Abstract Objectives Antimalarial agents, particularly hydroxychloroquine, are fundamental in SLE management. While their renal benefits in lupus nephritis (LN) are recognized, their corresponding role in reducing extra-renal damage is less defined. This study examined the association between antimalarial use and extra-renal damage accrual in biopsy-confirmed LN. Methods This was a retrospective analysis of a prospectively followed cohort of patients with biopsy-confirmed LN enrolled in the University of Toronto Lupus Clinic (1970–2024). Extra-renal damage was defined as any increase (≥1) in the extra-renal SLICC/ACR Damage Index (SDI). Antimalarial use was analyzed as a time-dependent variable. Associations were assessed using multivariable Cox proportional hazards models. Results Among 352 patients, the median age was 34.1 years, 14.5% were male, and the median follow-up was 9.6 years IQR 4.9–16.6. Antimalarials were used by 47.7% at baseline, 58.5% during the first year, and 67.9% by year 5. Among 327 patients with complete SDI data, extra-renal damage occurred in 151 patients (46.2%) with a median time of 4.1 years 1.8–8.9. In multivariable models, antimalarial use was independently protective against extra-renal damage accrual (HR 0.51, 95% CI 0.37–0.72). This protective effect remained significant across all baseline extra-renal SDI subgroups, including in patients with SDI=0 and those with SDI ≥1. Conclusions Extra-renal damage is common in patients with LN. In this population, antimalarial therapy was associated with a significant protective effect against extra-renal damage. These findings extend the benefits of antimalarials beyond renal protection and reinforce their essential role in reducing damage accrual in SLE patients with LN.
Kharouf et al. (Thu,) studied this question.