Threshold of Hydroxychloroquine Dose Reduction Associated with Flare in Quiescent Systemic Lupus Erythematosus
Phongpon Sumangin, Sumapa Chaiamnuay, Pongthorn Narongroeknawin, Paijit Asavatanabodee, Pornsawan Leosuthamas, Thunyawarin Arunthanachaikul, Rattapol PakchotanonBackground 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.