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Model\u2010based characterization of factors affecting the emergence and dissipation of ADAs may inform drug development and\/or improve understanding in clinical practice. This analysis aimed to predict ADA dynamics, including the potential influence of individual covariates, following subcutaneous satralizumab administration. Satralizumab is a humanized IgG2 monoclonal recycling IL\u20106 receptor antagonist antibody approved for treating neuromyelitis optica spectrum disorder (NMOSD). Longitudinal pharmacokinetic (PK) and ADA data from 154 NMOSD patients in two pivotal Phase 3 studies (NCT02028884, NCT02073279) and PK data from one Phase 1 study (SA\u2010001JP) in 72 healthy volunteers were available for this analysis. An existing population PK model was adapted to derive steady\u2010state concentration without ADA for each patient. A mixed hidden Markov model (mHMM) was developed whereby three different states were identified: one absorbing Markov state for non\u2010ADA developer, and two dynamic and inter\u2010connected Markov states\u2014transient ADA negative and positive. Satralizumab exposure and body mass index impacted transition probabilities and, therefore, the likelihood of developing ADAs. In conclusion, the mHMM model was able to describe the time course of ADA development and identify patterns of ADA development in NMOSD patients following treatment with satralizumab, which may allow for the formulation of strategies to reduce the emergence or limit the impact of ADA in the clinical setting.<\/jats:p>","DOI":"10.1002\/psp4.13230","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T05:39:22Z","timestamp":1728452362000},"page":"2171-2184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunogenicity dynamics and covariate effects after satralizumab administration predicted with a hidden Markov model"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0810-4771","authenticated-orcid":false,"given":"Rory","family":"Leisegang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4928-6284","authenticated-orcid":false,"given":"Hanna E.","family":"Silber Baumann","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2287-3406","authenticated-orcid":false,"given":"Si\u00e2n","family":"Lennon\u2010Chrimes","sequence":"additional","affiliation":[{"name":"Roche Products Ltd  Welwyn UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9882-2668","authenticated-orcid":false,"given":"Hajime","family":"Ito","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co.  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