Cutaneous Manifestations Associated with Nemolizumab

In the 2025 study by Sasaki et al entitled “Clinical characteristics and risk factors for cutaneous manifestations associated with nemolizumab in atopic dermatitis: a multicenter retrospective study in Japan,” nemolizumab-induced cutaneous eruptions were found to be relatively common, typically occurred early on in treatment, and appeared independent of baseline disease severity or biomarkers in patients with atopic dermatitis (AD).¹

Background and Study Results

Nemolizumab is an anti-IL-31 receptor A antibody approved for treating AD-associated pruritus in Japan in 2022.²  Despite its efficacy in reducing pruritus, studies have reported the presence of cutaneous manifestations associated with nemolizumab that differ morphologically and clinically from exacerbations of baseline AD.^3,4,5  In this 2025 retrospective study, Japanese researchers conducted a multi-center retrospective study to determine the clinical characteristics and incidence of nemolizumab-associated cutaneous manifestations and assess potential correlations between eruption occurrence, baseline disease severity, and immunological factors. Their findings expanded the current understanding, evaluation, and management of nemolizumab-induced cutaneous symptoms. 

The study included 219 participants ages 13 and older with AD who were treated with at least one dose of nemolizumab between August 2022 and February 2024. Of these, 88 patients (40.2%) developed nemolizumab-induced cutaneous manifestations; 80% of these eruptions occurred within the first 3 doses. Eruptions were classified into 6 distinct categories. Erythema was most commonly reported (69.3%) and occurred primarily within the first 3 doses, followed by coin-shaped plaques with exudates, which arose after the second dose. The most common sites of initial eruptions were the forearms, back, upper arms, and lower legs. 

Among patients who developed cutaneous symptoms, 58% were able to continue nemolizumab treatment with the use of high-potency topical corticosteroids, while 42% discontinued therapy. Notably, median eruption duration did not differ significantly between those who continued treatment (27 days) and those who discontinued (33 days). More than 60% of eruptions were non-pruritic and there was no statistically significant association between risk of cutaneous eruptions, age group, baseline disease severity, prior systemic treatments, type 2 inflammatory markers, comorbid allergic conditions, and presence of prurigo nodularis. 

Comments and Clinical Implications

This study demonstrated that nemolizumab-induced cutaneous eruptions were relatively common, present early during treatment, and not significantly associated with demographic and clinical characteristics, baseline severity, or immunological factors. This raises several important clinical implications. Recognizing the timing of eruption onset helps clinicians anticipate when reactions are most likely to occur, allowing for early identification of manifestations, timely treatment with topical therapy, and closer monitoring during the first 3 doses. Mild eruptions can often be managed with topical corticosteroids, while severe cutaneous reactions may result in cessation of therapy. 

Patients who discontinue nemolizumab should be counseled on delayed symptom resolution and encouraged to adhere to topical regimens. No patient characteristics predictive of higher cutaneous eruption risk were identified. This may have been due in part to the retrospective design of the study. Changes in biomarkers or skin conditions could not be tracked over time, limiting insight into the development, progression, and resolution of these adverse events. Given this limitation, this study alone cannot rule out the existence of predisposing risk factors. 

Another important limitation is that the dosing of nemolizumab in Japan is higher than the approved dosing for AD in the United States: 60 mg every 4 weeks vs 60 mg loading dose followed by 30 mg every 4 weeks until week 16, at which point every 8 week dosing may be initiated. Thus, further prospective studies (ideally with both dosing regimens) to identify immunological or genetic markers that may increase a patient’s risk of developing nemolizumab-induced cutaneous manifestations are needed. 

1. Sasaki W, Saito R, Suzuki K, et al. Clinical characteristics and risk factors for cutaneous manifestations associated with nemolizumab in atopic dermatitis: a multicenter retrospective study in Japan. J Dermatol. Published online July 23, 2025. http://doi:10.1111/1346-8138.17877

2. Saeki H, Akiyama M, Abe M, et al. English version of Japanese guidance for biologics in treating atopic dermatitis. J Dermatol. 2023;50(10). http://doi:10.1111/1346-8138.16932

3. Kabashima K, Matsumura T, Komazaki H, Kawashima M. Nemolizumab plus topical agents in patients with atopic dermatitis and moderate to severe pruritus provides improvement in pruritus and signs of AD for up to 68 weeks: results from two phase III, long-term studies. Br J Dermatol. 2021;186(4):642-651. http://doi:10.1111/bjd.20873

4. Masuda T, Yonekura S, Kataoka K, et al. Psoriasis-like lesions in an atopic dermatitis patient possibly associated with nemolizumab treatment. J Dermatol. 2023;51(6). http://doi:10.1111/1346-8138.17085

5. Katsuta M, Kamide R, Ishiuji Y, Nobeyama Y, Asahina A. Bullous pemphigoid that developed during nemolizumab treatment for atopic dermatitis: two case reports. Acta Derm Venereol. 2024;104. http://doi:10.2340/actadv.v104.40634

Peter Lio, MD

• Dermatologist
• Clinical Assistant Professor of Dermatology and Pediatrics
• Northwestern University School of Medicine
  Chicago

 Kelly Duong

• Medical student
• University of Illinois College of Medicine