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Oral to subcutaneous methotrexate dose-conversion strategy in the treatment of rheumatoid arthritis

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Abstract

Both the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) guidelines recommend the use of methotrexate (MTX) for the treatment of rheumatoid arthritis (RA) when there is no contraindication. While MTX is the foundation of RA therapy (Singh et al. in Arthritis Care Res 64:625–639,2012), absorption saturation compromises its oral bioavailability (BA). Differences in the relative BA of oral versus subcutaneous (SC) MTX demonstrate the need for guidance on successful dose-conversion strategies. This study was designed to compare MTX PK profiles as a result of MTX administration via three different treatment administrations: oral, SC MTX administered via an auto-injector (MTXAI) into the abdomen (MTXAIab) and into the thigh (MTXAIth). In this paper, we establish a dose-conversion method based on the BA of MTX from oral and SC administration. SC administration provided higher exposure of MTX than the same dose given orally. Unlike the exposure limitations of oral MTX, dose-proportional exposure was seen with SC MTX.

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Acknowledgements

We would like to thank the patients enrolled in the study, the principal investigators: Stephen A. Bookbinder, Alan J. Kivitz, David A. McLain, and Joel C. Silverfield. Medical writing assistance for AXON Communications was funded by Antares Pharma, Inc.

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Authors and Affiliations

  1. Division of Rheumatology, University of Colorado, Denver, CO, USA

    Michael H. Schiff

  2. Antares Pharma Inc., Minneapolis, MN, USA

    Peter Sadowski

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  1. Michael H. Schiff
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Correspondence to Michael H. Schiff.

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Conflict of interest

Michael Schiff has received consulting fees from AbbVie, Amgen, Antares, Bristol-Myers Squibb, Janssesn, and Eli Lilly; he has received speaker honorarium for AbbVie. Peter Sadowski is an employee of Antares Pharma, Inc. and owns stock in Antares Pharma, Inc.

Human and animal rights statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Schiff, M.H., Sadowski, P. Oral to subcutaneous methotrexate dose-conversion strategy in the treatment of rheumatoid arthritis. Rheumatol Int 37, 213–218 (2017). https://doi.org/10.1007/s00296-016-3621-1

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