ABSTRACT Objective Systemic sclerosis (SSc) is a rare autoimmune disease with high mortality, often due to cardiopulmonary complications. Hydroxychloroquine (HCQ), commonly used in other rheumatic diseases, has immunomodulatory and potentially cardioprotective effects, but its role in SSc remains unclear. This study aimed to evaluate the association between HCQ use and the risk of mortality, ischemic heart disease (IHD), and pulmonary hypertension (PH) in a large real‐world SSc cohort. Methods This retrospective cohort study utilized de‐identified electronic medical records from the TriNetX Research network. Adults with an SSc diagnosis (ICD‐10‐CM: M34) were divided into HCQ users and non‐users. After 1:1 propensity score matching for demographics, comorbidities and medications, outcomes including mortality, PH, acute myocardial infarction (MI), cerebral infarction, conduction heart disease, and myocarditis were assessed over 5 years. Risk ratios (RR) and Kaplan–Meier hazard ratios were calculated. Results Out of 17 395 HCQ users and 58 576 non‐users, 15 485 propensity score matched pairs were analyzed. Over 5 years, HCQ users showed higher PH (RR 1.124, 95% CI, 1.052–1.200, p < 0.001) but lower mortality (RR 0.719, 95% CI, 0.674–0.767, p < 0.001), indicating potential survival benefits. No significant differences were observed for IHD, MI, cerebral infarction, conduction disorders, or myocarditis. Conclusion Our research indicated that although patients on HCQ had a higher prevalence of PH, they exhibited lower mortality rates, suggesting a possible survival benefit. Further prospective studies are needed to explore these findings and clarify HCQ's role in SSC management.
Subedi et al. (Sun,) studied this question.