Nemolizumab 30mg powder and solvent for solution for injection pre-filled disposable devices

Nemolizumab is a new biologic approved to treat atopic dermatitis. In this perspective piece, we use results from our living systematic review and network meta-analysis to provide perspective on the relative efficacy of nemolizumab compared with other approved targeted systemic treatments.

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This meta-analysis evaluated the efficacy and safety of nemolizumab in treating prurigo nodularis through a systematic review of randomized controlled trials. A comprehensive literature search was conducted across multiple databases, including PubMed, Embase, Cochrane Library, and Web of Science, identifying relevant studies until January 5th 2025. Four randomized controlled trials involving 859 participants were included in the final analysis. The primary outcomes assessed were itching response measured by the Worst Itch Numeric Rating Scale (WI-NRS) and Investigator's Global Assessment (IGA) success. Nemolizumab demonstrated significant improvement in itch response compared to control, with a risk ratio of 3.52 (95% CI: 2.48 to 5.02, p < 0.00001) and low heterogeneity (I² = 28%). Similarly, IGA success rates were notably higher in the nemolizumab group, with a risk ratio of 4.40 (95% CI: 2.86 to 6.75, p < 0.00001) and low heterogeneity (I² = 11%). While adverse events were slightly more frequent in the nemolizumab group, the difference was not statistically significant (RR: 1.11, 95% CI: 0.99 to 1.24). The analysis was limited by the small number of included trials, relatively short follow-up periods, and lack of subgroup analysis. Despite these limitations, the findings suggest that nemolizumab is an effective and well-tolerated treatment for prurigo nodularis. Further research with longer follow-up periods and larger, more diverse patient populations is recommended to establish the long-term efficacy and safety profile of nemolizumab in treating this condition.

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INTRODUCTION: Atopic dermatitis (AD), with its signs and symptoms of pruritus, dryness, and erythema, severely reduces the quality of life (QOL) of affected patients. We investigated the impact of nemolizumab 60 mg on QOL in Japanese patients aged ≥ 13 years with AD and inadequately controlled moderate-to-severe pruritus, using data derived from patient-reported outcome (PRO) measures. METHODS: PROs were the Insomnia Severity Index (ISI), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), and Work Productivity and Activity Impairment: Atopic Dermatitis questionnaire (WPAI-AD). Correlations between PRO scores and symptom severity, assessed by the pruritus visual analog scale (VAS) and the Eczema Area and Severity Index (EASI), were explored. RESULTS: The mean percent change (standard error) from baseline in the pruritus VAS and EASI scores at week 16 was, respectively, -45.6% (2.7) and -46.0% (3.2) in the nemolizumab group, and -24.1% (3.7) and -33.2% (4.9) in the placebo group. By week 16, significantly more patients in the nemolizumab group versus the placebo group had an ISI score of 0 for difficulty falling asleep (41.6% versus 13.1%, nominal p < 0.01) or difficulty staying asleep (45.4% versus 10.9%; nominal p < 0.01). Similarly, more nemolizumab- than placebo-treated patients had a DLQI score of 0 for interference with shopping, or home/garden activities (45.2% versus 18.6%, nominal p < 0.01), and 0 days per week of nighttime sleep disturbance (50.8% versus 16.9%, nominal p < 0.01) or bleeding skin (43.4% versus 7.5%, nominal p < 0.01) measured by POEM at week 16. Based on WPAI-AD scores, long-term administration of nemolizumab also improved the ability to conduct work activities. CONCLUSIONS: Subcutaneous administration of nemolizumab ameliorated pruritus and skin signs, and thereby produced improvement in patient QOL across multiple PRO measures, including sleep, interpersonal relationships, and the ability to conduct social or work activities. CLINICAL TRIAL REGISTRATION: JapicCTI-173740 (registered 20 October 2017).

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Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, with interleukin (IL)-4, IL-13, and IL-31 recognized as key mediators. Prurigo nodularis (PN) is another chronic inflammatory disorder driven by T helper type 2-mediated inflammation and neural dysregulation, leading to severe pruritus. Nemolizumab, a humanized monoclonal antibody targeting IL-31 receptor A, has been approved for use in the treatment of AD and PN. Clinical trials have demonstrated significant reductions in pruritus and cutaneous symptoms associated with its use. In clinical practice, acute eczema and edematous erythema frequently occur, occasionally necessitating the discontinuation of treatment. Despite these observations, no comprehensive review has examined nemolizumab-associated cutaneous adverse events. This review aimed to examine various cutaneous reactions associated with nemolizumab therapy, including psoriasiform eruptions, AD exacerbation, bullous pemphigoid, drug-induced eruptions, and fungal infections. Potential mechanisms underlying these reactions include T-cell activation due to drug sensitization, immune responses triggered by nemolizumab acting as a hapten, and a relative increase in IL-4 and IL-13 levels following IL-31 inhibition. However, the precise pathophysiological mechanism and risk factors remain unclear, and standardized clinical management guidelines are lacking. Further accumulation of clinical data and immunological research are essential for developing evidence-based strategies to manage these adverse events, ensuring treatment continuity and optimizing patient outcomes.

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BACKGROUND: Interleukin (IL)-31 affects the inflammatory response, is involved in epidermal barrier disruption in atopic dermatitis (AD) and plays a key role in pruritus. Nemolizumab, a humanized monoclonal antibody against IL-31 receptor A, reduced pruritus in patients with AD after a 16-week administration period. OBJECTIVES: To examine the long-term effectiveness and safety of nemolizumab in patients aged ≥ 13 years with AD and inadequately controlled moderate-to-severe pruritus. METHODS: In two long-term phase III studies, nemolizumab 60 mg every 4 weeks (Q4W) was administered subcutaneously, concomitantly with topical treatments. Study-JP01 patients received double-blind nemolizumab or placebo for 16 weeks, and then entered a 52-week extension period in which all patients received nemolizumab (nemolizumab/nemolizumab and placebo/nemolizumab groups). Study-JP02 patients received nemolizumab for 52 weeks. Both studies included an 8-week follow-up period. RESULTS: Study-JP01 nemolizumab/nemolizumab and placebo/nemolizumab, and Study-JP02 nemolizumab groups comprised 143, 72 and 88 patients, respectively. In the nemolizumab/nemolizumab group, there were clinically meaningful improvements from the start of treatment to week 68 in the pruritus visual analogue scale (66% decrease) and Eczema Area and Severity Index (78% decrease). Quality of life (QoL) indicators improved after the first nemolizumab dose; improvements were maintained during the follow-up period. The long-term safety profile was consistent with previous studies, with no unexpected late-onset adverse events. CONCLUSIONS: Nemolizumab 60 mg Q4W with concomitant topical treatments in patients with AD and inadequately controlled moderate-to-severe pruritus produced a continuous improvement in pruritus, signs of AD, and QoL for up to 68 weeks, with a favourable safety profile.

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