Nemolizumab (Nemluvio) was approved by the FDA in 2024 for treating patients 12 years and older with moderate-to-severe atopic dermatitis (AD) and adults with prurigo nodularis. This humanized monoclonal antibody works through the inhibition of cytokine interleukin-31 (IL-31) signaling, which underlies multiple atopic disorders.1 CD4+ Th2 cells are the main source of IL-31 and other cytokines. When IL-31 activates the IL-31 receptor A (IL31RA)/Oncostatin M receptor (OSMR) found on sensory nerves, inflammatory responses and pruritus are triggered.1 By inhibiting IL-31 downstream signaling, nemolizumab blocks associated inflammatory pathways and provides relief against pruritus, the cardinal symptom of AD.1 The advantages of nemolizumab over other medications for AD include rapid itch relief, lasting efficacy, a favorable safety and tolerability profile, and convenience for patients.

One of the most notable advantages of nemolizumab is its ability to provide rapid itch relief. In a phase III clinical study by Galderma Laboratories (ARCADIA 1),2 patients taking nemolizumab with a topical corticosteroid (TCS) and/or topical calcineurin inhibitor (TCI) experienced significant itch relief as early as 48 hours, compared to patients taking a placebo and TCS/TCI. This rapid itch relief was defined as ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS), a validated scale of worst itch intensity in adults with moderate-to-severe AD. At 14 days, there was still a significant difference in itch relief, with 22.7% of patients taking nemolizumab and TCS/TCI experiencing itch relief compared to just 10.6% of patients taking placebo and TCS/TCI.

Beyond short-term symptom control, nemolizumab demonstrates durable long-term efficacy. Efficacy was assessed using the Eczema Area and Severity Index (EASI), where a ≥75% reduction from baseline (EASI-75) indicates substantial improvement. In the ARCADIA 1 and 2 trials, 73% of patients with previous nemolizumab experience and 79% of first-time users achieved EASI-75 after 56 weeks of nemolizumab treatment.3 Additionally, ongoing and clinically meaningful improvements were measured by an Investigator’s Global Assessment (IGA) score of 0/1 (clear/almost clear). At 56 weeks, 47% of patients with previous nemolizumab experience and 49% of first-time users achieved IGA 0/1 with long-term treatment from baseline levels of 29% and 18%, respectively.3 Furthermore, long-term nemolizumab treatment also led to improvements in itch and sleep as measured by changes in the SCORing Atopic Dermatitis (SCORAD) score, which included itch and sleep visual analogue scale (VAS) components. Both groups, patients with previous nemolizumab experience and first-time users, had SCORAD Pruritus VAS scores that improved by 75% and SCORAD Sleep Loss VAS scores that improved by 70%, versus baseline scores, after 56 weeks of treatment.3 Thus, most patients still experience a strong effect of nemolizumab through clinically meaningful improvements in their AD, pruritus, and sleep after one year.

Complementing its efficacy, nemolizumab also maintains a favorable safety and tolerability profile. The most common adverse reaction was a headache, which was reported in 5% of the 1,135 patients assigned to nemolizumab versus 4% of the 584 patients assigned to placebo in the ARCADIA 1 study. The other reported reactions include arthralgia (1.1% with nemolizumab versus 0.2% with placebo), urticaria (1.1% with nemolizumab versus 0.3% with placebo), and myalgia (1% with nemolizumab versus 0.2% with placebo). Notably, nemolizumab is not associated with adverse reactions commonly associated with other biologics for AD, such as conjunctivitis. Furthermore, this biologic does not have boxed warnings or require laboratory monitoring.

Patient experience is further improved by its administration profile. Nemolizumab is delivered as a low-volume injection at 0.49 mL, smaller than other biologics used in AD treatment. Some patients have described the injection as being barely noticeable, potentially due to the low volume administered. Unlike many other biologics for AD, nemolizumab does not result in injection site reactions. The limited adverse reactions and ease of administration contribute to its strong safety and tolerability advantages.

Convenience is another key factor contributing to nemolizumab’s appeal. For patients aged 12 years and older with AD, the FDA-approved regimen is 60 mg subcutaneously (two 30-mg injections) at baseline, then 30 mg every four weeks for four months. After four months, the maintenance dosing becomes one injection every eight weeks for patients who achieve clear or almost clear skin. Thus, on maintenance, a patient with AD may have as few as six shots per year.

Adding to this convenience is its flexible storage capability. Nemolizumab can be stored at room temperature for 90 days. This feature makes it especially suitable for patients without consistent access to refrigeration, such as frequent travelers or individuals with marginalized housing. With its favorable dosing interval and convenient storage mechanism, nemolizumab is well-suited to support adherence and improve access for many patients with AD.

Nemolizumab is just one advanced systemic therapy for moderate-to-severe AD and differs from other therapies, such as dupilumab and oral JAK inhibitors, in terms of mechanism, efficacy, and safety. While nemolizumab’s mechanism of action is through targeting the IL-31RA, dupilumab, another subcutaneous monoclonal antibody, blocks IL-4 and IL-13, which are central drivers of AD.4 Dupilumab is approved for patients as young as 6 months, and the American Academy of Allergy, Asthma, and Immunology recommend dupilumab as a first-line biologic for moderate-to-severe AD.5 In terms of efficacy, one real-world study showed that 100% of 17 patients after 52 weeks of dupilumab treatment achieved EASI-75.6,7 Dupilumab’s common adverse events include injection site reactions and conjunctivitis.8 Other therapy options for AD, oral JAK1 inhibitors like abrocitinib and upadacitinib, block JAK-STAT signaling, disrupting Th2 differentiation and cytokine activity involved in inflammatory skin diseases like AD.9 Abrocitinib has been shown to have a faster effect than dupilumab in alleviating pruritus, and the expected EASI-75 response rate estimates at week 12 are 62.9% for abrocitinib 200 mg.10 However, JAK inhibitors carry increased risks of infection, requiring screening for latent tuberculosis, and have potential for laboratory-related adverse events.10 Together, these therapies offer diverse options for tailoring treatment of moderate-to-severe AD based on individual patient needs, balancing efficacy, safety, and speed of symptom relief.

In summary, nemolizumab stands out as a highly effective and patient-friendly biologic for AD. It provides rapid pruritus relief for patients with moderate-to-severe AD in as early as 48 hours. Nemolizumab has long-lasting efficacy for patients who use it for at least a year. The safety profile of nemolizumab is favorable, characterized by minimal adverse events and a low-volume injection formulation. Unlike many other biologics for AD, nemolizumab is unique, with a dosing interval requiring as few as six shots per year on maintenance, and it can be conveniently stored at room temperature for up to 90 days. These attributes support nemolizumab as an important therapeutic option for managing pruritus and skin inflammation in patients with moderate-to-severe AD.