{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:04:03Z","timestamp":1784379843978,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ligelizumab is a highly potent, humanized IgG1 anti\u2010IgE monoclonal antibody that was developed to treat chronic spontaneous urticaria (CSU). The immunogenicity of ligelizumab and its clinical impact were investigated in CSU patients following subcutaneous administration of 72 or 120\u2009mg ligelizumab once every 4\u2009weeks based on pooled data from two pivotal phase 3 clinical trials (PEARL\u20101 and PEARL\u20102). Across the 72\u2009mg ligelizumab, 120\u2009mg ligelizumab and placebo transitioned 120\u2009mg ligelizumab arms, treatment\u2010emergent anti\u2010drug antibodies (TE\u2010ADAs) were observed in 20.0%\u201322.6% of patients, out of whom 78.0%\u201381.7% developed neutralizing antibodies. The majority (&gt;\u200999%) of patients with TE\u2010ADAs had treatment\u2010induced ADAs and 74.0%\u201390.0% developed a persistent ADA response. ADA titers became detectable in Week 12 after start of ligelizumab treatment and reached plateau around Week 20, with the median ADA onset at 143\u2013147\u2009days. In the 72 and 120\u2009mg ligelizumab arms, the geometric mean steady\u2010state trough concentration of ligelizumab was 52% and 41% lower, and the pharmacodynamic marker total IgE (% change from baseline) was 71% and 66% lower in ADA\u2010positive than in ADA\u2010negative patients, respectively. However, primary efficacy endpoint (change from baseline in Urticaria Activity Score 7) and key safety endpoints (incidence of treatment\u2010emergent hypersensitivity and injection\u2010site reactions) did not show clinically meaningful difference between ADA\u2010positive and ADA\u2010negative patients. This comprehensive analysis is the first report characterizing the immunogenicity profile of ligelizumab. The results indicate that ADAs reduced ligelizumab pharmacokinetic exposure and target engagement but had no clinically relevant impact on efficacy or safety in patients with CSU.<\/jats:p>","DOI":"10.1111\/cts.70661","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T03:14:11Z","timestamp":1783998851000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ligelizumab Immunogenicity and Impact on Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety in Patients With Chronic Spontaneous Urticaria"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9569-0574","authenticated-orcid":false,"given":"Yan","family":"Ji","sequence":"first","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5626-7204","authenticated-orcid":false,"given":"Claudio","family":"Calonder","sequence":"additional","affiliation":[{"name":"Novartis BioMedical Research  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina","family":"Kirsil\u00e4e","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alis","family":"Burciu","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Laurent","sequence":"additional","affiliation":[{"name":"Novartis BioMedical Research  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5781-170X","authenticated-orcid":false,"given":"Eva","family":"Hua","sequence":"additional","affiliation":[{"name":"China Novartis Biomedical Research Co. 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