Abatacept as Monotherapy and in Combination With Methotrexate in Patients With Juvenile Idiopathic Arthritis: Analysis of 2 Phase III Trials

Nicolino Ruperto; Daniel J Lovell; Alberto Berman; Jordi Anton; Diego O Viola; Bernard Lauwerys; Maria E Rama; John Bohnsack; Johannes Breedt; Michel Fischbach; Thomas Lutz; Kirsten Minden; Mahmood Ally; Nadina Rubio-Pérez; Elisabeth Gervais; Riana Van Zyl; Robert Wong; Margarita Askelson; Alberto Martini; Hermine I Brunner; Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO)

doi:10.3899/jrheum.2022-1320

Abatacept as Monotherapy and in Combination With Methotrexate in Patients With Juvenile Idiopathic Arthritis: Analysis of 2 Phase III Trials

J Rheumatol. 2023 Nov;50(11):1471-1480. doi: 10.3899/jrheum.2022-1320. Epub 2023 Jul 15.

Authors

Nicolino Ruperto¹, Daniel J Lovell², Alberto Berman³, Jordi Anton⁴, Diego O Viola⁵, Bernard Lauwerys⁶, Maria E Rama⁷, John Bohnsack⁸, Johannes Breedt⁹, Michel Fischbach¹⁰, Thomas Lutz¹¹, Kirsten Minden¹², Mahmood Ally¹³, Nadina Rubio-Pérez¹⁴, Elisabeth Gervais¹⁵, Riana Van Zyl¹⁶, Robert Wong¹⁷, Margarita Askelson¹⁷, Alberto Martini¹⁸, Hermine I Brunner; Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO)

Affiliations

¹ N. Ruperto, MD, MPH, IRCCS Istituto Giannina Gaslini, Gaslini Trial Centre/Servizio di Sperimentazioni Cliniche Pediatriche, PRINTO, Genoa, Italy; nicolaruperto@gaslini.org.
² D.J. Lovell, MD, MPH, H.I. Brunner, MD, MSc, MBA, Cincinnati Children's Hospital Medical Center, Division of Rheumatology, Cincinnati, Ohio, USA.
³ A. Berman, MD, Centro Medico Privado De Reumatologia, Rheumatology Section, San Miguel de Tucuman, Argentina.
⁴ J. Anton, MD, PhD, Hospital Sant Joan de Déu, Universitat de Barcelona, Division of Pediatric Rheumatology, Esplugues de Llobregat (Barcelona), Spain.
⁵ D.O. Viola, MD, Instituto CAICI, Rheumatology, Rosario, Argentina.
⁶ B. Lauwerys, PhB, MBChD, PhD, MD, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain & Service de Rhumatologie, Cliniques Universitaires Saint-Luc, now with UCB Pharma, Brussels, Belgium.
⁷ M.E. Rama, MD, Hospital de Niños de la Santísima Trinidad, Rheumatology Section, Cordoba, Argentina.
⁸ J. Bohnsack, MD, Eccles Primary Children's Outpatient Services, Pediatric Rheumatology, Salt Lake City, Utah, USA.
⁹ J. Breedt, MD, Eugene Marais Hospital, Rheumatology Private Practice, Pretoria, South Africa.
¹⁰ M. Fischbach, MD, Hautepierre University Hospital, Pediatrics, Strasbourg, France.
¹¹ T. Lutz, MD, Center for Rheumatology, Heidelberg, Germany.
¹² K. Minden, MD, German Rheumatism Research Centre Berlin, and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt - Universität zu Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Berlin, Germany.
¹³ M. Ally, MBChB, University of Pretoria, Pretoria, South Africa.
¹⁴ N. Rubio-Pérez, MD, Universidad Autónoma de Nuevo León, Facultad de Medicina, Departamento de Pediatria, Hospital Universitario "Dr. J. E. González", Monterrey, Nuevo León, Mexico.
¹⁵ E. Gervais, PhD, University Hospital Rheumatology and LITEC Laboratory Poitiers, Rheumatology, Poitiers, France.
¹⁶ R. Van Zyl, MBChB, Universitas Hospital, Department of Paediatrics and Child Health, University of the Free State, Bloemfontein, South Africa.
¹⁷ R. Wong, MD, M. Askelson, MS, Bristol Myers Squibb, Princeton, New Jersey, USA.
¹⁸ A. Martini, MD, Università degli Studi di Genova, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Genoa, Italy.

PMID: 37453737
DOI: 10.3899/jrheum.2022-1320

Abstract

Objective: To describe the efficacy and safety data of children with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with abatacept (ABA) + methotrexate (MTX) or ABA monotherapy when prior MTX use was either ineffective or not tolerated.

Methods: Posthoc analysis of 2 phase III trials of subcutaneous (SC) and intravenous (IV) ABA over 2 years in patients with pcJIA (aged 2-17 years). Patients were stratified by treatment with ABA + MTX or ABA monotherapy and further by prior biologic use. Efficacy outcomes included JIA-American College of Rheumatology (JIA-ACR) responses, Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein (JADAS27-CRP), and safety. Descriptive pharmacokinetic analyses were also performed.

Results: Efficacy responses (JIA-ACR and JADAS27-CRP) were similar between patients receiving ABA + MTX (n = 310) or ABA monotherapy (n = 99) and persisted over 2 years. Clinical response rates were similar in biologic-naïve patients and prior biologic users; this was independent of MTX use. Across both studies, ABA + MTX and ABA monotherapy displayed similar safety profiles. Pharmacokinetic results revealed similar minimum steady-state trough ABA concentrations between studies. Further, baseline MTX did not influence ABA clearance and was not a significant predictor of JIA-ACR responses.

Conclusion: ABA monotherapy (SC and IV) was effective and well tolerated in children with pcJIA when prior MTX use was ineffective or not tolerated. Treatment effects of ABA appear to be independent of MTX coadministration. Consequently, ABA monotherapy can be considered for those with prior biologic therapy if MTX use is inappropriate. (ClinicalTrials.gov: NCT01844518 and NCT00095173).

Keywords: biological therapy; disease-modifying antirheumatic drugs; juvenile idiopathic arthritis; methotrexate.

Publication types

Clinical Trial, Phase III
Research Support, Non-U.S. Gov't

MeSH terms

Abatacept / therapeutic use
Antirheumatic Agents* / adverse effects
Arthritis, Juvenile* / chemically induced
Arthritis, Juvenile* / drug therapy
Biological Products* / therapeutic use
Child
Drug Therapy, Combination
Humans
Methotrexate / therapeutic use
Treatment Outcome

Substances

Methotrexate
Abatacept
Antirheumatic Agents
Biological Products

Associated data

ClinicalTrials.gov/NCT00095173
ClinicalTrials.gov/NCT01844518