RT Journal Article
SR Electronic
T1 Development and validation of a methotrexate adherence assay
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1192
OP 1197
DO 10.1136/annrheumdis-2019-215446
VO 78
IS 9
A1 James Bluett
A1 Isabel Riba-Garcia
A1 Suzanne M M Verstappen
A1 Thierry Wendling
A1 Kayode Ogungbenro
A1 Richard D Unwin
A1 Anne Barton
YR 2019
UL http://ard.bmj.com/content/78/9/1192.abstract
AB 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.