[Hydroxychloroquine in systemic lupus erythematosus: Key updates].

Abstract

Hydroxychloroquine (HCQ) is a cornerstone treatment for systemic lupus erythematosus (SLE). Despite its long-standing use, recent studies have refined recommendations on dosage, toxicity, adherence, and benefits. The 2023 EULAR and 2024 KDIGO guidelines recommend a dose of 5mg/kg/day, with adjustments for renal impairment. However, reducing HCQ dose to≤5mg/kg/day increases the risk of moderate-to-severe flares (OR=6.04 [1.71-21.3]) and lupus-related hospitalizations (aOR=4.2 [1.45-12.19]). The prevalence of HCQ-related retinopathy reaches 8.6-11.5% after 15 years of use. Established risk factors include high daily doses, prolonged treatment, renal impairment, tamoxifen use, and pre-existing maculopathy. Recent studies have identified additional risks, including female sex (HR=3.83 [95% CI, 1.86-7.89]), darker skin phototypes (OR=5.5 [1.4-26.5]), serotonin-norepinephrine reuptake inhibitors (OR=6.6 [1.2-40.9]), an [HCQ]/[DCQ] ratio<7.2 (OR=8.4 [2.7-30.8]), and antiphospholipid syndrome (OR=8.9 [2.2-41.4]). The 2024 PNDS recommends annual ophthalmologic screening after five years of treatment. HCQ withdrawal significantly increases relapse risk, with severe flares occurring up to six times more frequently. A study on patients discontinuing HCQ due to retinopathy found a higher relapse rate compared to adherent patients (31.3 vs. 12.5%, OR=3.1 [1.2-8.2]). An algorithm for interpreting HCQ blood levels has been proposed, identifying levels below 200ng/mL as markers of poor adherence, correlating with an 80% missed-dose rate. Moreover, several studies confirm that HCQ is safe during pregnancy and does not increase the risk of congenital malformations. Finally, HCQ has been associated with a reduced risk of cardiovascular events in SLE. A study involving 52,883 patients found that HCQ use significantly lowered the incidence of cardiovascular events (OR=0.63 [0.57-0.69]). Recent evidence reinforces HCQ's essential role in SLE. Careful dose management, adherence monitoring, and ophthalmologic screening are crucial for optimizing treatment outcomes.