Risk of flare in patients with SLE in remission after hydroxychloroquine or chloroquine withdrawal

Abstract

Objective: Previous studies have provided evidence that the discontinuation of hydroxychloroquine (HCQ), and chloroquine (CQ), in patients with systemic lupus erythematosus (SLE) is associated with an increased risk of disease flares, with limited information on the level of disease activity at the time of HCQ/CQ discontinuation. Here we aimed to describe the risk of SLE flare after withdrawal of HCQ or CQ in patients with SLE in remission.

Methods: Case-control study (1:2) comparing the evolution of patients with SLE after HCQ/CQ withdrawal for antimalarial retinopathy (cases) with patients with SLE matched for sex, antimalarial treatment duration and age at SLE diagnosis, whose antimalarial treatment was continued throughout the entire follow-up period (controls). To be included in the study, patients had to be in remission for at least one year according to the DORIS classification. The primary endpoint was the proportion of patient experiencing a flare according to the SELENA-SLEDAI Flare Index after a 36-month follow-up.

Results: We studied 48 cases and 96 controls. The proportion of patients experiencing a flare was significantly higher in the HCQ/CQ withdrawal group as compared to the maintenance group (15 [31.3%] patients versus 12 [12.5%]; OR 3.1 [95%CI 1.2-8.2], P=0.01). Withdrawal of HCQ/CQ was inferior with respect to occurrence of severe SLE flare (12 [25.0%] vs 11 [11.5%]; OR 2.5 [95%CI 0.9-6.9], P=0.053) and time to first flare (HR 6.3 [2.0-19.9], P<0.005). Elevated serum levels of anti-dsDNA antibodies were identified as a risk factor for SLE flare following HCQ/CQ discontinuation (HR 5.4 [1.5-18.7], P<0.01).

Conclusion: Withdrawal of HCQ or CQ in patients with SLE in remission is associated with a 3-fold increased risk of relapse.

Keywords: Chloroquine; Hydroxychloroquine; Retinopathy; Systemic lupus erythematosus.