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Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis.

Abstract Background 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. Methods 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. Results 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. Conclusions 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 .).
PMID
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The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study.

Authors

Mayor MeshTerms
Keywords
Journal Title the new england journal of medicine
Publication Year Start




PMID- 28249150
OWN - NLM
STAT- MEDLINE
DA  - 20170301
DCOM- 20170310
LR  - 20170310
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 376
IP  - 9
DP  - 2017 Mar 02
TI  - Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis.
PG  - 826-835
LID - 10.1056/NEJMoa1606490 [doi]
AB  - Background 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. Methods 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. Results 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&lt;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. 
      Conclusions 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 .).
FAU - Ruzicka, Thomas
AU  - Ruzicka T
AD  - 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.).
FAU - Hanifin, Jon M
AU  - Hanifin JM
AD  - 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.).
FAU - Furue, Masutaka
AU  - Furue M
AD  - 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.).
FAU - Pulka, Grazyna
AU  - Pulka G
AD  - 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.).
FAU - Mlynarczyk, Izabela
AU  - Mlynarczyk I
AD  - 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.).
FAU - Wollenberg, Andreas
AU  - Wollenberg A
AD  - 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.).
FAU - Galus, Ryszard
AU  - Galus R
AD  - 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.).
FAU - Etoh, Takafumi
AU  - Etoh T
AD  - 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.).
FAU - Mihara, Ryosuke
AU  - Mihara R
AD  - 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.).
FAU - Yoshida, Hiroki
AU  - Yoshida H
AD  - 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.).
FAU - Stewart, Jonathan
AU  - Stewart J
AD  - 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.).
FAU - Kabashima, Kenji
AU  - Kabashima K
AD  - 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.).
CN  - XCIMA Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT01986933
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (CIM331)
RN  - 0 (IL31RA protein, human)
RN  - 0 (Receptors, Interleukin)
SB  - AIM
SB  - IM
CIN - N Engl J Med. 2017 Mar 2;376(9):878-879. PMID: 28249132
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*administration &amp; dosage/adverse effects
MH  - Dermatitis, Atopic/*drug therapy
MH  - Edema/chemically induced
MH  - Female
MH  - Humans
MH  - Intention to Treat Analysis
MH  - Male
MH  - Middle Aged
MH  - Pruritus/drug therapy
MH  - Receptors, Interleukin/*antagonists &amp; inhibitors/immunology
IR  - Augustin M
FIR - Augustin, Matthias
IR  - Beissert S
FIR - Beissert, Stefan
IR  - Bewley A
FIR - Bewley, Anthony
IR  - Bukhalo M
FIR - Bukhalo, Michael
IR  - Datta-Adamczak M
FIR - Datta-Adamczak, Magdalena
IR  - Etoh T
FIR - Etoh, Takafumi
IR  - Foelster-Holst R
FIR - Foelster-Holst, Regina
IR  - Fowler J
FIR - Fowler, Joseph
IR  - Fretzin S
FIR - Fretzin, Scott
IR  - Galus R
FIR - Galus, Ryszard
IR  - Grzeszczak I
FIR - Grzeszczak, Iwona
IR  - Hampton M
FIR - Hampton, Marta
IR  - Hata T
FIR - Hata, Tissa
IR  - Haynes S
FIR - Haynes, Stacy
IR  - Hearn R
FIR - Hearn, Robert
IR  - Hide M
FIR - Hide, Michihiro
IR  - Igarashi A
FIR - Igarashi, Atsuyuki
IR  - Imafuku S
FIR - Imafuku, Shinichi
IR  - Inoue T
FIR - Inoue, Tae
IR  - Ishiji T
FIR - Ishiji, Takaoki
IR  - Jones T
FIR - Jones, Terry
IR  - Kawachi Y
FIR - Kawachi, Yasuhiro
IR  - Kawada A
FIR - Kawada, Akira
IR  - Kawashima M
FIR - Kawashima, Makoto
IR  - Kircik L
FIR - Kircik, Leon
IR  - Kolodziej T
FIR - Kolodziej, Tomasz
IR  - Komine M
FIR - Komine, Mayumi
IR  - Korman N
FIR - Korman, Neil
IR  - Krolikowska E
FIR - Krolikowska, Elzbieta
IR  - Martin-Clavijo A
FIR - Martin-Clavijo, Agustin
IR  - McElgunn P
FIR - McElgunn, Patrick
IR  - Mitsui H
FIR - Mitsui, Hiroshi
IR  - Mlynarczyk I
FIR - Mlynarczyk, Izabela
IR  - Murota H
FIR - Murota, Hiroyuki
IR  - Nakahara T
FIR - Nakahara, Takeshi
IR  - Neimann A
FIR - Neimann, Andrea
IR  - Nemoto O
FIR - Nemoto, Osamu
IR  - Pariser D
FIR - Pariser, David
IR  - Pedrozo A
FIR - Pedrozo, Alejandro
IR  - Pinter A
FIR - Pinter, Andreas
IR  - Pulka G
FIR - Pulka, Grazyna
IR  - Schaekel K
FIR - Schaekel, Knut
IR  - Simpson E
FIR - Simpson, Eric
IR  - Slugocki R
FIR - Slugocki, Rafal
IR  - Staubach-Renz P
FIR - Staubach-Renz, Petra
IR  - Sugaya M
FIR - Sugaya, Makoto
IR  - Thaci D
FIR - Thaci, Diamant
IR  - Tharp M
FIR - Tharp, Michael
IR  - Thiers B
FIR - Thiers, Bruce
IR  - Tsianakas A
FIR - Tsianakas, Athanasios
IR  - Urabe K
FIR - Urabe, Kazunori
IR  - Wachsmuth R
FIR - Wachsmuth, Rachel
IR  - Watanabe K
FIR - Watanabe, Ken
IR  - Weglowska J
FIR - Weglowska, Jolanta
IR  - Wollenberg A
FIR - Wollenberg, Andreas
IR  - Worm M
FIR - Worm, Margitta
IR  - Zebrowska A
FIR - Zebrowska, Agnieszka
EDAT- 2017/03/02 06:00
MHDA- 2017/03/11 06:00
CRDT- 2017/03/02 06:00
AID - 10.1056/NEJMoa1606490 [doi]
PST - ppublish
SO  - N Engl J Med. 2017 Mar 2;376(9):826-835. doi: 10.1056/NEJMoa1606490.

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