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

To determine whether concomitant hydroxychloroquine modulates the increase in erythrocyte mean corpuscular volume (MCV) caused by methotrexate therapy, and whether this is associated with improved clinical response in rheumatoid arthritis (RA).A retrospective observational analysis was conducted on two independent hospital datasets of biologic-naïve, early-RA patients who started oral methotrexate. Baseline characteristics, DAS28-ESR and monthly MCV after starting methotrexate 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).Hydroxychloroquine therapy with methotrexate was associated with a two-fold increase in the likelihood of response defined in this study as clinical remission or low disease activity at 6 months (p  <0.001) in those receiving combination therapy classified within the MCV elevation >5fL class, which contained the most patients, compared to methotrexate alone.Our data provides mechanistic insight into the synergistic clinical benefit of concomitant hydroxychloroquine with methotrexate, boosting the rise in MCV which could serve as a companion biomarker of treatment response.

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Authors: Muhammad Ruhu Amin Shipa, Su-Ann Yeoh, Andrew Embleton-Thirsk, Dev Mukerjee, Michael R Ehrenstein