Loading ...

A recently published case series illustrates how a treatment approved last year for two conditions associated with pruritus could be useful in alleviating itch in patients with a broad variety of other conditions, many of which have a few or no treatment options.

In the case series of 70 patients, treatment with nemolizumab — an interleukin (IL)-31 receptor alpha-antagonist approved by the FDA for the treatment of prurigo nodularis (PN) and atopic dermatitis (AD) in 2024 — dramatically reduced itching in a range of additional conditions that cause pruritus.

“Itching causes tremendous suffering,” Jenny Murase, MD, associate clinical professor of dermatology, University of California San Francisco, and one of the authors of the case series, told Medscape Medical News. “To be unable to sleep and unable to concentrate during the day because the itching is so intense and distracting, to feel like you don’t want to live in your own skin — these are incredibly debilitating.”

Pruritus, defined as “an unpleasant sensation that provokes the desire to scratch,” can “range in intensity from a mild annoyance to an intractable, disabling condition.”

Murase, director of Medical Consultative Dermatology and Patch Testing, Palo Alto Medical Foundation, Mountain View, California, said some patients have likened pruritus, which is often accompanied by sensations similar to electric shocks, to being “tortured.” Many of her patients have tried up to 30 medications, including topical, oral, and injectable agents, receiving minimal if any relief.

The multicenter case series examining medical records of 70 patients found nemolizumab dramatically reduced itching in patients with a range of additional conditions that cause pruritus, as measured using the Peak Pruritus Numerical Rating Scale (NRS). The patients described in the report, published in March in the Journal of the American Academy of Dermatology, did not respond to 12 therapies on average.

“The findings of our case review matched my clinical experience using this agent,” Murase said. “We were excited to uncover the wide range of conditions that responded to it.”

In other recently published case reports, authors have described patients with cholestatic pruritus and pruritus of unknown origin who experienced relief from severe pruritus with nemolizumab. In late June, Galderma, the manufacturer of nemolizumab, announced that two clinical trials have been launched to investigate the role of nemolizumab in treating chronic pruritus of unknown origin and systemic sclerosis.

Targeting the ‘Itch Cytokine’

Murase explained that IL-31 is sometimes called the “itch cytokine.” Because nemolizumab is an IL-31 inhibitor, it works directly on sensory neurons regardless of the underlying cause of the pruritus. In her clinical experience, “the relief from the itching is extremely fast for the patient after, in some cases, decades of daily itching.”

For example, one of her patients with severe pruritus, who was in the case series, did not respond to 30 medications, including JAK inhibitors, IL-4 and IL-13 inhibitors, and neuropathic agents such as pregabalin and gabapentin; was unable to work or sleep; and was forced to quit his job. “After a single injection of nemolizumab, his symptoms disappeared within 10 days,” Murase said. After 12 days, some mild itching reappeared, “but his improvements have been largely sustained, and he feels he has his life back for over 8 months now.”

Murase and her colleagues were so struck by the potential utility of nemolizumab beyond the two conditions for which it is approved by the FDA that they conducted the case series involving retrospective data collection from medical records of patients who had been treated with nemolizumab for skin diseases associated with pruritus (60 patients) or for burning (10 patients).

Conditions affecting these patients included AD, nummular dermatitis, hand dermatitis, dermatographia urticaria, cutaneous mastocytosis, neuropathic itch, subacute prurigo, immunologic eruptions of aging, lymphoma/leukemia, scrotal pruritus, vulvar/anal pruritus, acquired cutaneous brachioradial pruritus, notalgia paresthetica, scabies, post-scabetic Id hypersensitivity, lichen amyloidosis, pernio, and granulomatous dermatitis. Patients experiencing burning had neuropathic skin pain, burning mouth syndrome, neurogenic rosacea, and erythromelalgia.

Patients received an initial dose of 60 mg, followed by monthly treatments of 30 or 60 mg, and were followed for an average of 73 days.

All 70 patients were considered responders, as defined by a reduction in the NRS score of ≥ 2 and/or a 50% reduction in baseline symptoms, except for one out of two cases of notalgia paresthetica (no response) and acquired cutaneous brachioradial pruritus. Murase noted that the latter patient continued treatment regardless and responded at the 5-month mark after the publication of the case series. Almost all patients (96%) opted to continue taking the medication.

“Many patients started out with an NRS score of 9 or 10, and then their score went to 0 within 2 days. It was truly remarkable,” Murase said in the interview.

Investigate Medical Causes Before Prescribing

As she and her coauthors noted, Murase expressed a significant concern particularly relevant to patients with no visible cutaneous manifestations such as rash, which could account for their pruritus. In the case series, three patients had leukemia/lymphoma, 20% had renal insufficiency, and 36% had either diabetes or prediabetes. “All these conditions can predispose patients to have neuropathy and pruritus without a visible rash. Immediately prescribing nemolizumab without thoroughly assessing other potential causes of the itch — especially in lymphoma and leukemia, which can present only with pruritus and no other symptoms — might lead to missed diagnoses of these conditions,” she cautioned.

