Background/Purpose:

In Japan hydroxychloroquine (HCQ) is still unavailable due to the banning of chloroquine in 1974 following allegations that it caused severe retinopathy. Therefore, a multicenter, double-blind, randomized, parallel-group trial was conducted to develop HCQ on cutaneous lupus erythematosus (CLE) in Japan (NCT01551069).

Methods:

Japanese CLE patients (age≥18) with or without SLE were included. Patients with Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score <4, and fluctuations of CLASI ≥20% in the screening period, administration of prednisolone >15mg/day, and pain VAS or fatigue VAS of 0 in SLE patients were excluded. The study spanned 55 weeks and fell into three phases: the first was the double-blind (HCQ or placebo in a 3:1 ratio for 16 weeks), the second was the single-blind (using HCQ for 36 weeks), and the third was the follow-up phase lasting 3 weeks. This was a baseline-controlled study and placebo was used as a reference. Primary endpoint was a change in CLASI activity score from baseline to 16 weeks. A change in CLASI activity score during the single-blind period was also measured. As secondary endpoints, Skindex29, 7-point scale global assessment (GA) of skin by patient, 5-point scale central photo evaluation, were assessed at Week 16 and, based on them 7-point scale GA of skin was scored by investigator. In SLE cases, the VAS assessment of pain and fatigue, RAPID 3 (Routine assessment of patient index data 3), and focused BILAG index were assessed at Week 16. Safety was assessed up to 55 weeks.

Results:

103 patients were randomized and 72 in HCQ group, 24 in placebo group were analyzed for efficacy. The CLASI score at Week 16 showed significant improvement in both groups (HCQ group: -4.6±6.4, p<0.0001; placebo group: -3.2±4.5, p=0.002). The placebo group experienced further improvement lasting to Week 52 after switching to HCQ, showing a change of -3.3±4.6 compared with -2.1±3.3 for the HCQ group. Skindex29 improved significantly from baseline to 16 weeks in the HCQ group. The percentage of “≥slightly improved” by GA of skin by patient, “≥improved” by central photo evaluation, and “≥improved” by GA of skin by investigator, were 72.9%, 59.4%, and 51.4% in the HCQ group and 47.8%, 30.4%, and 8.7% in the placebo group, respectively. In 56 SLE patients, pain VAS, fatigue VAS, and RAPID3 improved significantly from baseline to 16 weeks in the HCQ group. Active musculoskeletal system (A-C) defined by BILAG improved to be one letter down in 42.1% of the HCQ group at Week 16. Drug eruption, Stevens-Johnson syndrome, hepatic dysfunction, and cellulitis were noted as serious treatment-emergent adverse events related to HCQ treatment. No retinopathy occurred.

Conclusion:

The first clinical trial of HCQ on CLE confirmed the benefits and tolerability of HCQ.

Funding:

Sanofi KK

Japanese Hydroxychloroquine Study Group: Yokogawa N (Tokyo Metropolitan Tama Medical Center, Rheumatology), Furukawa F (Wakayama Medical University, Dermatology), Eto H (St. Luke’s International Hospital, Dermatology), Tanikawa A (Keio University School of Medicine, Dermatology), Ikeda T (Wakayama Medical University, Dermatology), Yamamoto K (The University of Tokyo, Allergy and Rheumatology)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-double-blind-randomized-parallel-group-study-of-hydroxychloroquine-on-cutaneous-lupus-erythematosus-in-japan/