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Serum biomarkers could aid biologic selection and dose modifications to improve patient outcomes while encouraging cost\u2010effective care.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To explore the exposure\u2013response relationship for guselkumab (GUS), to define a GUS concentration target for optimal response and to evaluate the potential of serum protein levels as predictive biomarker candidates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a prospective, multicentric, cohort study in psoriasis patients treated with GUS. Serum GUS trough concentrations (TCs) collected at multiple timepoints were measured using an in\u2010house immunoassay. Next, proximity extension assay technology (Target 96 Inflammation Panel Olink\u00ae) was used to measure serum protein levels in a subcohort including 38 GUS patients (week 0 and week 4), six psoriasis patients naive for systemic treatment and four healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventy\u2010five patients participated and 400 samples were collected. Guselkumab TCs and clinical response were correlated at week 4, week 12 and in steady\u2010state (\u226520\u2009weeks). Optimal responders (Psoriasis Area and Severity Index [PASI]\u2009\u2264\u20092) had significantly higher TCs than suboptimal responders from week 4 onwards in treatment. An optimal steady\u2010state TC of 1.6\u2009\u03bcg\/mL was defined. Although TC and absolute PASI were lower and worse, respectively, in patients weighing \u226590\u2009kg, clinical outcomes referred to desirable to excellent PASI ranges. Therefore, we do not recommend systematically higher GUS doses in obese patients. We could not reveal early differentially expressed proteins to distinguish future optimal from suboptimal responders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrated an exposure\u2013response relationship for GUS and an optimal steady\u2010state TC of 1.6\u2009\u03bcg\/mL in real\u2010world psoriasis patients. Hereby, we deliver more evidence that therapeutic drug monitoring poses a promising strategy in optimizing GUS treatment. No biomarker candidates were identified through serum proteomics. We propose protein screening should be repeated in larger cohorts to continue the quest for predictive biomarkers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.20074","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T13:44:57Z","timestamp":1715175897000},"page":"1555-1565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>Exposure\u2013response<\/scp> relationship of guselkumab and the potential of serum proteomics in identifying predictive biomarker candidates in psoriasis"],"prefix":"10.1111","volume":"38","author":[{"given":"R.","family":"Soenen","sequence":"first","affiliation":[{"name":"Department of Dermatology Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-7467","authenticated-orcid":false,"given":"L.","family":"Schots","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Tilleman","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Biotechnology Ghent University  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Van\u00a0Nieuwerburgh","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Biotechnology Ghent University  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Grine","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Temmerman","sequence":"additional","affiliation":[{"name":"Department of Dermatology AZ Maria Middelares  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4497-8487","authenticated-orcid":false,"given":"T.","family":"Hillary","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Stockman","sequence":"additional","affiliation":[{"name":"Department of Dermatology  AZ Delta, Torhout Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Dreesen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5303-9310","authenticated-orcid":false,"given":"J.","family":"Lambert","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16102"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/dth.14808"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-021-00598-4"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2340\/actadv.v102.206"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2020.1832649"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2019.1630273"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2018.1466022"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.7573\/dic.212266"},{"key":"e_1_2_9_10_1","unstructured":"RIZIV.De TOP 25 van de werkzame bestanddelen in de uitgaven van de verzekering voor geneeskundige verzorging in 2021 \u2010 RIZIV. 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