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Compared to treatment with a placebo, patients with moderate to severe prurigo nodularis treated with nemolizumab demonstrated modulation of epithelial differentiation, inflammatory signaling, and neural development.

Prurigo nodularis is a dermatological condition that involves hyperkeratotic skin nodules and intense pruritus. Nemolizumab is a monoclonal interleukin 31 receptor α antibody that represents a novel therapeutic strategy in moderate to severe prurigo nodularis. Deng et al. conducted a multicenter cohort study to identify modulation in the plasma protein biomarkers in response to treatment with nemolizumab in prurigo nodularis patients. The study findings are published in JAMA Dermatology.

Study Characteristics

The multicenter cohort included 38 moderate-to-severe prurigo nodularis patients, 16 male and 22 female, from the United States, Austria, France, Poland, and Germany. The mean age of the participants was 55.8 ± 15.8 years. The patients were equally divided into placebo and nemolizumab groups, which received the assigned medication at 0-, 4-, and 12-week intervals.

Clinical Efficacy of Nemolizumab in Prurigo Nodularis

In the nemolizumab group, approximately 89% of the patients demonstrated a minimum of four points of decline in the Peak Pruritus Numerical Rating Scale (PP-NRS) at the fourth week compared to no improvement in the PP-NRS score for placebo group patients. This difference was statistically significant. The Investigator’s Global Assessment (IGA) score, measured at week 18, was improved in 53% of the nemolizumab group patients, compared to no IGA success in the placebo group patients.

Nemolizumab and Plasma Protein Biomarkers

Nemolizumab treatment was associated with the differential expression of 193 proteins. The proteins included melanoma cell adhesion molecule, filaggrin 2, and keratin 9 for tissue remodeling and structure; oncostatin M, CD59, and caspase 4 for inflammatory activation; transforming growth factor ß (TGF-ß), M-Ras, and H-Ras for cellular differentiation and growth. Nemolizumab treatment was associated with the downregulation of pruritus, neural dysregulation, and inflammatory signaling as well as growth factor-mediated epithelial–mesenchymal transition.

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Study Limitations

The study was performed on a subset of patients from a phase 2 clinical trial, and the patients were not randomized into placebo and nemolizumab groups, which may lead to potential bias in the findings reported. Future studies may include randomized patient cohorts to determine the validity of this study’s findings.


Deng, J., Liao, V., Parthasarathy, V., Cornman, H., Kambala, A., Kwatra, M. M., Ständer, S., Piketty, C., Chaskar, P., Krishnaswamy, J. K., Julia, V., & Kwatra, S. G. (2023). Modulation of neuroimmune and epithelial dysregulation in patients with moderate to severe prurigo nodularis treated with nemolizumab. JAMA Dermatology. https://doi.org/10.1001/jamadermatol.2023.2609