Development and validation of a methotrexate adherence assay.
Ann Rheum Dis
; 78(9): 1192-1197, 2019 09.
Article
en En
| MEDLINE
| ID: mdl-31167761
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
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Espectrometría de Masas
/
Metotrexato
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Cromatografía Líquida de Alta Presión
/
Cumplimiento de la Medicación
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Ann Rheum Dis
Año:
2019
Tipo del documento:
Article
País de afiliación:
Reino Unido