{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:43:41Z","timestamp":1791413021675,"version":"4.3.3"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prurigo nodularis (PN), a chronic inflammatory skin disease with significant disease burden, lacks effective therapies. Dupilumab (IL-4R\u03b1 inhibitor) and nemolizumab (IL-31 receptor antagonist) show efficacy in trials but have heterogeneous safety data without direct comparisons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To indirectly compare safety profiles of dupilumab and nemolizumab in PN, addressing trial design heterogeneity (efficacy endpoints, treatment durations, safety reporting).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Following PRISMA guidelines, five RCTs (dupilumab: 2 trials; nemolizumab: 3 trials) were analyzed. Safety outcomes [adverse events (AEs), serious AEs (SAEs), treatment discontinuation, mechanism-specific events] were standardized via time-proportional hazard models. Risk ratios (RR) and absolute risk differences (ARD) were calculated using Cochrane tools and indirect comparison frameworks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>In standardized indirect comparisons, dupilumab and nemolizumab showed broadly similar safety profiles for overall adverse events (indirect RR\u202f=\u202f1.11, 95% CI:0.85\u20131.47; moderate certainty), serious adverse events and treatment discontinuation. Exploratory analyses of mechanism-specific events revealed non-significant directional differences requiring cautious interpretation: dupilumab showed a numerically higher incidence of conjunctivitis (RR\u202f=\u202f2.01, 95% CI:0.29\u201313.77) with confidence intervals spanning two orders of magnitude, while nemolizumab showed a similar pattern for edema (RR\u202f=\u202f1.64, 95% CI:0.52\u20135.18). These signals, derived from sparse event data (n\u202f\u2264\u202f15 cases) and overlapping confidence intervals across all comparisons, should be regarded as hypothesis-generating rather than confirmatory evidence. Limitations inherent to indirect methodology \u2013 including trial design heterogeneity (endpoint definitions: IGA PN-S vs. PP-NRS; duration:12\u201324\u202fweeks) and absence of severity-stratified reporting \u2013 preclude definitive safety conclusions. All comparisons must be interpreted within the constraint of unmeasured confounding factors potentially influencing indirect estimates.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1626395","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:33:13Z","timestamp":1762929193000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative safety profiles of dupilumab and nemolizumab in prurigo nodularis: an indirect META-analysis to inform clinical decision-making"],"prefix":"10.3389","volume":"12","author":[{"given":"Wenzhe","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyue","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1001\/jamadermatol.2021.5307","article-title":"Prurigo nodularis","volume":"158","author":"Kwatra","year":"2022","journal-title":"JAMA Dermatol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.jid.2019.07.697","article-title":"Real-world 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