - Zemel, Lawrence

AU - Quartier, Pierre

AU - Kone-Paut, Isabelle

AU - Belot, Alexandre

AU - Gerloni, Valeria

AU - Ferrandiz, Manuel

AU - Van Rensburg, Dina Janse

AU - Scheibel, Iloite Maria

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

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