Threshold of Hydroxychloroquine Dose Reduction Associated with Flare in Quiescent Systemic Lupus Erythematosus

BACKGROUND AND OBJECTIVES: Hydroxychloroquine (HCQ) is recommended for nearly all patients with systemic lupus erythematosus (SLE) unless contraindicated. However, concerns regarding long-term toxicity have led to increasing consideration of HCQ dose reduction or discontinuation. The threshold of HCQ dose reduction in clinically quiescent SLE remain unclear. METHODS: This retrospective cohort included 381 patients with SLE in clinical remission (cSLEDAI-2K=0, prednisolone ≤5 mg/day, ongoing HCQ). The primary outcome was SLE flare, defined as ≥1-point increase in clinical SLEDAI-2K or treatment escalation. HCQ dose reduction during follow-up was evaluated using adjusted Cox proportional hazards models (aHR) for time-to-flare and adjusted logistic regression for flare occurrence (aOR). Receiver operating characteristic (ROC) analysis identified the reduction threshold. RESULTS: Over a median follow-up of 1.38 years, 52.5% developed flares. HCQ discontinuation was associated with increased flare risk (aHR 1.80, 95% CI 1.17-2.75; aOR 5.60, 95% CI 2.47-12.71). A ≥75% reduction was similarly associated with higher flare risk (aHR 1.53, 95% CI 1.02-2.30; aOR 4.40, 95% CI 2.17-8.92), whereas lesser reductions were not. Each 10% dose reduction showed a dose-response relationship in logistic analysis (aOR 1.13, 95% CI 1.06-1.21). ROC analysis identified a 74.7% reduction as an exploratory threshold for HCQ dose reduction (AUC 0.55). CONCLUSIONS: In clinically quiescent SLE, HCQ discontinuation and substantial dose reduction (≥75%) are associated with increased flare risk. These findings support cautious HCQ tapering and avoidance of marked dose reduction.