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Development and validation of a methotrexate adherence assay
BACKGROUND: The first-line therapy for rheumatoid arthritis (RA) is weekly oral methotrexate (MTX) at low dosages (7.5–25 mg/week). However, ~40% of patients are non-adherent which may explain why some do not respond and need to start more expensive biological therapies. To monitor adherence more ac...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788879/ https://www.ncbi.nlm.nih.gov/pubmed/31167761 http://dx.doi.org/10.1136/annrheumdis-2019-215446 |
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author | Bluett, James Riba-Garcia, Isabel Verstappen, Suzanne M M Wendling, Thierry Ogungbenro, Kayode Unwin, Richard D Barton, Anne |
author_facet | Bluett, James Riba-Garcia, Isabel Verstappen, Suzanne M M Wendling, Thierry Ogungbenro, Kayode Unwin, Richard D Barton, Anne |
author_sort | Bluett, James |
collection | PubMed |
description | BACKGROUND: The first-line therapy for rheumatoid arthritis (RA) is weekly oral methotrexate (MTX) at low dosages (7.5–25 mg/week). However, ~40% of patients are non-adherent which may explain why some do not respond and need to start more expensive biological therapies. To monitor adherence more accurately and develop strategies to improve it, a validated objective MTX adherence test is required. OBJECTIVE: To develop and validate the diagnostic accuracy of a novel MTX adherence assay using high-performance liquid chromatography–selected reaction monitoring– mass spectrometry (HPLC-SRM-MS) based biochemical analysis of drug levels. METHODS: 20 patients with RA underwent MTX pharmacokinetic assessment using HPLC-SRM-MS MTX plasma concentration analysis over a 6-day period. Directly observed therapy was the reference standard. Pharmacokinetic model validation was performed using independent plasma samples from real-world patients (n=50) with self-reported times of drug administration. Following assay optimisation, the sensitivity of the assay to detect adherence was established using samples from an observational cohort study (n=138). RESULTS: A two-compartment pharmacokinetic model was developed and validated. Simulations described the sensitivity required for MTX detection over 7 days; subsequent assay optimisation and retesting of samples confirmed that all patients were correctly identified as MTX adherers. Using real-world samples, the assays sensitivity was 95%. CONCLUSION: Non-adherence to MTX is common and can have a significant effect on disease activity. HPLC-SRM-MS plasma analysis accurately detects MTX adherence. The validated objective test could easily be used in clinic to identify patients requiring adherence support. |
format | Online Article Text |
id | pubmed-6788879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-67888792019-10-25 Development and validation of a methotrexate adherence assay Bluett, James Riba-Garcia, Isabel Verstappen, Suzanne M M Wendling, Thierry Ogungbenro, Kayode Unwin, Richard D Barton, Anne Ann Rheum Dis Rheumatoid Arthritis BACKGROUND: The first-line therapy for rheumatoid arthritis (RA) is weekly oral methotrexate (MTX) at low dosages (7.5–25 mg/week). However, ~40% of patients are non-adherent which may explain why some do not respond and need to start more expensive biological therapies. To monitor adherence more accurately and develop strategies to improve it, a validated objective MTX adherence test is required. OBJECTIVE: To develop and validate the diagnostic accuracy of a novel MTX adherence assay using high-performance liquid chromatography–selected reaction monitoring– mass spectrometry (HPLC-SRM-MS) based biochemical analysis of drug levels. METHODS: 20 patients with RA underwent MTX pharmacokinetic assessment using HPLC-SRM-MS MTX plasma concentration analysis over a 6-day period. Directly observed therapy was the reference standard. Pharmacokinetic model validation was performed using independent plasma samples from real-world patients (n=50) with self-reported times of drug administration. Following assay optimisation, the sensitivity of the assay to detect adherence was established using samples from an observational cohort study (n=138). RESULTS: A two-compartment pharmacokinetic model was developed and validated. Simulations described the sensitivity required for MTX detection over 7 days; subsequent assay optimisation and retesting of samples confirmed that all patients were correctly identified as MTX adherers. Using real-world samples, the assays sensitivity was 95%. CONCLUSION: Non-adherence to MTX is common and can have a significant effect on disease activity. HPLC-SRM-MS plasma analysis accurately detects MTX adherence. The validated objective test could easily be used in clinic to identify patients requiring adherence support. BMJ Publishing Group 2019-09 2019-06-05 /pmc/articles/PMC6788879/ /pubmed/31167761 http://dx.doi.org/10.1136/annrheumdis-2019-215446 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Rheumatoid Arthritis Bluett, James Riba-Garcia, Isabel Verstappen, Suzanne M M Wendling, Thierry Ogungbenro, Kayode Unwin, Richard D Barton, Anne Development and validation of a methotrexate adherence assay |
title | Development and validation of a methotrexate adherence assay |
title_full | Development and validation of a methotrexate adherence assay |
title_fullStr | Development and validation of a methotrexate adherence assay |
title_full_unstemmed | Development and validation of a methotrexate adherence assay |
title_short | Development and validation of a methotrexate adherence assay |
title_sort | development and validation of a methotrexate adherence assay |
topic | Rheumatoid Arthritis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788879/ https://www.ncbi.nlm.nih.gov/pubmed/31167761 http://dx.doi.org/10.1136/annrheumdis-2019-215446 |
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