Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan
Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with on...
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| Autor*in: |
Hamano, Takayuki [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2024 |
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| Anmerkung: |
© The Author(s) 2024 |
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| Übergeordnetes Werk: |
Enthalten in: Advances in therapy - Springer Healthcare, 2000, 41(2024), 4 vom: 16. Feb., Seite 1526-1552 |
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| Übergeordnetes Werk: |
volume:41 ; year:2024 ; number:4 ; day:16 ; month:02 ; pages:1526-1552 |
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| DOI / URN: |
10.1007/s12325-023-02727-3 |
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SPR055270123 |
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| 245 | 1 | 0 | |a Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan |
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| 520 | |a Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764. | ||
| 520 | |a Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. Graphical Abstract | ||
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10.1007/s12325-023-02727-3 doi (DE-627)SPR055270123 (SPR)s12325-023-02727-3-e DE-627 ger DE-627 rakwb eng 610 VZ Hamano, Takayuki verfasserin (orcid)0000-0002-2100-9106 aut Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764. Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. Graphical Abstract Anemia (dpeaa)DE-He213 Chronic kidney disease (dpeaa)DE-He213 Dialysis (dpeaa)DE-He213 Hypoxia-inducible factor prolyl hydroxylase inhibitor (dpeaa)DE-He213 Iron deficiency (dpeaa)DE-He213 Roxadustat (dpeaa)DE-He213 Thromboembolism (dpeaa)DE-He213 Yamaguchi, Yusuke (orcid)0000-0002-8589-5303 aut Goto, Kashia aut Mizokawa, Sho (orcid)0009-0008-4064-4528 aut Ito, Yuichiro (orcid)0000-0002-3117-9328 aut Dellanna, Frank aut Barratt, Jonathan (orcid)0000-0002-9063-7229 aut Akizawa, Tadao (orcid)0000-0002-6150-9201 aut Enthalten in Advances in therapy Springer Healthcare, 2000 41(2024), 4 vom: 16. Feb., Seite 1526-1552 (DE-627)563170433 (DE-600)2421646-X 1865-8652 nnns volume:41 year:2024 number:4 day:16 month:02 pages:1526-1552 https://dx.doi.org/10.1007/s12325-023-02727-3 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 41 2024 4 16 02 1526-1552 |
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10.1007/s12325-023-02727-3 doi (DE-627)SPR055270123 (SPR)s12325-023-02727-3-e DE-627 ger DE-627 rakwb eng 610 VZ Hamano, Takayuki verfasserin (orcid)0000-0002-2100-9106 aut Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764. Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. Graphical Abstract Anemia (dpeaa)DE-He213 Chronic kidney disease (dpeaa)DE-He213 Dialysis (dpeaa)DE-He213 Hypoxia-inducible factor prolyl hydroxylase inhibitor (dpeaa)DE-He213 Iron deficiency (dpeaa)DE-He213 Roxadustat (dpeaa)DE-He213 Thromboembolism (dpeaa)DE-He213 Yamaguchi, Yusuke (orcid)0000-0002-8589-5303 aut Goto, Kashia aut Mizokawa, Sho (orcid)0009-0008-4064-4528 aut Ito, Yuichiro (orcid)0000-0002-3117-9328 aut Dellanna, Frank aut Barratt, Jonathan (orcid)0000-0002-9063-7229 aut Akizawa, Tadao (orcid)0000-0002-6150-9201 aut Enthalten in Advances in therapy Springer Healthcare, 2000 41(2024), 4 vom: 16. Feb., Seite 1526-1552 (DE-627)563170433 (DE-600)2421646-X 1865-8652 nnns volume:41 year:2024 number:4 day:16 month:02 pages:1526-1552 https://dx.doi.org/10.1007/s12325-023-02727-3 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 41 2024 4 16 02 1526-1552 |
| allfields_unstemmed |
10.1007/s12325-023-02727-3 doi (DE-627)SPR055270123 (SPR)s12325-023-02727-3-e DE-627 ger DE-627 rakwb eng 610 VZ Hamano, Takayuki verfasserin (orcid)0000-0002-2100-9106 aut Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764. Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. Graphical Abstract Anemia (dpeaa)DE-He213 Chronic kidney disease (dpeaa)DE-He213 Dialysis (dpeaa)DE-He213 Hypoxia-inducible factor prolyl hydroxylase inhibitor (dpeaa)DE-He213 Iron deficiency (dpeaa)DE-He213 Roxadustat (dpeaa)DE-He213 Thromboembolism (dpeaa)DE-He213 Yamaguchi, Yusuke (orcid)0000-0002-8589-5303 aut Goto, Kashia aut Mizokawa, Sho (orcid)0009-0008-4064-4528 aut Ito, Yuichiro (orcid)0000-0002-3117-9328 aut Dellanna, Frank aut Barratt, Jonathan (orcid)0000-0002-9063-7229 aut Akizawa, Tadao (orcid)0000-0002-6150-9201 aut Enthalten in Advances in therapy Springer Healthcare, 2000 41(2024), 4 vom: 16. Feb., Seite 1526-1552 (DE-627)563170433 (DE-600)2421646-X 1865-8652 nnns volume:41 year:2024 number:4 day:16 month:02 pages:1526-1552 https://dx.doi.org/10.1007/s12325-023-02727-3 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 41 2024 4 16 02 1526-1552 |
