Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study

Alan Morrison,1 Melissa E Stauffer,1,2 Anna S Kaufman1 1ScribCo, Albrightsville, PA, USA; 2Scientific Editing Solutions, Walworth, WI, USACorrespondence: Alan MorrisonScribCo, 111 Gower Road, Albrightsville, PA, 18210, USATel +1 610 389-0843Email scribcopersonnel@gmail.comIntroduction: Patients rare...

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Autores principales:	Morrison A, Stauffer ME, Kaufman AS
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	therapeutic effect adherence pharmacokinetic modeling antirheumatic agents rheumatoid arthritis drug therapy Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/6d002fdb35ce42e59276f3acdccbfe25
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spelling	oai:doaj.org-article:6d002fdb35ce42e59276f3acdccbfe252021-12-02T19:12:45ZEffect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study1179-156Xhttps://doaj.org/article/6d002fdb35ce42e59276f3acdccbfe252021-09-01T00:00:00Zhttps://www.dovepress.com/effect-of-missed-doses-on-the-therapeutic-effect-of-methotrexate-for-r-peer-reviewed-fulltext-article-OARRRhttps://doaj.org/toc/1179-156XAlan Morrison,1 Melissa E Stauffer,1,2 Anna S Kaufman1 1ScribCo, Albrightsville, PA, USA; 2Scientific Editing Solutions, Walworth, WI, USACorrespondence: Alan MorrisonScribCo, 111 Gower Road, Albrightsville, PA, 18210, USATel +1 610 389-0843Email scribcopersonnel@gmail.comIntroduction: Patients rarely, if ever, take their medications exactly as prescribed. The extent to which missed doses interfere with a drug’s therapeutic effect remains unclear.Methods: After weekly oral dosing of methotrexate (MTX) for rheumatoid arthritis, its polyglutamate derivatives (MTXglu) accumulate in red blood cells, where they are markers for the drug’s therapeutic effectiveness. We used Medication Event Monitoring System data and pharmacokinetic modeling to analyze whether missing MTX doses causes the MTXglu level in red blood cells to fall below the range associated with the drug’s clinical effect.Results: For patients initiating oral MTX, the threshold for clinical effectiveness and the steady state level were reached in medians of 6 weeks and 22 weeks, respectively. For patients at steady state who discontinued MTX, the MTXglu level fell below the therapeutic threshold after a median of 3 weeks. After initiating MTX, single missed doses did not cause a loss of therapeutic effect in the median patient if they occurred after 10 weeks, while runs of ≥ 3 consecutive missed doses did cause the MTXglu level to fall below the therapeutic threshold.Conclusion: While there is considerable variation between patients, pharmacokinetic modeling indicates that instances of isolated single missed doses of MTX typically will not cause polyglutamated methotrexate levels in red blood cells to fall below the range associated with the therapeutic effect. Runs of ≥ 3 consecutive missed doses, however, are typically expected to result in a loss of the therapeutic effect.Keywords: therapeutic effect, adherence, pharmacokinetic modeling, antirheumatic agents, rheumatoid arthritis, drug therapyMorrison AStauffer MEKaufman ASDove Medical Pressarticletherapeutic effectadherencepharmacokinetic modelingantirheumatic agentsrheumatoid arthritisdrug therapyDiseases of the musculoskeletal systemRC925-935ENOpen Access Rheumatology: Research and Reviews, Vol Volume 13, Pp 267-274 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	therapeutic effect adherence pharmacokinetic modeling antirheumatic agents rheumatoid arthritis drug therapy Diseases of the musculoskeletal system RC925-935
spellingShingle	therapeutic effect adherence pharmacokinetic modeling antirheumatic agents rheumatoid arthritis drug therapy Diseases of the musculoskeletal system RC925-935 Morrison A Stauffer ME Kaufman AS Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study
description	Alan Morrison,1 Melissa E Stauffer,1,2 Anna S Kaufman1 1ScribCo, Albrightsville, PA, USA; 2Scientific Editing Solutions, Walworth, WI, USACorrespondence: Alan MorrisonScribCo, 111 Gower Road, Albrightsville, PA, 18210, USATel +1 610 389-0843Email scribcopersonnel@gmail.comIntroduction: Patients rarely, if ever, take their medications exactly as prescribed. The extent to which missed doses interfere with a drug’s therapeutic effect remains unclear.Methods: After weekly oral dosing of methotrexate (MTX) for rheumatoid arthritis, its polyglutamate derivatives (MTXglu) accumulate in red blood cells, where they are markers for the drug’s therapeutic effectiveness. We used Medication Event Monitoring System data and pharmacokinetic modeling to analyze whether missing MTX doses causes the MTXglu level in red blood cells to fall below the range associated with the drug’s clinical effect.Results: For patients initiating oral MTX, the threshold for clinical effectiveness and the steady state level were reached in medians of 6 weeks and 22 weeks, respectively. For patients at steady state who discontinued MTX, the MTXglu level fell below the therapeutic threshold after a median of 3 weeks. After initiating MTX, single missed doses did not cause a loss of therapeutic effect in the median patient if they occurred after 10 weeks, while runs of ≥ 3 consecutive missed doses did cause the MTXglu level to fall below the therapeutic threshold.Conclusion: While there is considerable variation between patients, pharmacokinetic modeling indicates that instances of isolated single missed doses of MTX typically will not cause polyglutamated methotrexate levels in red blood cells to fall below the range associated with the therapeutic effect. Runs of ≥ 3 consecutive missed doses, however, are typically expected to result in a loss of the therapeutic effect.Keywords: therapeutic effect, adherence, pharmacokinetic modeling, antirheumatic agents, rheumatoid arthritis, drug therapy
format	article
author	Morrison A Stauffer ME Kaufman AS
author_facet	Morrison A Stauffer ME Kaufman AS
author_sort	Morrison A
title	Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study
title_short	Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study
title_full	Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study
title_fullStr	Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study
title_full_unstemmed	Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study
title_sort	effect of missed doses on the therapeutic effect of methotrexate for rheumatoid arthritis: a pharmacokinetic modeling study
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/6d002fdb35ce42e59276f3acdccbfe25
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Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study

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