Nemolizumab for chronic pruritus beyond atopic dermatitis and prurigo nodularis: a systematic review and synthesis of emerging evidence

Nemolizumab, an anti-IL-31 receptor A antibody, is licensed for atopic dermatitis and prurigo nodularis; its role in other chronic pruritus (CP) syndromes is uncertain.
To synthesize efficacy, safety and strength of evidence for nemolizumab in CP beyond these indications. Methods: We conducted a PROSPERO-registered systematic review (CRD420251207054) of databases and trial registries to November 2025 for nemolizumab studies in CP outside AD/PN. Eligible reports were extracted and patients grouped as systemic, neurologic/neurogenic, dermatologic (non-AD) or primary CP/CP of unknown origin.
Seventeen reports (one randomized trial, two cohorts, 14 case series/reports) describing 114 patients were included. In chronic kidney disease-associated pruritus, a phase II hemodialysis trial showed modest, statistically uncertain benefit versus placebo, contrasting with rapid, near-complete relief in dialysis and cholestatic case reports. Uncontrolled data in neuropathic itch/pain syndromes, non-AD inflammatory and papular dermatoses (notably amyloidosis and perforating disorders) and long-standing primary CP/CPUO described complete itch clearance. Across indications, nemolizumab was well tolerated, but certainty was low for CKD-aP and very low for other groups.
Nemolizumab shows plausible antipruritic activity across CP phenotypes, yet the evidence base remains fragile; these signals justify cautious experimental use and prioritize etiology-specific IL-31 receptor blockade trials beyond AD/PN.