Targeting the neuroimmune axis in prurigo nodularis: a critical appraisal of the nemolizumab trials

<b>Background:</b> Prurigo nodularis (PN) is a chronic, debilitating neuro-immunological skin disease characterized by intense pruritus and hyperkeratotic nodules. Nemolizumab, a novel IL-31 receptor alpha antagonist targeting the neural itch pathway, was investigated in PN.<b>Areas covered:</b> Two randomized phase 3 studies, the Olympia 1 and Olympia 2 trials, provided favorable efficacy and safety data for nemolizumab versus placebo in moderate-to-severe PN. After 16 weeks, a ≥4-point reduction in PP-NRS was achieved in 58.4% (Olympia 1) and 56.3% (Olympia 2) of nemolizumab patients compared to 16.7% and 20.9% in placebo groups, respectively (<i>p</i><0.001). Safety data showed no drug-related serious adverse events or organ toxicity.<b>Expert opinion:</b> These trials were the first to clinically demonstrate IL-31 inhibition in PN. Nemolizumab represents a paradigm shift in PN therapy, acting as a potent "neuro-modulator" with rapid itch relief, often observed by Week 4.<b>Conclusions:</b> Future management may rely on disease endotypes to select between neural (IL-31) and immune (IL-4/13) blockade.