She recounted the story of a male patient in his thirties with dermatographia and no response to an array of previous medications. Murase ordered a hepatitis titer test and a tuberculosis screen, as well as a chest x-ray in preparation to place him on a JAK inhibitor before nemolizumab was available for her to prescribe. She ordered a chest x-ray for an indeterminate QuantiFERON result and diagnosed Hodgkin lymphoma.

“He is alive today because of this,” she commented. “If I had given him nemolizumab immediately, I would have gotten rid of the only sign that he had lymphoma. The itch reduction is so powerful with the medication that I really want providers to do thorough assessment for malignancy or metabolic conditions before they place their patients on this medication.”

Financial Challenges in Prescribing Nemolizumab

Murase noted that because nemolizumab is approved only for AD or PN, prescribing it for any other indication is off label, and patients often struggle to get their insurance companies — especially Medicare — to cover the treatment. “Patients need to have a history of AD, such as a history of rashes in childhood and adulthood, itching, a relapsing and remitting nature, history of hay fever, history of asthma, history of family members with allergies, asthma, and hay fever, to suggest that they could have AD. Or they need to have excoriated lesions for a PN diagnosis.” She noted that these are clinical diagnoses.

Murase said that patients in the area where she practices usually have the means to pay out of pocket, and many patients are willing to spend what it takes to obtain the drug because it offers such profound relief. “I’m hoping that Medicare coverage — and coverage offered by other insurance companies — will improve over time,” she said.

Adverse Effects

Most patients in the case series experienced no side effects; however, one patient developed facial swelling and erythroderma thought to be caused by discontinuation of abrocitinib. In general, Murase said, nemolizumab has a fairly benign side-effect profile — something she has observed in her own clinical practice.

The prescribing information for nemolizumab (Nemluvio) lists the most common adverse reactions (affecting 1% or more of patients) as headache, AD, eczema, and nummular eczema with PN and headache (including migraine), arthralgia, urticaria, and myalgia with AD. A 2025 review of cutaneous adverse events following administration of nemolizumab found an increased incidence of psoriasiform eruptions, AD exacerbations, bullous pemphigoid, nonspecific drug-induced eruptions, fungal infections, urticaria, acne, and contact dermatitis in patients receiving nemolizumab and overall cutaneous adverse events in about 30%-50% of patients. A review and meta-analysis of three studies of nemolizumab for PN encompassing almost 500 patients found no difference between nemolizumab and placebo in the rates of adverse events or serious adverse events.

Transforming the Landscape

Commenting for Medscape Medical News, Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, DC, said that “pruritus is not just a symptom; it’s a disease in and of itself and one that deserves targeted therapy.”

The case series by Murase and colleagues, he said, “reinforces what we’ve seen clinically, which is that nemolizumab can provide rapid and profound relief for patients with a wide range of underlying conditions, including those with inflammatory and more difficult-to-manage idiopathic itch.”

Nemolizumab has “transformed the landscape” of PN, an on-label use, Friedman said. He has also prescribed it for itch associated with systemic lupus erythematosus, pruritus associated with various cancer treatments, idiopathic pruritus in older adult patients, and even delusions of parasitosis, “where traditional antipruritics fall short.”

Friedman, also director of translational research and director of supportive oncodermatology at George Washington University, noted that his clinical experience accords with the findings of the case series that nemolizumab “tends to disappoint” in centrally mediated conditions such as notalgia paresthetica and brachioradial pruritus. And he echoed Murase’s caveat that “diagnostic rigor is critical.”

He added that itch is “very personal,” so clinicians should “tailor therapy, set expectations, and reassess frequently.”

Also commenting for Medscape Medical News, Lauren Ploch, MD, MEd, of Georgia Dermatology & Skin Cancer Center in Augusta and Aiken, South Carolina, agreed that the workup of patients without primary skin lesions should include ruling out medical causes such as renal disease and malignancies, and that patients should be monitored — although some of the newer medications “do not require strict lab monitoring.”

Murase added that nemolizumab can be useful in every medical specialty that treats patients with pruritus. “For example, vulvar pruritus drives patients crazy. I heard about one patient who was literally sitting on ice throughout the day because her symptoms of itching and burning were so life-altering. Within a few days of treatment [with nemolizumab], her symptoms had abated.”

In addition, she said, it is also an option for urologists treating scrotal itch, “which can be horrific even though there is very little to see on the skin. And one of the most debilitating symptoms of chronic kidney disease is pruritus, which has been shown to sap quality of life in these patients more than other symptoms. Now, nephrologists have something to offer these patients.”

Murase and her colleagues are in the process of publishing a post hoc analysis of the rapidity of itch relief with nemolizumab in patients with pruritus.

The study received no funding. Murase reported being on the speakers board for Galderma, UCB, Leo Pharma, Eli Lilly, AbbVie, and Sanofi-Regeneron; serving on advisory boards for UCB, Galderma, Arcutis, Eli Lilly, Leo Pharma, Sanofi-Regeneron, and Bristol Myers Squibb; and providing dermatologic consulting services for UCB, Apogee Therapeutics, Galderma, AbbVie, Attovia, Sanofi-Regeneron, and UpToDate. Friedman reported being a speaker, investigator, and consultant for Galderma. Ploch reported having no relevant financial relationships.

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape Medical News and WebMD, and is the author of several consumer-oriented health books, as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).