The role of nemolizumab in the treatment of atopic dermatitis for the adult population

Abstract

Atopic dermatitis (AD) often requires long-term treatment that may be associated with adverse effects. This review aims to characterize nemolizumab as a treatment for AD in adults. A literature search was performed to assess nemolizumab's role in moderate-to-severe AD in adults. Currently, clinical trials are being conducted to evaluate the clinical efficacy, safety profile and optimal dosing of nemolizumab for adults with moderate-to-severe AD. The most common adverse effects include nasopharyngitis, AD exacerbation and increased blood creatinine phosphokinase. Recent data from clinical trials suggest nemolizumab may be an acceptable treatment in adults with moderate-to-severe AD.

Plain language summary

Atopic dermatitis, also known as eczema, is a long-lasting skin condition that is difficult to treat. Symptoms include itching, redness, dryness and pain. Various eczema treatments are available to help patients based on how severe their symptoms are. Nemolizumab is a treatment that blocks immune system pathways involving itching and inflammation. This review describes nemolizumab as a treatment option for moderate-to-severe eczema in adults. We completed a literature search to understand nemolizumab's role in eczema treatment. Nemolizumab has decreased itchiness in adults with moderate-to-severe eczema in clinical trials. The most common side effects of nemolizumab treatment were the common cold, worsening of eczema and an increased muscle marker (creatinine phosphokinase). Nemolizumab appears to be an effective treatment for moderate-to-severe eczema in adults with bearable side effects.

Article highlights

Introduction

• AD is a common inflammatory chronic skin disease with a prevalence of 7–11% in adults.

• There are limited effective long-term treatment options for moderate-to-severe AD.

Overview of the field

• Treatment of AD varies by disease severity.

• Mild disease is managed with topical treatments and corticosteroids for flare-ups, while moderate-to-severe disease is managed with topical treatments (TCSs and TCIs) in conjunction with systemic treatments (immunosuppressants and phototherapy).

Introducing nemolizumab

• Nemolizumab (CIM331) is a humanized monoclonal antibody against IL-31 receptor A administered subcutaneously.

• IL-31 receptor A is present on many cells, including neurons. Thus, nemolizumab inhibits IL-31 signaling, which relieves pruritus.

• Nemolizumab is approved to treat pruritus in prurigo nodularis, based on positive phase 3 clinical studies.

• Nemolizumab is used to treat pruritus caused by a variety of disorders and has gained approval for moderate-to-severe AD internationally.

Pharmacology of nemolizumab

• Nemolizumab is an Il-31 receptor A blocker. Il-31 belongs to the gp130/Il-6 cytokine family which plays an important role in modulating the skin, nervous and immune systems.

• Blockade of the Il-31 receptor leads to decreased pruritogenic signaling.

Clinical efficacy

• Nemolizumab decreases PVAS and EASI across a variety of doses and schedules.

• Nemolizumab achieves a greater and more rapid improvement of PVAS and EASI in combination with topical treatments in moderate-to-severe disease than topical treatments alone.

Safety & tolerability

• AEs associated with nemolizumab are primarily mild, with minimal severe AE cases reported.

• Nemolizumab does not increase the incidence of AEs compared with placebo.

• The most common side effects seen are AD exacerbation, nasopharyngitis and increased creatinine phosphokinase.

• Nemolizumab seems to be well tolerated in adults with moderate-to-severe AD.

Regulatory affairs

• The FDA granted nemolizumab Priority Review, as Breakthrough Therapy for PN use.

• The FDA and EMA approved the Biologics License Applications and Marketing Authorization Applications, for nemolizumab treatment of both conditions, AD and PN.

Discussion/future perspective

• Phase 3 nemolizumab clinical trials are currently being performed to understand efficacy and characterize the safety profile of short- and long-term management of moderate-to-severe AD in adults 12 years and older.

• Nemolizumab's distinct inhibition of IL-31 may be beneficial in adults with inadequately managed AD, or resistant to current immunotherapies.

• Head-to-head studies are needed to compare nemolizumab to FDA-approved systemic therapies in moderate-to-severe AD.

Conclusion

• Nemolizumab is an antibody against IL-31 receptor A targeting a pruritus specific pathway.

• Clinical studies suggest nemolizumab can be a safe, well-tolerated, effective alternative management for adults with moderate-to-severe AD.

• Further positive data in future clinical studies may promote FDA approval of nemolizumab in moderate-to-severe AD, with its inhibition of IL-31 signaling.

Keywords: :

• atopic dermatitis
• eczema
• IL-31
• immunotherapy
• pruritus
• systemic treatment

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/1750743X.2024.2383554

Author contributions

S Prajapati – conceptualization, data curation, writing original draft, review & editing. JP Flemming – data curation. D Khan – data curation

H Han – review & editing. B How – review & editing. SS Rozenberg – review & editing. SR Feldman – conceptualization, supervision, review & editing.

Financial disclosure

SR Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, BMS, Ono, Micreos, Eurofins, Informa, UpToDate and the National Psoriasis Foundation. He is founder and part owner of Causa Research and holds stock in Sensal Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.