Nemolizumab Improved Clinical Severity of Prurigo Nodularis

Researchers analyzed the association of interleukin 31 receptor α (IL-31RA) inhibition with plasma protein expression in nemolizumab (Galderma) in managing prurigo nodularis (PN) and found that nemolizumab is associated with modulation of neural, inflammatory, and epithelial signaling.¹

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Following a randomized, double-blind phase 2 study of patients with moderate to severe PN, Deng et al conducted a cohort study of 38 patients and measured changes in plasma and epidermal protein expression. Plasma samples of the 19 patients in the treatment group and the 19 patients in the placebo group were taken at baseline and at weeks 4 and 12.

Peak Pruritus Numerical Rating Scale (PP-NRS) scores and Investigator’s global assessment (IGA) scores were similar between the group treated with nemolizumab and the group treated with placebo at baseline. Within the treatment group, 17 of the 19 (89%) patients experienced at least a 4-point decrease (improvement) in PP-NRS score compared to 0 of the 19 in the placebo group.

Researchers found 193 proteins were differentially expressed after nemolizumab treatment compared to placebo. Inflammatory signaling pathways of vascular endothelial growth factor (VEGF), Interleukin-6 (IL-6), and acute phase response were downregulated, and regulation of the epithelial mesenchymal transition by growth factor was increased. The synaptogenesis signaling pathway was downregulated in the treatment group, “emphasizing the importance of IL-31 as a neuroinflammatory cytokine in PN.”

The terms myeloid cell movement, cell movement of leukocytes, and leukocyte migration decreased in the treatment group, indicating an effect of nemolizumab on cellular infiltration. There was also a decrease in cell death of neuroglia, and downregulation of terms related to epithelial differentiation and fibrosis.

“[T]his proteomics study demonstrates that systemically, nemolizumab response was associated with improved clinical severity of PN through mediation of acute-phase responses and tissue remodeling, neural development, and epidermal differentiation, compared with placebo nonresponse,” Deng et al concluded.

A limitation of the study was that it was conducted on a subset of 19 patients in a nemolizumab response group and 19 patients in a placebo nonresponse group from the original phase 2 study for PN.

Reference

1. Deng J, Liao V, Parthasarathy V, et al. Modulation of neuroimmune and epithelial dysregulation in patients with Moderate to severe prurigo nodularis treated with nemolizumab. JAMA Dermatol. Published online August 09, 2023. doi:10.1001/jamadermatol.2023.2609