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Article

IL-31 pathway may lead to new treatments for pruritus

Author(s):

In early research, subcutaneous nemolizumab significantly reduced pruritus in moderate-to-severe atopic dermatitis adult patients.

Nemolizumab (CIM331, Chugai Pharmaceutical), studied at various doses in a phase 2 trial, improved pruritus in adults with moderate-to-severe atopic dermatitis, suggesting the humanized antibody effectively targets interleukin-31 (IL-31) receptor-A in these patients, according to a study published earlier this year in the New England Journal of Medicine.

“The predominant early immunologic response in atopic dermatitis includes type 2 helper T (Th2) cells, innate lymphoid cells and keratinocytes that produce the type 2 cytokines, such as thymic stromal lymphopoietin (TSLP, a major promoter of atopy) and interleukins 4, 13 and 31,” writes Lynda C. Schneider, M.D., director of the allergy program and professor of pediatrics at Harvard Medical School in an editorial accompanying the NEJM-published study.

IL-31 has important roles in atopic dermatitis and alopecia, according to a review of studies, published March 2017 in the Journal of Dermatological Treatment, looking at IL-31’s role in atopic dermatitis.

The review’s authors, from Wake Forest School of Medicine, Winston-Salem, N.C., reported that IL-31 overexpression results in clinical and histological features consistent with atopic dermatitis, as well as induces reversible alopecia. They concluded that inhibiting this pathway could offer an alternative to the use of antihistamines for treatment of pruritus in atopic dermatitis patients.3

The phase 2 study in NEJM was a 12-week randomized, double-blind, placebo-controlled trial looking at 264 adults with moderate-to-severe atopic dermatitis, who had been inadequately controlled by topical treatments. Subjects were randomized to one of four dosage groups, receiving nemolizumab at 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight or placebo every four weeks, or an exploratory dose of 2.0 mg of nemolizumab per kilogram every eight weeks, according to the study’s abstract.

Of the 264 that started the study, 82 percent, or 216 patients completed it.

They found nemolizumab significantly improved pruritus at all the doses studied. At 12 weeks, the pruritus visual analogue scale (VAS), where patients indicate itch severity from zero, which means no itch, to 10, the worst imaginable itch, was -43.7 percent for nemolizumab 0.1 mg/kg; -59.8 percent at the 0.5 mg/kg dosage; and -63.1 percent for nemolizumab at 2.0 mg/kg compared to -20.9 percent in the placebo group.

The researchers looked secondarily at the change in the Eczema Area and Severity Index (EASI) score, which measures dermatitis severity with a score of zero to 72. By week 12, patients in the 0.1 mg/kg nemolizumab group had a change in EASI of -23.0 percent; in the 0.5 mg/kg the change was -42.3 percent; and in the 2.0 mg/kg it was -40.9 percent. That was compared to -26.6 percent in the placebo group.

Reported changes in body surface area impacted by atopic dermatitis were -7.5 percent in the 0.1-mg/kg group; -20.0 percent in the 0.5 mg/kg, -19.4 percent in the 2.0 mg/kg arm, versus -15.7 percent with placebo.

Among the common adverse events: worsening atopic dermatitis, nasopharyngitis, upper respiratory tract infections, peripheral edema and increased creatine phosphokinase, according to a company press release. But the study was too small and short to adequately report on adverse events, according to the study authors.

“Nemolizumab is the first drug specifically targeting pruritus. Its use is very convenient to patients with one subcutaneous injection per month,” NEJM study author and Professor Thomas Ruzicka, M.D., of Ludwig-Maximilian University Munich, said in the Chugai release. “Since IL-31 is involved in a variety of other pruritic skin diseases, the innovative drug has a large potential in dermatology.”

 

DISCLOSURES

This study was funded by by Chugai Pharmaceutical.

 

REFERENCES

1. Thomas Ruzicka, M.D., Jon M. Hanifin, M.D., Masutaka Furue, M.D., Ph.D., et al. “Anti–Interleukin-31 Receptor A Antibody for Atopic Dermatitis,” New England Journal of Medicine. March 2, 2017.  DOI: 10.1056/NEJMoa1606490 (http://www.nejm.org/doi/full/10.1056/NEJMoa1606490)

2. Lynda C. Schneider, M.D. “Ditching the Itch with Anti–Type 2 Cytokine Therapies for Atopic Dermatitis,” New England Journal of Medicine. March 2, 2017. DOI: 10.1056/NEJMe1616072 (http://www.nejm.org/doi/full/10.1056/NEJMe1616072)

3. Saleem MD, Oussedik E, D'Amber V, Feldman SR. “Interleukin-31 pathway and its role in atopic dermatitis: a systematic review.” J Dermatolog Treat. 2017 March 2, 2017. DOI: 10.1080/09546634.2017.1290205. (https://www.ncbi.nlm.nih.gov/pubmed/28145790)

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