INTRODUCTION
Chronic pruritus remains one of the most challenging symptoms to manage across dermatologic and systemic conditions, significantly impairing quality of life and often proving refractory to conventional therapies. Nemolizumab represents a paradigm shift in treating chronic pruritic conditions through its targeted blockade of interleukin-31 (IL-31) receptor α signaling. IL-31, predominantly secreted by Th2 cells, type 2 innate lymphoid cells, and various immune effector cells, has emerged as a critical mediator in the pathophysiology of chronic itch across multiple disease states.1
Four pivotal phase 3 trials have studied nemolizumab in these conditions. The ARCADIA 1 and 2 phase 3 trials enrolled 1,728 patients, 12 years and older with moderate-to-severe atopic dermatitis (AD). Patients were randomly assigned (2:1 ratio) to receive nemolizumab 30 mg subcutaneously every 4 weeks (Q4W) with a loading dose of 60 mg at baseline or placebo, both combined with topical corticosteroids (with or without calcineurin inhibitors) over a 16-week initial period. Both trials met their coprimary endpoints of Investigator's Global Assessment success and Eczema Area and Severity Index 75, with significant pruritus improvement observed as early as week 1 and sleep improvement by week 16.1
The phase 3 OLYMPIA 1 and 2 trials evaluated nemolizumab in a total of 560 adults with moderate-to-severe prurigo nodularis (PN). Both trials demonstrated significant improvements in primary and secondary endpoints, including rapid reduction in itch and sleep disturbance by week 4.2 In OLYMPIA 2, which included 274 patients, 41.0% of those treated with nemolizumab achieved an itch response compared with 7.7% in the placebo group by week 4.
While nemolizumab has secured regulatory approval for AD and PN in patients 12 years and older, clinicians have begun exploring its utility in other IL-31-mediated pruritic conditions. This narrative review synthesizes the emerging evidence on off-label applications of nemolizumab, examining efficacy patterns, safety considerations, and mechanistic insights across diverse pruritic conditions to inform clinical decision-making and identify priorities for future investigation.
Four pivotal phase 3 trials have studied nemolizumab in these conditions. The ARCADIA 1 and 2 phase 3 trials enrolled 1,728 patients, 12 years and older with moderate-to-severe atopic dermatitis (AD). Patients were randomly assigned (2:1 ratio) to receive nemolizumab 30 mg subcutaneously every 4 weeks (Q4W) with a loading dose of 60 mg at baseline or placebo, both combined with topical corticosteroids (with or without calcineurin inhibitors) over a 16-week initial period. Both trials met their coprimary endpoints of Investigator's Global Assessment success and Eczema Area and Severity Index 75, with significant pruritus improvement observed as early as week 1 and sleep improvement by week 16.1
The phase 3 OLYMPIA 1 and 2 trials evaluated nemolizumab in a total of 560 adults with moderate-to-severe prurigo nodularis (PN). Both trials demonstrated significant improvements in primary and secondary endpoints, including rapid reduction in itch and sleep disturbance by week 4.2 In OLYMPIA 2, which included 274 patients, 41.0% of those treated with nemolizumab achieved an itch response compared with 7.7% in the placebo group by week 4.
While nemolizumab has secured regulatory approval for AD and PN in patients 12 years and older, clinicians have begun exploring its utility in other IL-31-mediated pruritic conditions. This narrative review synthesizes the emerging evidence on off-label applications of nemolizumab, examining efficacy patterns, safety considerations, and mechanistic insights across diverse pruritic conditions to inform clinical decision-making and identify priorities for future investigation.
MATERIALS AND METHODS
We conducted a narrative review of the literature examining off-label uses of nemolizumab. We searched PubMed, Ovid Embase, and the Cochrane Library for English-language publications from 2021 through 2025 reporting original data on nemolizumab use for conditions other than approved indications (AD or PN in patients aged 12 years or older).
From each included study, we extracted data on study design, patient demographics, treated conditions, dosing protocols, prior therapies, outcome measures, and safety profiles. Our search was limited to English-language publications in major databases, potentially excluding relevant non-English studies and grey literature.
From each included study, we extracted data on study design, patient demographics, treated conditions, dosing protocols, prior therapies, outcome measures, and safety profiles. Our search was limited to English-language publications in major databases, potentially excluding relevant non-English studies and grey literature.
