ArticleAnnals of the rheumatic diseases2019
Development and validation of a methotrexate adherence assay.
Article in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Monocytes from inflammatory arthritis patients accumulate methotrexate and their transcriptome predicts methotrexate clinical response.Cellular and molecular life sciences : CMLS · 2026Article
- Comparative Effectiveness of Abatacept Versus Adalimumab in Shared Epitope Positive and Negative Patients With Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Development of a Complex Biofeedback-Based Intervention to Improve Methotrexate Adherence in Rheumatoid Arthritis: A COM-B Model Informed Qualitative Study.Patient preference and adherence · 2026Article
- CD80 Antibody and MTX Co-Engineered Extracellular Vesicles Targets CD80International journal of nanomedicine · 2025Article
- Simultaneous Determination of Unbound Plasma Concentration of Methotrexate and 7-Hydroxymethotrexate in Children Patients Receiving High-Dose Methotrexate Therapy.Drug design, development and therapy · 2025Article
- Towards new approach methodologies for biological therapeutics: a novel model-informed metric to assess immunogenicity risk.Frontiers in immunology · 2025Article
- Therapeutic Drug Monitoring of Low Methotrexate Doses for Drug Exposure and Adherence Assessment-Pre-Analytical Variables, Bioanalytical Issues, and Current Clinical Applications.International journal of molecular sciences · 2024Review
- Urinary methotrexate dosage in rheumatoid arthritis, in patients treated for at least 6 months: a potential marker of adherence.RMD open · 2024Article
- The use of serum methotrexate level as an assessment of biochemical drug adherence in psoriasis.The British journal of dermatology · 2024Article
- Adherence to low-dose methotrexate in children with juvenile idiopathic arthritis using a sensitive methotrexate assay.Pediatric rheumatology online journal · 2024Observational
- Advancing precision rheumatology: applications of machine learning for rheumatoid arthritis management.Frontiers in immunology · 2024Review
- Methotrexate plus electroacupuncture reduces autophagy in ankle synovial tissue in rats with rheumatoid arthritis.American journal of translational research · 2023Article
- Quantitation of methotrexate polyglutamates in human whole blood, erythrocytes and leukocytes collected via venepuncture and volumetric absorptive micro-sampling: a green LC-MS/MS-based method.Analytical and bioanalytical chemistry · 2022Article
- Article
- Real-world evidence on methotrexate-free subcutaneous tocilizumab therapy in patients with rheumatoid arthritis: 24-week data from the SIMPACT study.Rheumatology advances in practice · 2022Article
- Translating research into clinical practice: quality improvement to halve non-adherence to methotrexate.Rheumatology (Oxford, England) · 2021Article
- Relationship Between the Free and Total Methotrexate Plasma Concentration in Children and Application to Predict the Toxicity of HD-MTX.Frontiers in pharmacology · 2021Article
- Could a methotrexate blood assay improve adherence?Nature reviews. Rheumatology · 2019Article
Corrections and comments
- Commented on by
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe 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.
objectiveTo 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.
methods20 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).
resultsA 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%.
conclusionNon-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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.