Comparative outcomes of COVID-19 in patients with primary Sjögren’s syndrome treated with hydroxychloroquine versus methotrexate

Background: People with rheumatic diseases are considered at risk for severe coronavirus disease 2019 (COVID-19) because of their underlying abnormal immune responses and frequent disease-modifying antirheumatic drug (DMARD) use. We aimed to explore COVID-19 outcomes in patients with primary Sjögren’s syndrome (pSS) receiving different conventional synthetic DMARDs. Methods: The study was a retrospective analysis of real data from the TriNetX platform between 1 January 2020 and 30 June 2023. We compared COVID-19 outcomes between cohorts of pSS patients treated with hydroxychloroquine (HCQ) and methotrexate (MTX). Results: After propensity score matching, 1045 and 1045 pSS patients in the HCQ and MTX cohorts were included in the analysis. Our study revealed that the risk of COVID-19 in the HCQ cohort was significantly 25.9% lower than that in the MTX cohort. Among 18–64-year-old patients and unvaccinated patients, those in the HCQ cohort had a significantly lower risk of contracting COVID-19 than did those in the MTX cohort. Regarding the comorbidities of chronic kidney disease and neoplasms, the HCQ cohort had a significantly lower risk of adverse outcomes than the MTX cohort. Conclusions: This is the first study in which a significant number of pSS patients was enrolled and head-to-head to compare the risk of COVID-19 incidence and adverse outcomes between those receiving HCQ and those receiving MTX, and we concluded that the risk of COVID-19 incidence was significantly lower in the HCQ cohort than in the MTX cohort. However, there were no significant differences in adverse COVID-19 outcomes between the cohorts.