dc.contributor.author | de Latour, RP | |
dc.contributor.author | Brodsky, RA | |
dc.contributor.author | Ortiz, S | |
dc.contributor.author | Risitano, AM | |
dc.contributor.author | Jang, JH | |
dc.contributor.author | Hillmen, P | |
dc.contributor.author | Kulagin, AD | |
dc.contributor.author | Kulasekararaj, AG | |
dc.contributor.author | Rottinghaus, ST | |
dc.contributor.author | Aguzzi, R | |
dc.contributor.author | Gao, X | |
dc.contributor.author | Wells, RA | |
dc.contributor.author | Szer, J | |
dc.date.accessioned | 2020-11-27T00:18:58Z | |
dc.date.available | 2020-11-27T00:18:58Z | |
dc.date.issued | 2020-05-24 | |
dc.identifier.citation | de 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.issn | 0007-1048 | |
dc.identifier.uri | http://hdl.handle.net/11343/252421 | |
dc.description.abstract | Ravulizumab, 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.language | English | |
dc.publisher | WILEY | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.title | 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 | |
dc.type | Journal Article | |
dc.identifier.doi | 10.1111/bjh.16711 | |
melbourne.affiliation.department | Medicine and Radiology | |
melbourne.source.title | British Journal of Haematology | |
melbourne.source.volume | 191 | |
melbourne.source.issue | 3 | |
melbourne.source.pages | 476-485 | |
dc.rights.license | CC BY-NC-ND | |
melbourne.elementsid | 1451015 | |
melbourne.contributor.author | Szer, Jeffrey | |
dc.identifier.eissn | 1365-2141 | |
melbourne.accessrights | Open Access | |