{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:19:18Z","timestamp":1791389958595,"version":"4.3.3"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006396","name":"Alexion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    To investigate the pharmacokinetics, pharmacodynamics, and exposure\u2013response of the approved 900\/1,200 mg dosing regimen for the terminal complement component 5 (C5) inhibitor eculizumab in patients with generalized myasthenia gravis (gMG).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    The analysis used data from 62 patients aged \u2265 18 years with anti-acetylcholine receptor (AChR) antibody-positive refractory gMG who received eculizumab during the REGAIN study (ClinicalTrials.gov: NCT01997229). One- and two-compartment population-pharmacokinetic models were evaluated, and the impact of covariates on pharmacokinetic parameters was assessed. Relationships between eculizumab exposure and free C5 concentration,\n                    <jats:italic>in vitro<\/jats:italic>\n                    hemolytic activity, clinical response, and tolerability were characterized.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Steady-state serum eculizumab concentrations were achieved by Week 4 and were sustained throughout the 26-week treatment period. The eculizumab pharmacokinetic data were well-described by a two-compartment model with first-order elimination, including effects of body weight on pharmacokinetic parameters and plasma-exchange events on clearance. Complete inhibition of terminal complement was achieved in nearly all patients at the time of trough and peak eculizumab concentrations at all post-dose timepoints assessed (free C5 &amp;lt; 0.5 \u03bcg\/ml in 92% of patients;\n                    <jats:italic>in vitro<\/jats:italic>\n                    hemolysis &amp;lt; 20% in 87% of patients). Serum eculizumab concentrations of \u2265116 \u03bcg\/ml achieved free C5 concentrations of &amp;lt; 0.5 \u03bcg\/ml. Clinical efficacy and tolerability were consistent across the eculizumab exposure range.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Rigorous, quantitative, model-based exposure\u2013response analysis of serum eculizumab concentration and response data demonstrated that the approved eculizumab dosing (900\/1,200 mg) for adults with anti-AChR antibody-positive refractory gMG rapidly achieved complete inhibition of terminal complement activation and provided sustained clinical efficacy across the eculizumab exposure range.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2021.696385","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T13:54:21Z","timestamp":1635861261000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Eculizumab Pharmacokinetics and Pharmacodynamics in Patients With Generalized Myasthenia Gravis"],"prefix":"10.3389","volume":"12","author":[{"given":"Jonathan P. 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