title: Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis.
abstract: Interleukin-31 may play a role in the pathobiologic mechanism of atopic dermatitis and pruritus. We wanted to assess the efficacy and safety of nemolizumab (CIM331), a humanized antibody against interleukin-31 receptor A, in the treatment of atopic dermatitis.
  
  
  
  In this phase 2, randomized, double-blind, placebo-controlled, 12-week trial, we assigned adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments to receive subcutaneous nemolizumab (at a dose of 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight) or placebo every 4 weeks or an exploratory dose of 2.0 mg of nemolizumab per kilogram every 8 weeks. The primary end point was the percentage improvement from baseline in the score on the pruritus visual-analogue scale (on which a negative change indicates improvement) at week 12. Secondary end points included changes in the score on the Eczema Area and Severity Index (EASI, on which a negative change indicates improvement), and body-surface area of atopic dermatitis.
  
  
  
  Of 264 patients who underwent randomization, 216 (82%) completed the study. At week 12, among the patients who received nemolizumab every 4 weeks, changes on the pruritus visual-analogue scale were -43.7% in the 0.1-mg group, -59.8% in the 0.5-mg group, and -63.1% in the 2.0-mg group, versus -20.9% in the placebo group (P<0.01 for all comparisons). Changes on the EASI were -23.0%, -42.3%, and -40.9%, respectively, in the nemolizumab groups, versus -26.6% in the placebo group. Respective changes in body-surface area affected by atopic dermatitis were -7.5%, -20.0%, and -19.4% with nemolizumab, versus -15.7% with placebo. Among the patients receiving nemolizumab every 4 weeks, treatment discontinuations occurred in 9 of 53 patients (17%) in the 0.1-mg group, in 9 of 54 (17%) in the 0.5-mg group, and in 7 of 52 (13%) in the 2.0-mg group, versus in 9 of 53 (17%) in the placebo group.
  
  
  
  In this phase 2 trial, nemolizumab at all monthly doses significantly improved pruritus in patients with moderate-to-severe atopic dermatitis, which showed the efficacy of targeting interleukin-31 receptor A. The limited size and length of the trial preclude conclusions regarding adverse events. (Funded by Chugai Pharmaceutical; XCIMA ClinicalTrials.gov number, NCT01986933 .).
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Jon M
authors.initials: JM
authors.lastname: Hanifin
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Grazyna
authors.initials: G
authors.lastname: Pulka
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Izabela
authors.initials: I
authors.lastname: Mlynarczyk
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Wollenberg
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Ryszard
authors.initials: R
authors.lastname: Galus
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Takafumi
authors.initials: T
authors.lastname: Etoh
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Mihara
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stewart
authors.affiliation: From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D004487:Edema / Q000139:chemically induced; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D011537:Pruritus / Q000188:drug therapy; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C502188:IL31RA protein, human; D018123:Receptors, Interleukin; C000612881:nemolizumab