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Publication Detail
The synergistic efficacy of hydroxychloroquine with methotrexate is accompanied by increased erythrocyte mean corpuscular volume.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Shipa MRA, Yeoh S-A, Embleton-Thirsk A, Mukerjee D, Ehrenstein MR
  • Publication date:
  • Pagination:
    787, 793
  • Journal:
    Rheumatology (Oxford)
  • Volume:
  • Issue:
  • Status:
  • Country:
  • PII:
  • Language:
  • Keywords:
    HCQ, MTX, biomarker, mean corpuscular change, synergistic, Antirheumatic Agents, Arthritis, Rheumatoid, Drug Synergism, Drug Therapy, Combination, Erythrocyte Indices, Female, Humans, Hydroxychloroquine, Male, Methotrexate, Middle Aged, Remission Induction, Retrospective Studies
OBJECTIVES: To 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. METHODS: A 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). RESULTS: HCQ 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. CONCLUSION: Our 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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