Effects of Hydroxychloroquine in Patients With Cutaneous Lupus Erythematosus: A Multicenter, Double-Blind, Randomized, Parallel-Group Trial

Objective: To assess the efficacy and tolerability of hydroxychloroquine (HCQ) in patients with cutaneous lupus erythematosus (CLE), in a phase III clinical trial conducted in Japan. Methods: We conducted a double-blind, randomized, parallel-group clinical trial. This was a baseline-controlled study, and the group differences were evaluated in an exploratory analysis. A total of 103 patients with active CLE (according to a Cutaneous Lupus Erythematosus Disease Area and Severity Index [CLASI] activity score of ≥4) were included. Patients were randomized 3:1 to receive HCQ or placebo during the 16-week double-blind period, and all patients were given HCQ during the following 36-week single-blind period. The primary efficacy end point was a reduction in the CLASI activity score at week 16. The secondary end points included the central photo evaluation (5-point scale), patient's global assessment (7-point scale), the Skindex-29 score, and investigator's global assessment (7-point scale, based on the other 3 secondary end points). In patients with systemic lupus erythematosus, fatigue and musculoskeletal pain were assessed. Safety was assessed up to week 55. Results: The mean CLASI score at week 16 was significantly improved from baseline in both the HCQ group and the placebo group: mean change −4.6 (95% confidence interval [95% CI] −6.1, −3.1) (P < 0.0001), and mean change −3.2 (95% CI −5.1, −1.3) (P = 0.002), respectively, without between-group difference (P = 0.197). The investigator's global assessment demonstrated a greater proportion of “improved” and “remarkably improved” patients in the HCQ group (51.4% versus 8.7% in the placebo group [P = 0.0002 between groups]). The other secondary end points supported the efficacy of HCQ. Cellulitis, drug eruption, hepatic dysfunction, and Stevens-Johnson syndrome were shown to be serious adverse events related to HCQ use. Conclusion: The results of this randomized clinical trial support the efficacy and tolerability of HCQ in patients with CLE.