ArticleOpen access rheumatology : research and reviews2021
Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study.
Article in Open access rheumatology : research and reviews, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Development and Validation of the Medication Adherence Scale for Iraqi Patients with Rheumatoid Arthritis (MASIPRA): A Cross-Sectional Study.Patient preference and adherence · 2026Article
- Leveraging mathematical modeling to analyze nonadherence for hydroxyurea therapy in sickle cell disease.CPT: pharmacometrics & systems pharmacology · 2023Article
- Should we stop methotrexate or not for vaccination?RMD open · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionPatients rarely, if ever, take their medications exactly as prescribed. The extent to which missed doses interfere with a drug's therapeutic effect remains unclear.
methodsAfter 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.
resultsFor 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.
conclusionWhile 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.
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