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

Abstract

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 baselinecontrolled 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 doubleblind 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 24.6 (95% confidence interval [95% CI] 26.1, 23.1) (P < 0.0001), and mean change 23.2 (95% CI 25.1, 21.3) (P 5 0.002), respectively, without between-group difference (P 5 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 5 0.0002 between groups]). The other secondary end points supported the efficacy of HCQ. Cellulitis, drug eruption, hepatic dysfunction, and Stevens-Johnson syndrome ClinicalTrials.gov identifier: NCT01551069. Supported

Early cutaneous eruptions after oral hydroxychloroquine in a lupus erythematosus patient: A case report and review of the published work

“…It may be a reactive allergic phenomenon associated with an imbalance in the immune system in an early stage after the initiation of HCQ . We summarize the characteristics of 21 reported cases of LE with cutaneous reactions due to HCQ, including our case, in Table . There were 11 cases of SLE (52.38%), eight of CLE (38.1%) and 2 of discoid lupus erythematosus (9.52%).…”

“…Hydroxychloroquine (HCQ) is an antimalarial drug that has been widely used in the treatment of lupus erythematosus (LE) for more than 50 years. Although HCQ is generally tolerated better than other disease‐modifying drugs, it may still cause some adverse effects, including cutaneous toxicities, which lead to its cessation in some patients . After the initiation of this drug, an early adverse cutaneous eruption and an uncontrolled LE‐induced eruption usually share some similarities of symptoms; therefore, it is important to distinguish these two cutaneous eruptions in clinical practise.…”

Hydroxychloroquine enhanced urticarial reaction in a patient with discoid lupus erythematosus

“…The patient who had a history of chronic urticaria also complained about urticarial reaction more frequently 3 weeks later, which was improved with epinastine (10 mg daily) combination. The primary end point was judged by the change in the cutaneous lupus erythematosus disease area and severity index (CLASI) activity score following of HCQ treatment [2][3][4] . The CLASI activity score improved from 11 to 5 for 3 months.…”

“…However, since it is too old drug, there are few scientific evidences and a very small number of mechanisms. A few years ago, we reported a multi-center, double-blind, randomized, parallel-group trial of HCQ in Japanese [2] . Since almost 2 years passed, this case report focused side effects especially urticaria.…”

Hydroxychloroquine in lupus erythematosus, a new horizon of the old drug

“…However, in Japan, HCQ followed the same fate as chloroquine even though there were no clinical experiences. Recently, nationwide clinical trials on the efficacy and safety (multicenter randomized control trial) were performed and excellent results were reported [5] . Interestingly, this report is the first clinical trial oriented for the approval because HCQ is very old and was approved in 1955 in the United States of America.…”