ARTHRITIS & RHEUMATOLOGY Vol. 69, No. 4, April 2017, pp 791–799 DOI 10.1002/art.40018 V C 2016, American College of Rheumatology Effects of Hydroxychloroquine in Patients With Cutaneous Lupus Erythematosus A Multicenter, Double-Blind, Randomized, Parallel-Group Trial N. Yokogawa, 1 H. Eto, 2 A. Tanikawa, 3 T. Ikeda, 4 K. Yamamoto, 5 T. Takahashi, 6 H. Mizukami, 6 T. Sato, 6 N. Yokota, 6 and F. Furukawa 4 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, random- ized, 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 Erythemato- sus 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 sys- temic lupus erythematosus, fatigue and musculoskeletal pain were assessed. Safety was assessed up to week 55. Results. The mean CLASI score at week 16 was sig- nificantly 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 investi- gator’s global assessment demonstrated a greater propor- tion 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 erup- tion, hepatic dysfunction, and Stevens-Johnson syndrome ClinicalTrials.gov identifier: NCT01551069. Supported by Sanofi K.K. 1 N. Yokogawa, MD: Tokyo Metropolitan Tama Medical Cen- ter, Tokyo, Japan; 2 H. Eto, MD, PhD: St. Luke’s International Hospi- tal, Tokyo, Japan; 3 A. Tanikawa, MD, PhD: Keio University School of Medicine, Tokyo, Japan; 4 T. Ikeda, MD, PhD, F. Furukawa, MD, PhD: Wakayama Medical University, Wakayama, Japan; 5 K. Yamamoto, MD, PhD: University of Tokyo, Tokyo, Japan; 6 T. Takahashi, MSc, H. Mizukami, T. Sato, MD, PhD, N. Yokota, MSc: Sanofi K.K., Tokyo, Japan. Drs. Yokogawa, Eto, Tanikawa, Ikeda, Yamamoto, and Furukawa are members of the Japanese Hydroxychloroquine Study Group. Dr. Yokogawa has received consulting fees, speaking fees, and/ or honoraria from AbbVie, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Eli Lilly Japan, and Mitsubishi Tanabe Pharma (less than $10,000 each). Dr. Eto has received speaking fees from Daiichi Sankyo, Eli Lilly, LEO Pharma, Janssen Pharmaceuticals, GlaxoSmithKline, Eisai, Maruho, AbbVie, Mitsubishi Tanabe Pharma, Sumitomo Dainippon Pharma, and JIMRO (less than $10,000 each). Dr. Tanikawa has received consulting fees from Torii Pharmaceutical, GlaxoSmithKline, and Sanofi (less than $10,000 each). Dr. Ikeda has received speaking fees from Chugai Pharmaceutical and Daiichi Sankyo (less than $10,000 each). Dr. Yamamoto has received speaking fees from MSD, Astellas Pharma, AstraZeneca, AbbVie, Abbott, Ayumi Pharmaceutical, Eisai, Toyama Chemical, GlaxoSmithKline, Sanofi, Pfizer, Bristol-Myers Squibb, Janssen Pharmaceuticals, UCB, Asahi Kasei, Santen Pharmaceutical, Ono Pharmaceutical, Taisho Toyama Pharmaceutical, Daiichi Sankyo, Chugai Pharmaceutical, Teijin, Mitsubishi Tanabe Pharma, Eli Lilly, Boehringer Ingelheim, Nippon Kayaku, Nippon Shinyaku, and Takeda Pharmaceutical (less than $10,000 each) and research grants from Takeda Pharmaceutical, Astellas Pharma, Mitsubishi Tanabe Pharma, Teijin, Pfizer, Bristol- Myers Squibb, AbbVie, Sanofi, Eisai, Daiichi Sankyo, Chugai Pharma- ceutical, Santen Pharmaceutical, and Janssen Pharmaceuticals. Dr. Furukawa has received speaking fees from Sanofi, Daiichi Sankyo, GlaxoSmithKline, Maruho, Novartis Pharma, and Kyouwa Hakkou Kirin (less than $10,000 each) and research grants from Sanofi, JMEC, Maruho, Ohtsuka Pharmaceutical, GlaxoSmithKline, Novartis Pharma, Kyouwa Hakkou Kirin, and Mitsubishi Tanabe Pharma. Address correspondence to F. Furukawa, MD, PhD, Depart- ment of Dermatology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan. E-mail: dajs@wakayama-med.ac.jp. Submitted for publication February 29, 2016; accepted in revised form December 6, 2016. 791