Clinical Characteristics and Risk Factors for Cutaneous Manifestations Associated With Nemolizumab in Atopic Dermatitis: A Multicenter Retrospective Study in Japan

Abstract

Nemolizumab, an anti-interleukin-31 receptor A monoclonal antibody, has been approved in Japan for treating atopic dermatitis (AD)-associated pruritus. While it is effective for itch control, nemolizumab-associated cutaneous adverse events have been increasingly recognized, yet their clinical features remain poorly characterized. In this study, we aimed to investigate the incidence, clinical characteristics, and timing of cutaneous manifestations associated with nemolizumab treatment in patients with AD, and to explore potential associations with baseline disease severity and immunological parameters. We conducted a multicenter retrospective study involving 219 patients aged ≥ 13 years with AD who received nemolizumab at 13 institutions in Japan between August 2022 and February 2024. Cutaneous eruptions were classified into six categories based on clinical consensus. Patients who received fewer than three doses without developing skin reactions were excluded. Clinical and laboratory parameters were compared between patients with and without cutaneous manifestations. Cutaneous manifestations occurred in 88 patients (40.2%), most commonly within the first three doses. Erythema was the most frequent presentation (69.3%), and 62.5% of eruptions were non-pruritic. No significant associations were observed between the occurrence of skin reactions and baseline eczema area and severity index scores, eosinophil counts, serum immunoglobulin E, or thymus and activation-regulated chemokine levels. Two cases of bullous pemphigoid were identified. Despite topical corticosteroid treatment, nemolizumab therapy was discontinued in 42% of the patients affected. In conclusion, nemolizumab frequently induces early-onset, morphologically distinct cutaneous eruptions that appear to be independent of baseline disease severity or biomarkers.