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Abatacept: A Review of the Treatment of Polyarticular-Course Juvenile Idiopathic Arthritis

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Abstract

Juvenile idiopathic arthritis (JIA) encompasses several forms of chronic inflammatory arthritis of unknown etiology presenting in children < 16 years of age, with a minimum symptom duration of 6 weeks. Approximately half of affected children have polyarticular-course JIA (pJIA), a functional concept related to several clinically and genetically heterogeneous JIA categories (systemic, extended oligoarthritis, polyarticular rheumatoid factor-positive or rheumatoid factor-negative, enthesitis-related arthritis, and psoriatic arthritis), which has as its defining feature the involvement of five or more joints during the disease course. Chronic inflammation and joint damage lead to the manifestations of JIA such as pain, limitation of motion, and loss of physical function, all of which negatively impact patients’ quality of life. The American College of Rheumatology recommends initial treatment with a conventional synthetic disease-modifying antirheumatic drug (csDMARD), such as methotrexate (MTX) and, in patients with pJIA who have an inadequate response or intolerance to MTX, the use of a biologic DMARD (bDMARD) such as a tumor necrosis factor inhibitor, abatacept, or tocilizumab. Abatacept selectively modulates the CD80/CD86:CD28 co-stimulatory signal required for full T cell activation, and thus has a distinct mechanism of action upstream of that of other currently available bDMARD treatments for rheumatic diseases. To enable physicians to make informed treatment decisions, it is important to review available data for the existing therapeutic agents. Here, we summarize the current evidence from phase III pivotal trials of intravenous (IV) and subcutaneous (SC) abatacept and from an ongoing registry of patients with JIA treated with abatacept. In the pivotal trials for IV and SC abatacept, either with or without MTX, both formulations demonstrated clinical efficacy, with a high proportion of patients achieving stringent clinical responses, as well as improvements in patient-reported outcomes and a favorable safety profile, particularly with regard to infections.

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Acknowledgements

We thank all PRINTO PRCSG coordinating centers and all investigators who participated in the trials. Details of the principal investigators of the intravenous and subcutaneous abatacept studies can be found in Online Resource 1 (see the electronic supplementary material). We also thank Mary Swingle RN, Protocol Manager at Bristol-Myers Squibb Company, Princeton, New Jersey, USA. Professional medical writing assistance was provided by Katerina Kumpan, PhD, at Caudex and was funded by Bristol-Myers Squibb Company.

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Authors and Affiliations

  1. Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA

    Hermine I. Brunner & Daniel J. Lovell

  2. College of Medicine, University of Cincinnati, Cincinnati, OH, USA

    Hermine I. Brunner

  3. Bristol-Myers Squibb Company, Princeton, NJ, USA

    Robert Wong, Tzuyung D. Kou & Alyssa Dominique

  4. Bristol-Myers Squibb Company, Braine-L’Alleud, Belgium

    Marleen Nys

  5. Istituto Giannina Gaslini, University of Genoa, Genoa, Italy

    Alberto Martini

  6. IRCCS Istituto Giannina Gaslini, Clinica Pediatrica E Reumatologia-PRINTO, Genoa, Italy

    Nicolino Ruperto

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  1. Hermine I. Brunner
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for the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)

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Correspondence to Hermine I. Brunner.

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Funding

Studies cited in this review were funded by Bristol-Myers Squibb Company. The review was commissioned by Pediatric Drugs and funded by Bristol-Myers Squibb Company.

Conflict of interest

HIB: speaker fees: Novartis and Roche; grant/research support: Bristol-Myers Squibb Company and Pfizer; consulting fees: AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb Company, EMD Serono, Enzyvant, Genentech/Roche, GlaxoSmithKline, Janssen, Lilly, Novartis, R-Pharm, and UCB. RW, MN, TDK, and AD: shareholders and stakeholders of Bristol-Myers Squibb Company. AM: consulting fees from Janssen, Novartis, and Pfizer. Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia has received consulting fees from AbbVie, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, Pfizer, and R-Pharm for the work of AM. DJL: speakers’ bureau: Bristol-Myers Squibb Company and Genentech; data and safety monitoring board: Forest Research and the National Institutes of Health-NIAMS. Cincinnati Children’s Hospital Medical Center has received consulting fees from AbbVie, AstraZeneca, Bristol-Myers Squibb Company, Centocor, F. Hoffmann-La Roche, Genentech, Novartis, Pfizer, Regeneron, UCB, and XOMA for the work of DJL. NR: grant/research support (paid to the Istituto Giannina Gaslini Hospital): Bristol-Myers Squibb Company, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, and Swedish Orphan Biovitrum (Sobi) (this funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties); speaker fees/honoraria: AbbVie, Ablynx, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb Company, Eli Lilly, EMD Serono, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, and Takeda.

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Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Author contributions

HIB, AM, DJL, and NR had a pivotal and critical role in the design, implementation, analysis, and reporting of the intravenous and subcutaneous abatacept pivotal juvenile idiopathic arthritis trials. The manuscript was drafted and revised critically by the named authors.

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Brunner, H.I., Wong, R., Nys, M. et al. Abatacept: A Review of the Treatment of Polyarticular-Course Juvenile Idiopathic Arthritis. Pediatr Drugs 22, 653–672 (2020). https://doi.org/10.1007/s40272-020-00422-2

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