UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

The synergistic efficacy of hydroxychloroquine with methotrexate is accompanied by increased erythrocyte mean corpuscular volume

Ehrenstein, M; Shipa, M; Yeoh, S-A; Embleton-Thirsk, A; Mukerjee, D; (2021) The synergistic efficacy of hydroxychloroquine with methotrexate is accompanied by increased erythrocyte mean corpuscular volume. Rheumatology , 61 (2) pp. 787-793. 10.1093/rheumatology/keab403. Green open access

[thumbnail of Ehrenstein_keab403.pdf]
Preview
Text
Ehrenstein_keab403.pdf

Download (717kB) | Preview

Abstract

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.

Type: Article
Title: The synergistic efficacy of hydroxychloroquine with methotrexate is accompanied by increased erythrocyte mean corpuscular volume
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/rheumatology/keab403
Publisher version: https://doi.org/10.1093/rheumatology/keab403
Language: English
Additional information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: MTX, HCQ, mean corpuscular change, biomarker, synergistic
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > Comprehensive CTU at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10126931
Downloads since deposit
8Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item