Observational studyRheumatology (Oxford, England)2022
The synergistic efficacy of hydroxychloroquine with methotrexate is accompanied by increased erythrocyte mean corpuscular volume.
Observational study in Rheumatology (Oxford, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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.
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.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Artificial intelligence to predict treatment response in rheumatoid arthritis and spondyloarthritis: a scoping review.Rheumatology international · 2025Article
- An erythrocyte macrocytosis by methotrexate is associated with early initiation of biologic or targeted synthetic agents in patients with rheumatoid arthritis.Journal of rheumatic diseases · 2025Article
- Machine learning-based remission prediction in rheumatoid arthritis patients treated with biologic disease-modifying anti-rheumatic drugs: findings from the Kuwait rheumatic disease registry.Frontiers in big data · 2024Article
- Artificial Intelligence in Rheumatoid Arthritis: Current Status and Future Perspectives: A State-of-the-Art Review.Rheumatology and therapy · 2022Review
- Increased erythrocyte mean corpuscular volume by methotrexate predicts clinical response in psoriatic arthritis.Rheumatology (Oxford, England) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesTo determine whether concomitant HCQ modulates the increase in erythrocyte mean corpuscular volume (MCV) caused by MTX therapy, and whether this is associated with improved clinical response in RA.
methodsA retrospective observational analysis was conducted on two independent hospital datasets of biologic-naïve, early-RA patients who started oral MTX. Baseline characteristics, DAS28-ESR and monthly MCV after starting MTX were obtained. Conventional and machine-learning statistical approaches were applied to the discovery cohort (Cohort 1, 655 patients) and results validated using Cohort 2 (225 patients).
resultsHCQ therapy with MTX was associated with a 2-fold increase in the likelihood of response defined in this study as clinical remission or low disease activity at 6 months (P <0.001). The improved clinical outcome of combination HCQ and MTX therapy was associated with an accelerated rise in MCV from 2 months after commencing therapy. The increase in MCV at 3 months was equivalent to the contemporaneous reduction in the DAS (DAS28-ESR) in predicting clinical response at 6 months. Using latent class mixed modelling, five trajectories of MCV change over 6 months from baseline were identified. The odds ratio of response to treatment was 16.2 (95% CI 5.7, 46.4, P <0.001) in those receiving combination therapy classified within the MCV elevation >5 fl class, which contained the most patients, compared with MTX alone.
conclusionOur data provide mechanistic insight into the synergistic clinical benefit of concomitant HCQ with MTX, boosting the rise in MCV, which could serve as a companion biomarker of treatment response.
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