dc.date.accessioned | 2020-07-13T17:54:08Z | |
dc.date.available | 2020-07-13T17:54:08Z | |
dc.date.created | 2020-03-25T12:55:33Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Chowdary, Pratima Carcao, Manuel Holme, Pål Andre Jiménez-Yuste, Victor Lentz, Steven R. Møss, Judi Poulsen, Lone Hvitfeldt Shen, Chunduo Tosetto, Alberto Wheeler, Allison Santagostino, Elena . Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A. Research and Practice in Thrombosis and Haemostasis. 2019, 3(3), 542-554 | |
dc.identifier.uri | http://hdl.handle.net/10852/77830 | |
dc.description.abstract | Background
N8‐GP is an extended half‐life recombinant factor VIII developed for prophylaxis and treatment of bleeds in patients with hemophilia A.
Objective
To assess pharmacokinetic (PK ) characteristics of N8‐GP in previously treated patients with severe hemophilia A, model the time spent at hemophilia thresholds of ≥1 and ≤5 IU/dL (moderate) or >5 IU/dL (mild) FVIII levels during N8‐GP prophylaxis, and investigate the relationship between N8‐GP half‐life and von Willebrand factor (vWF ).
Methods
PK assessments were obtained from patients with severe hemophilia A (FVIII < 1 IU/dL) participating in 4 clinical trials: pathfinder 1 (20‐60 years); pathfinder 2 (12‐17 and ≥18 years); pathfinder 5 (0‐11 years), and pathfinder 7 (25‐71 years). All PK profiles were assessed after washout and considered single‐dose PK profiles. Pre‐ and postdose FVIII activity at steady state was measured at all visits.
Results
From 69 patients, 108 PK profiles of N8‐GP 50 IU/kg were assessed. Adults/adolescents received 50 IU/kg every 4 days, achieving mean trough levels of 3.0 IU/dL (95% confidence interval, 2.6‐3.5, adults) and 2.7 IU/dL (1.8‐4.0, adolescents). Children received 60 IU/kg twice weekly, leading to mean trough levels of 1.2 IU/dL (0.8‐1.6, 0‐ to 5‐year‐olds) and 2.0 IU/dL (1.5‐2.7, 6‐ to 11‐year‐olds). PK modeling predicted children dosed every 3 days and adults/adolescents dosed every 3 to 4 days would maintain FVIII levels >5 and >1 IU/dL for >80% and 100% of the time, respectively. N8‐GP half‐life correlated linearly with von Willebrand factor levels in adults/adolescents, less in children.
Conclusions
Prophylaxis with fixed intervals (Q4D/twice weekly) and fixed weight‐based dosing (50/60 IU/kg) ensured >1 IU/dL FVIII trough levels in both adults and children. | |
dc.language | EN | |
dc.publisher | Wiley Online Library | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A | |
dc.type | Journal article | |
dc.creator.author | Chowdary, Pratima | |
dc.creator.author | Carcao, Manuel | |
dc.creator.author | Holme, Pål Andre | |
dc.creator.author | Jiménez-Yuste, Victor | |
dc.creator.author | Lentz, Steven R. | |
dc.creator.author | Møss, Judi | |
dc.creator.author | Poulsen, Lone Hvitfeldt | |
dc.creator.author | Shen, Chunduo | |
dc.creator.author | Tosetto, Alberto | |
dc.creator.author | Wheeler, Allison | |
dc.creator.author | Santagostino, Elena | |
cristin.unitcode | 185,53,49,11 | |
cristin.unitname | Avdeling for blodsykdommer | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1803455 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Research and Practice in Thrombosis and Haemostasis&rft.volume=3&rft.spage=542&rft.date=2019 | |
dc.identifier.jtitle | Research and Practice in Thrombosis and Haemostasis | |
dc.identifier.volume | 3 | |
dc.identifier.issue | 3 | |
dc.identifier.startpage | 542 | |
dc.identifier.endpage | 554 | |
dc.identifier.doi | https://doi.org/10.1002/rth2.12220 | |
dc.identifier.urn | URN:NBN:no-80984 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2475-0379 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/77830/1/Fixed%2Bdoses%2Bof%2BN8%25E2%2580%2590GP%2Bprophylaxis%2Bmaintain%2Bmoderate%25E2%2580%2590tomild%2Bfactor%2BVIII%2Blevels%2Bin%2Bthe%2Bmajority%2Bof%2Bpatients%2Bwith%2Bsevere%2Bhemophilia%2BA.pdf | |
dc.type.version | PublishedVersion | |