Nemolizumab Therapy for Moderate-to-Severe Prurigo Nodularis
1. Nemolizumab may reduce inflammatory, neural, and epithelial signalling in patients with prurigo nodularis by inhibiting IL-31.
2. Nemolizumab may be an effective monoclonal antibody treatment for moderate-to-severe prurigo nodularis.
Evidence Rating Level: 2 (Good)
Study Rundown: Prurigo nodularis (PN) is a chronic inflammatory dermatosis characterized by hyperkeratotic nodules. PN often adversely affects the quality of life due to pruritus, pain, and loss of sleep. PN is linked to increased inflammatory cytokines, including interleukin 4 (IL-4), IL-13, IL-31, IL-17, IL-22, and IL-31. Neomlizumab is a monoclonal antibody that targets IL-13, promoting pruritus and skin lesion improvement; however, the biological mechanisms are unknown. This retrospective cohort study investigated the plasma and epidermal protein expression changes in patients with PN treated with nemolizumab, finding that nemolizumab modulates inflammatory signalling, neural development, and epithelial differentiation. Limitations of this study include a small sample size and a lack of disease heterogeneity due to the exclusion criteria.
Click to read the study in JAMA Dermatology
Click to read an accompanying editorial in JAMA Dermatology
Relevant Reading: IL-31 Inhibition as a therapeutic approach for managing chronic pruritic dermatoses
In-Depth [retrospective cohort]: Data included in this study was obtained from patients who had clinical improvement, in moderate to severe PN, in a previous placebo-controlled, double-blind phase 2 randomized clinical trial. The included patients were recruited from centers in Austria, France, Germany, Poland, and the United States of America. For patients in the clinical trial, inclusion criteria consisted of adults with moderate to severe PN and severe pruritus for at least six months (i.e., an average of at least 7 over the previous week on a scale from 0 [no itch] to 10 [worst itch imaginable]). Moderate-to-severe PN was defined as upper extremity nodules (with or without truncal or lower extremity lesions), at least 20 nodules on the body, and a lesion distribution on both sides of the body. Exclusion criteria included pruritus from another condition, unilateral lesions, or neuropathic or psychogenic pruritic signs. Plasma samples from 38 patients (22 women and 16 men; mean [SD] age, 55.8 [15.8] years) who had a nemolizumab response or placebo nonresponse were obtained at baseline, week 4, and week 12. A nemolizumab response was defined as a ≥ 4-point decrease in the Peak Pruritus Numerical Rating Scale (PP-NRS) from baseline to week 12. In contrast, a placebo nonresponse was defined as not experiencing a ≥ 4-point reduction in the PP-NRS from baseline to week 12 while on placebo therapy. Then, protein mass spectrometry, differential expression, and enrichment analysis were conducted for the samples. In total, there were 194 differentially expressed plasma proteins. In the nemolizumab group, there was a downregulation of inflammation, neural processes (i.e., synaptogenesis signalling and neuritogenesis), tissue remodelling and fibrosis, and epidermal differentiation (i.e., epithelial-mesenchymal transition). For inflammation, specifically, IL-6 acute-phase response, signal transducer and activator of transcription 3, and interferon-gamma were reduced. For tissue remodelling and fibrosis, the specific factors reduced were transforming growth factor beta 2 and endothelin-1. Overall, nemolizumab may be a promising approach for PN clinical management.
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