Background/Purpose: Antimalarials, particularly hydroxychloroquine, are a cornerstone of systemic lupus erythematosus (SLE) management, with well-established benefits including reduced disease activity, prevention of flares, and mitigation of long-term organ damage. We aimed to assess whether antimalarial use is associated with a decreased risk of developing incident lupus nephritis (LN) among patients with SLE.

Methods: We included SLE patients from an inception cohort without prior diagnosis of LN, followed prospectively at regular intervals. The association between antimalarial exposure (measured as cumulative duration in years) and the development of LN (defined by new-onset proteinuria as per SLE Disease Activity Index 2000 [SLEDAI-2K]) was evaluated using a time-dependent univariable Cox proportional hazards model to estimate the overall effect. A time-dependent multivariable Cox regression model adjusted for clinically relevant covariates was also employed to estimate the risk of LN in the full cohort and, in a sensitivity analysis, among patients with serologically active disease. Death was treated as a competing risk.

Results: A total of 674 inception SLE patients were included, with a median baseline age of 33.6 years [IQR: 24.9, 45.4] (Table 1). Over 6,961.5 patient-years of follow-up, 154 patients (22.8%) developed new-onset SLE-related proteinuria, indicating LN, yielding an incidence rate of 2.2 cases per 100 person-years. The median time to LN onset was 3.6 years [IQR: 0.9–8.8]. Cumulative antimalarial exposure was not significantly associated with reduced LN risk, in either the univariable analysis (HR: 0.98; 95% CI: 0.94–1.02, p=0.25) or the adjusted multivariable model (HR: 0.96; 95% CI: 0.92–1.00, p=0.08) (Table 2). Similar results were observed in the sensitivity analysis restricted to patients who presented with serologically active disease (HR: 0.95; 95% CI: 0.89–1.01, p=0.12) (Table 3). Notably, shorter SLE duration (HR: 0.64; 95% CI: 0.58–0.71 per 10-year increase) and higher SLEDAI-2K scores (HR: 1.23; 95% CI: 1.19–1.26) were significantly associated with increased risk of LN (Table 2). This association persisted in patients with serologically active disease, along with glucocorticoid use (Table 3), likely reflecting confounding by indication.

Conclusion: In this inception cohort-based study, antimalarial use was not significantly associated with a reduced risk of incident LN. These findings should be interpreted within the context of the study’s specific objective and are not intended to challenge the well-established role of antimalarials in the management of SLE or their recognized clinical benefits. Further studies with larger sample sizes are needed to confirm our results.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/is-antimalarial-use-associated-with-a-reduced-risk-of-lupus-nephritis-in-patients-with-sle-results-from-an-inception-cohort-based-study/