The Show Must Go On

An Update on Clinical Experiences and Clinical Studies on Novel Pharmaceutical Developments for the Treatment of Atopic Dermatitis

Tatjana Honstein; Thomas Werfel

Disclosures

Curr Opin Allergy Clin Immunol. 2020;20(4):386-394. 

In This Article

Targeting IL-31 RA for the Treatment of Atopic Dermatitis With Nemolizumab

Three therapeutical targets for atopic dermatitis discussed in this overview are directly involved in inducing itch in addition to cytokine type 2-skewed inflammatory responses: IL-31, TSLP, and histamine. Effects of IL-31 are discussed in detail by Topal et al.[29] in this issue of Current Opinion in Allergy & Clinical Immunology. IL-31 acts via a complex of IL31RA and the onkostatin M receptor ß, which is expressed in immune and epithelial cells and on sensory nerves. Interestingly, this antibody was recently successfully applied also in patients suffering from very high pruritus in prurigo nodularis in a placebo-controlled phase II study.[30]

Following a well performing phase I study, nemolizumab was tested in patients with moderate-to-severe pruritic atopic dermatitis in a phase II study. The initial evaluation of a study of 12 weeks on 216 patients showed major effects on the reduction of pruritus.[31] Patients from this study entered an extension regimen and continued treatment for another 52 weeks.[32] The study endpoint showed a solid improvement in visual analogue scale (VAS) value for pruritus between 73 and 90% from baseline. During extension, the change in EASI score was also markedly reduced between 69 and 79%. The overall Dermatology Quality of Life Index (DLQI) score decreased progressively in patients receiving nemolizumab. The most common treatment-related adverse effects were exacerbation of atopic dermatitis, upper respiratory tract infections, nasopharyngitis, peripheral edema, elevated blood creatine phosphokinase levels, and injection site responses, usually of mild-to-moderate intensity. An additional dose-adjustment study was performed in 226 adult participants.[33] Patients received placebo or 10, 30, 90 mg of nemolizumab applied subcutaneously every 4 weeks for 24 weeks. Efficacy was determined with EASI, IGA, and NRS pruritus scores compared with the placebo group and it turned out that the 30 mg dose led to best efficacy showing significant reduction not only of pruritus but also of clinical signs (measured by EASI) already after 16 weeks.

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