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dc.contributor.authorde Latour, RP
dc.contributor.authorBrodsky, RA
dc.contributor.authorOrtiz, S
dc.contributor.authorRisitano, AM
dc.contributor.authorJang, JH
dc.contributor.authorHillmen, P
dc.contributor.authorKulagin, AD
dc.contributor.authorKulasekararaj, AG
dc.contributor.authorRottinghaus, ST
dc.contributor.authorAguzzi, R
dc.contributor.authorGao, X
dc.contributor.authorWells, RA
dc.contributor.authorSzer, J
dc.date.accessioned2020-11-27T00:18:58Z
dc.date.available2020-11-27T00:18:58Z
dc.date.issued2020-05-24
dc.identifier.citationde Latour, R. P., Brodsky, R. A., Ortiz, S., Risitano, A. M., Jang, J. H., Hillmen, P., Kulagin, A. D., Kulasekararaj, A. G., Rottinghaus, S. T., Aguzzi, R., Gao, X., Wells, R. A. & Szer, J. (2020). Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies. BRITISH JOURNAL OF HAEMATOLOGY, 191 (3), pp.476-485. https://doi.org/10.1111/bjh.16711.
dc.identifier.issn0007-1048
dc.identifier.urihttp://hdl.handle.net/11343/252421
dc.description.abstractRavulizumab, a novel long-acting complement component 5 (C5) inhibitor administered every 8 weeks (q8w), was non-inferior to eculizumab for all efficacy outcomes in two randomised, open-label, phase 3 trials in C5 inhibitor-naïve (Study 301) and eculizumab-experienced (Study 302) adult patients with paroxysmal nocturnal haemoglobinuria (PNH). This pre-specified analysis characterised ravulizumab pharmacokinetics (PK), pharmacodynamics (PD; free C5 levels), and PD differences between medications (Study 301, n = 246; Study 302, n = 195). Ravulizumab PK parameters were determined using non-compartmental analysis. Serum free C5 was quantified with a Gyros-based fluorescence assay (ravulizumab) and an electrochemiluminescence ligand-binding assay (eculizumab). Ravulizumab PK parameters were numerically comparable in both studies; the median time to maximum concentrations ranged from 2·3 to 2·8 and 2·3 to 2·6 h in studies 301 and 302, respectively. Ravulizumab steady-state serum concentrations were achieved immediately after the first dose and sustained throughout treatment. For ravulizumab, the mean (SD) post hoc terminal elimination half-life was 49·7 (8·9) days. Serum free C5 concentrations <0·5 µg/ml were achieved after the first ravulizumab dose and sustained throughout treatment in both studies. In a minority of patients, free C5 concentrations <0·5 µg/ml were not consistently achieved with eculizumab in either study. Ravulizumab q8w was more consistent in providing immediate, complete, sustained C5 inhibition than eculizumab every-2-weeks in patients with PNH.
dc.languageEnglish
dc.publisherWILEY
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titlePharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies
dc.typeJournal Article
dc.identifier.doi10.1111/bjh.16711
melbourne.affiliation.departmentMedicine and Radiology
melbourne.source.titleBritish Journal of Haematology
melbourne.source.volume191
melbourne.source.issue3
melbourne.source.pages476-485
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1451015
melbourne.contributor.authorSzer, Jeffrey
dc.identifier.eissn1365-2141
melbourne.accessrightsOpen Access


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