Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis
Thomas Ruzicka, Jon M Hanifin, Masutaka Furue, Grazyna Pulka, Izabela Mlynarczyk, Andreas Wollenberg, Ryszard Galus, Takafumi Etoh, Ryosuke Mihara, Hiroki Yoshida, Jonathan Stewart, Kenji Kabashima, XCIMA Study Group, Matthias Augustin, Stefan Beissert, Anthony Bewley, Michael Bukhalo, Magdalena Datta-Adamczak, Takafumi Etoh, Regina Foelster-Holst, Joseph Fowler, Scott Fretzin, Ryszard Galus, Iwona Grzeszczak, Marta Hampton, Tissa Hata, Stacy Haynes, Robert Hearn, Michihiro Hide, Atsuyuki Igarashi, Shinichi Imafuku, Tae Inoue, Takaoki Ishiji, Terry Jones, Yasuhiro Kawachi, Akira Kawada, Makoto Kawashima, Leon Kircik, Tomasz Kolodziej, Mayumi Komine, Neil Korman, Elzbieta Krolikowska, Agustin Martin-Clavijo, Patrick McElgunn, Hiroshi Mitsui, Izabela Mlynarczyk, Hiroyuki Murota, Takeshi Nakahara, Andrea Neimann, Osamu Nemoto, David Pariser, Alejandro Pedrozo, Andreas Pinter, Grazyna Pulka, Knut Schaekel, Eric Simpson, Rafal Slugocki, Petra Staubach-Renz, Makoto Sugaya, Diamant Thaci, Michael Tharp, Bruce Thiers, Athanasios Tsianakas, Kazunori Urabe, Rachel Wachsmuth, Ken Watanabe, Jolanta Weglowska, Andreas Wollenberg, Margitta Worm, Agnieszka Zebrowska, Thomas Ruzicka, Jon M Hanifin, Masutaka Furue, Grazyna Pulka, Izabela Mlynarczyk, Andreas Wollenberg, Ryszard Galus, Takafumi Etoh, Ryosuke Mihara, Hiroki Yoshida, Jonathan Stewart, Kenji Kabashima, XCIMA Study Group, Matthias Augustin, Stefan Beissert, Anthony Bewley, Michael Bukhalo, Magdalena Datta-Adamczak, Takafumi Etoh, Regina Foelster-Holst, Joseph Fowler, Scott Fretzin, Ryszard Galus, Iwona Grzeszczak, Marta Hampton, Tissa Hata, Stacy Haynes, Robert Hearn, Michihiro Hide, Atsuyuki Igarashi, Shinichi Imafuku, Tae Inoue, Takaoki Ishiji, Terry Jones, Yasuhiro Kawachi, Akira Kawada, Makoto Kawashima, Leon Kircik, Tomasz Kolodziej, Mayumi Komine, Neil Korman, Elzbieta Krolikowska, Agustin Martin-Clavijo, Patrick McElgunn, Hiroshi Mitsui, Izabela Mlynarczyk, Hiroyuki Murota, Takeshi Nakahara, Andrea Neimann, Osamu Nemoto, David Pariser, Alejandro Pedrozo, Andreas Pinter, Grazyna Pulka, Knut Schaekel, Eric Simpson, Rafal Slugocki, Petra Staubach-Renz, Makoto Sugaya, Diamant Thaci, Michael Tharp, Bruce Thiers, Athanasios Tsianakas, Kazunori Urabe, Rachel Wachsmuth, Ken Watanabe, Jolanta Weglowska, Andreas Wollenberg, Margitta Worm, Agnieszka Zebrowska
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 .).
Source: PubMed