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We used a modelling approach to describe the tocilizumab exposure\u2010response relationship and to investigate the different dynamics of the individual components of the routinely used continuous composite measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pharmacokinetic (PK), clinical and laboratory data were obtained from a prospective, observational, single\u2010centre study involving 35 subjects with RA treated with intravenous tocilizumab. A population PK\/pharmacodynamic analysis was performed using nonlinear mixed effects models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The population for model development comprised 1086, 1083 and 1082 observations calculated with the disease activity score based on 28 joint (DAS28) and the simplified and clinical disease activity scores (SDAI, CDAI). The tocilizumab exposure\u2010response relationship was described with an indirect\u2010response model. Two main groups of individual components were identified based on their different dynamics under tocilizumab treatment: (i) tender and swollen joint counts and patient and evaluator global assessment showed a slower decrease of their baseline value (half\u2010life: 4.6\u00a0weeks, RSE: 24%) and the need for higher serum drug concentration (EC<jats:sub>50<\/jats:sub>: 4.60\u00a0\u03bcg\/mL, RSE: 103%, IIV: 359%) than (ii) C\u2010reactive protein and erythrocyte sedimentation rate (half\u2010life: 2.3\u00a0weeks, RSE 19%; EC<jats:sub>50<\/jats:sub>: 0.878\u00a0\u03bcg\/mL, RSE: 41%, IIV: 238%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study confirms a different dynamics of the individual components of the most frequently used continuous composite measures under tocilizumab treatment which should be taken into account to avoid misassessment of disease activity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13954","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T15:46:15Z","timestamp":1554738375000},"page":"1710-1718","source":"Crossref","is-referenced-by-count":13,"title":["Exposure\u2010response modeling of tocilizumab in rheumatoid arthritis using continuous composite measures and their individual components"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-8107","authenticated-orcid":false,"given":"Carla","family":"Bastida","sequence":"first","affiliation":[{"name":"Pharmacy Service, Division of Medicines, Hospital Clinic Barcelona Universitat de Barcelona  Spain"},{"name":"Department of Pharmacy &amp; Pharmacology Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolors","family":"Soy","sequence":"additional","affiliation":[{"name":"Pharmacy Service, Division of Medicines, Hospital Clinic Barcelona Universitat de Barcelona  Spain"},{"name":"IDIBAPS  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Ruiz\u2010Esquide","sequence":"additional","affiliation":[{"name":"Arthritis Unit, Rheumatology Department, Hospital Clinic Barcelona Universitat de Barcelona  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimon","family":"Sanmart\u00ed","sequence":"additional","affiliation":[{"name":"Arthritis Unit, Rheumatology Department, Hospital Clinic Barcelona Universitat de Barcelona  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwin D.R.","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department of Pharmacy &amp; Pharmacology Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Department of Clinical Pharmacy, University Medical Center Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2017-0173"},{"key":"e_1_2_9_3_1","unstructured":"RoActemra\u00ae SPC (Roche registration Limited) 2009.http:\/\/www.ema.europa.eu\/docs\/es_ES\/document_library\/EPAR_\u2010_Product_Information\/human\/000955\/WC500054890.pdf. 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