Anti-interleukin-31 receptor a antibody for atopic dermatitis

Thomas Ruzicka, Jon Hanifin, Masutaka Furue, Grazyna Pulka, Izabela Mlynarczyk, Andreas Wollenberg, Ryszard Galus, Takafumi Etoh, Ryosuke Mihara, Hiroki Yoshida, Jonathan Stewart, Kenji Kabashima

Research output: Contribution to journalArticle

184 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)826-835
Number of pages10
JournalNew England Journal of Medicine
Volume376
Issue number9
DOIs
StatePublished - Mar 2 2017

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Interleukin Receptors
Atopic Dermatitis
Placebos
Pruritus
Antibodies
Body Surface Area
Visual Analog Scale
Antibodies, Monoclonal, Humanized
Interleukins
Eczema
Random Allocation
Therapeutics
Body Weight
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ruzicka, T., Hanifin, J., Furue, M., Pulka, G., Mlynarczyk, I., Wollenberg, A., ... Kabashima, K. (2017). Anti-interleukin-31 receptor a antibody for atopic dermatitis. New England Journal of Medicine, 376(9), 826-835. https://doi.org/10.1056/NEJMoa1606490

Anti-interleukin-31 receptor a antibody for atopic dermatitis. / Ruzicka, Thomas; Hanifin, Jon; Furue, Masutaka; Pulka, Grazyna; Mlynarczyk, Izabela; Wollenberg, Andreas; Galus, Ryszard; Etoh, Takafumi; Mihara, Ryosuke; Yoshida, Hiroki; Stewart, Jonathan; Kabashima, Kenji.

In: New England Journal of Medicine, Vol. 376, No. 9, 02.03.2017, p. 826-835.

Research output: Contribution to journalArticle

Ruzicka, T, Hanifin, J, Furue, M, Pulka, G, Mlynarczyk, I, Wollenberg, A, Galus, R, Etoh, T, Mihara, R, Yoshida, H, Stewart, J & Kabashima, K 2017, 'Anti-interleukin-31 receptor a antibody for atopic dermatitis', New England Journal of Medicine, vol. 376, no. 9, pp. 826-835. https://doi.org/10.1056/NEJMoa1606490
Ruzicka T, Hanifin J, Furue M, Pulka G, Mlynarczyk I, Wollenberg A et al. Anti-interleukin-31 receptor a antibody for atopic dermatitis. New England Journal of Medicine. 2017 Mar 2;376(9):826-835. https://doi.org/10.1056/NEJMoa1606490
Ruzicka, Thomas ; Hanifin, Jon ; Furue, Masutaka ; Pulka, Grazyna ; Mlynarczyk, Izabela ; Wollenberg, Andreas ; Galus, Ryszard ; Etoh, Takafumi ; Mihara, Ryosuke ; Yoshida, Hiroki ; Stewart, Jonathan ; Kabashima, Kenji. / Anti-interleukin-31 receptor a antibody for atopic dermatitis. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 9. pp. 826-835.
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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.",
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AU - Ruzicka, Thomas

AU - Hanifin, Jon

AU - Furue, Masutaka

AU - Pulka, Grazyna

AU - Mlynarczyk, Izabela

AU - Wollenberg, Andreas

AU - Galus, Ryszard

AU - Etoh, Takafumi

AU - Mihara, Ryosuke

AU - Yoshida, Hiroki

AU - Stewart, Jonathan

AU - Kabashima, Kenji

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N2 - 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.

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<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.

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