Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus

doi:10.1016/j.jaci.2019.08.013

Journal of Allergy and Clinical Immunology

Volume 145, Issue 1, January 2020, Pages 173-182

https://doi.org/10.1016/j.jaci.2019.08.013 Get rights and content

Under a Creative Commons license

open access

Background

Nemolizumab targets the IL-31 receptor α subunit involved in atopic dermatitis (AD) pathogenesis.

Objective

We sought to evaluate a new dosing strategy of nemolizumab in patients with AD.

Methods

We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90 mg) subcutaneous injections every 4 weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control with topical treatment (n = 226). The Eczema Area and Severity Index (EASI), the peak pruritus (PP) numeric rating scale (NRS), and the Investigator's Global Assessment (IGA) were assessed. Standard safety assessments were performed.

Results

Nemolizumab improved EASI, IGA, and/or NRS-itch scores, with the 30-mg dose being most effective. Nemolizumab (30 mg) reduced EASI scores versus placebo at week 24 (−68.8% vs −52.1%, P = .016); significant differences were observed by week 8 (P ≤ .01). With significant improvement (P = .028) as early as week 4, IGA 0/1 rates were higher for 30 mg of nemolizumab versus placebo at week 16 (33.3% vs 12.3%, P = .008) but not week 24 because of an increased placebo/topical corticosteroid effect (36.8% vs 21.1%, P = .06). PP-NRS scores were improved for 30 mg of nemolizumab versus placebo at week 16 (−68.6% vs −34.3%, P < .0001) and week 24 (−67.3% vs −35.8%, P < .0001), with a difference by week 1 (P < .001). NRS response rates (≥4-point decrease) were greater for 30 mg of nemolizumab versus placebo at week 16 (P ≤ .001) and week 24 (P ≤ .01). Nemolizumab was safe and well tolerated. The most common adverse events were nasopharyngitis and upper respiratory tract infection.

Conclusions

Nemolizumab resulted in rapid and sustained improvements in cutaneous signs of inflammation and pruritus in patients with AD, with maximal efficacy observed at 30 mg. Nemolizumab had an acceptable safety profile.

Key words

Atopic dermatitis

humanized mAb

anti–IL-31 receptor

Abbreviations used

Atopic dermatitis

DLQI

Dermatology Life Quality Index

EASI

Eczema Area and Severity Index

EASI50

Greater than 50% improvement in EASI score

EASI75

Greater than 75% improvement in EASI score

EASI90

Greater than 90% improvement in EASI score

EQ5D

EuroQoL 5-Dimension

HADS

Hospital Anxiety and Depression Scale

IGA

Investigator's Global Assessment

ITT

Intent to treat

Least square

NRS

Numeric rating scale

Peak pruritis

TCS

Topical corticosteroid

TEAE

Treatment-emergent adverse event

Cited by (0)

: The study was funded by Nestlé Skin Health-Galderma R&D. The funders participated in the conception and design of the study, analysis and interpretation of the data, and drafting and critical revision of the report and provided approval to submit.

: Disclosure of potential conflict of interest: J. I. Silverberg has received honoraria as a speaker/consultant for Galderma, Abbvie, AnaptysBio, Asana, Arena, Boehringer Ingelheim, Dermavant, Eli Lilly, GlaxoSmithKline, Glenmark, Kiniksa, Leo, Menlo, Novartis, Pfizer, Regeneron-Sanofi, and Realm and has received grants as an investigator from Galderma and GlaxoSmithKline. A. Pinter has received compensation as an investigator, speaker, or advisor from AbbVie, Allmirall-Hermal, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Eli Lilly, Galderma, Hexal, Janssen, LEO Pharma, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pfizer, Tigercat Pharma, Regeneron, Roche, Sanofi Aventis, Sandoz Biopharmaceuticals, Schering-Plous, and UCB Pharma. Y. Poulin has received grants as an investigator for Galderma, Abbvie, Amgen, AnaptysBio, Boehringer Ingelheim, Bond Avillion, Celgene, Devonian, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Merck Serono, Pfizer, and UCB Pharma. A. Wollenberg has received grants, personal fees, and/or nonfinancial support from Almirall, Beiersdorf, Bioderma, Chugai, Galapagos, Galderma, Hans Karrer, Leo Pharma, Eli Lilly, L'Oreal, Maruho, MedImmune, Novartis, Pfizer, Pierre Fabre, Regeneron, Santen, and Sanofi-Aventis. D. F. Murrell has received grants as investigator and honoraria as advisor for Galderma, Sanofi, Anacor, Pfizer, Menlo, Pierre Fabre, and GlaxoSmithKline and has also served as an investigator for Regeneron and Medimmune. A. Alexis has served as an investigator and consultant for Galderma, Leo, Novartis, Almirall, Celgene, and Rxl; as an investigator for Bristol-Myers Squibb, Menlo, and SkinMedica; and as a consultant for Pfizer, Sanofi-Regeneron, Trevi, Dermavent, Unilever, BioPharmX, Cipla, Beiersdorf, Valeant, L'Oreal, and P&G. L. Lindsey, F. Ahmad, C. Piketty, and A. Clucas are or were employees of Galderma at the time of the study. The rest of the authors declare that they have no relevant conflicts of interest.

: Clinicaltrials.gov trial registration no. NCT03100344 and EUDRACT no. 2016-005025-37.