{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T14:22:10Z","timestamp":1782829330725,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015661","name":"UCB Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Systemic lupus erythematosus (SLE) is a systemic, autoimmune disease characterized by chronic inflammation and organ damage. Dapirolizumab pegol inhibits CD40 ligand (CD40L) and is currently undergoing phase 3 trials for the treatment of SLE. To describe the pharmacokinetic characteristics of dapirolizumab pegol and the relationship between exposure and probability of achieving a British Isles Lupus Assessment Group\u2010based Composite Lupus Assessment (BICLA) response, a population pharmacokinetic (popPK) model and an exposure\u2010response model were developed, based on results of the phase 2b trial (RISE; NCT02804763) of dapirolizumab pegol in SLE. Dapirolizumab pegol pharmacokinetics were found to be dose proportional and well described by a 2\u2010compartment model with first\u2010order elimination from the central compartment. In the popPK model, body weight was the only significant covariate. The average concentration of dapirolizumab pegol, derived from the popPK model, was incorporated into the exposure\u2010response model. Overall, the exposure\u2010response model showed that treatment with dapirolizumab pegol increased the probability of transitioning from BICLA \u201cNonresponder\u201d to \u201cResponder.\u201d No significant covariates on BICLA responder status were identified. Notably, the half maximal effective concentration was greater for the transition from \u201cResponder\u201d to \u201cNonresponder\u201d (150 \u00b5g\/mL) than the transition from \u201cNonresponder\u201d to \u201cResponder\u201d (12 \u00b5g\/mL), indicating that sustained dapirolizumab pegol concentrations may be required to maintain BICLA response. In conclusion, dapirolizumab pegol pharmacokinetics were as expected for a PEGylated molecule and results from the exposure\u2010response model indicate that a favorable dapirolizumab pegol effect was identified for both BICLA \u201cNonresponder\u201d to \u201cResponder\u201d and \u201cResponder\u201d to \u201cNonresponder\u201d transition probabilities.<\/jats:p>","DOI":"10.1002\/jcph.2188","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T12:52:37Z","timestamp":1669899157000},"page":"435-444","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Population Pharmacokinetics and Exposure\u2010Response for Dapirolizumab Pegol From a Phase 2b Trial in Patients With Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"63","author":[{"given":"Chayan","family":"Acharya","sequence":"first","affiliation":[{"name":"Pharmetheus  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats O.","family":"Magnusson","sequence":"additional","affiliation":[{"name":"Pharmetheus  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Vajjah","sequence":"additional","affiliation":[{"name":"UCB Pharma  Slough UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Oliver","sequence":"additional","affiliation":[{"name":"UCB Pharma  Slough UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miren","family":"Zamacona","sequence":"additional","affiliation":[{"name":"UCB Pharma  Slough UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.39"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215089"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218272"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2018.1538789"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.080214"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203318786436"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0235-5"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb06048.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2011.02.005"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102668"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916930400002386"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001001"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2018.12.005"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.1.2"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab381"},{"key":"e_1_2_11_17_1","unstructured":"A Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants With Moderately to Severely Active Systemic Lupus Erythematosus (PHOENYCS GO). 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