| allfieldsGer |
10.1007/s12325-023-02727-3 doi (DE-627)SPR055270123 (SPR)s12325-023-02727-3-e DE-627 ger DE-627 rakwb eng 610 VZ Hamano, Takayuki verfasserin (orcid)0000-0002-2100-9106 aut Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764. Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. Graphical Abstract Anemia (dpeaa)DE-He213 Chronic kidney disease (dpeaa)DE-He213 Dialysis (dpeaa)DE-He213 Hypoxia-inducible factor prolyl hydroxylase inhibitor (dpeaa)DE-He213 Iron deficiency (dpeaa)DE-He213 Roxadustat (dpeaa)DE-He213 Thromboembolism (dpeaa)DE-He213 Yamaguchi, Yusuke (orcid)0000-0002-8589-5303 aut Goto, Kashia aut Mizokawa, Sho (orcid)0009-0008-4064-4528 aut Ito, Yuichiro (orcid)0000-0002-3117-9328 aut Dellanna, Frank aut Barratt, Jonathan (orcid)0000-0002-9063-7229 aut Akizawa, Tadao (orcid)0000-0002-6150-9201 aut Enthalten in Advances in therapy Springer Healthcare, 2000 41(2024), 4 vom: 16. Feb., Seite 1526-1552 (DE-627)563170433 (DE-600)2421646-X 1865-8652 nnns volume:41 year:2024 number:4 day:16 month:02 pages:1526-1552 https://dx.doi.org/10.1007/s12325-023-02727-3 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 41 2024 4 16 02 1526-1552 |
| allfieldsSound |
10.1007/s12325-023-02727-3 doi (DE-627)SPR055270123 (SPR)s12325-023-02727-3-e DE-627 ger DE-627 rakwb eng 610 VZ Hamano, Takayuki verfasserin (orcid)0000-0002-2100-9106 aut Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764. Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. Graphical Abstract Anemia (dpeaa)DE-He213 Chronic kidney disease (dpeaa)DE-He213 Dialysis (dpeaa)DE-He213 Hypoxia-inducible factor prolyl hydroxylase inhibitor (dpeaa)DE-He213 Iron deficiency (dpeaa)DE-He213 Roxadustat (dpeaa)DE-He213 Thromboembolism (dpeaa)DE-He213 Yamaguchi, Yusuke (orcid)0000-0002-8589-5303 aut Goto, Kashia aut Mizokawa, Sho (orcid)0009-0008-4064-4528 aut Ito, Yuichiro (orcid)0000-0002-3117-9328 aut Dellanna, Frank aut Barratt, Jonathan (orcid)0000-0002-9063-7229 aut Akizawa, Tadao (orcid)0000-0002-6150-9201 aut Enthalten in Advances in therapy Springer Healthcare, 2000 41(2024), 4 vom: 16. Feb., Seite 1526-1552 (DE-627)563170433 (DE-600)2421646-X 1865-8652 nnns volume:41 year:2024 number:4 day:16 month:02 pages:1526-1552 https://dx.doi.org/10.1007/s12325-023-02727-3 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 41 2024 4 16 02 1526-1552 |
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Enthalten in Advances in therapy 41(2024), 4 vom: 16. Feb., Seite 1526-1552 volume:41 year:2024 number:4 day:16 month:02 pages:1526-1552 |
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Anemia Chronic kidney disease Dialysis Hypoxia-inducible factor prolyl hydroxylase inhibitor Iron deficiency Roxadustat Thromboembolism |
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Hamano, Takayuki @@aut@@ Yamaguchi, Yusuke @@aut@@ Goto, Kashia @@aut@@ Mizokawa, Sho @@aut@@ Ito, Yuichiro @@aut@@ Dellanna, Frank @@aut@@ Barratt, Jonathan @@aut@@ Akizawa, Tadao @@aut@@ |
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2024-02-16T00:00:00Z |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR055270123</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240325061004.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240325s2024 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s12325-023-02727-3</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR055270123</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s12325-023-02727-3-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Hamano, Takayuki</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-2100-9106</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2024</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. 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Hamano, Takayuki |
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Hamano, Takayuki ddc 610 misc Anemia misc Chronic kidney disease misc Dialysis misc Hypoxia-inducible factor prolyl hydroxylase inhibitor misc Iron deficiency misc Roxadustat misc Thromboembolism Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan |
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610 VZ Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan Anemia (dpeaa)DE-He213 Chronic kidney disease (dpeaa)DE-He213 Dialysis (dpeaa)DE-He213 Hypoxia-inducible factor prolyl hydroxylase inhibitor (dpeaa)DE-He213 Iron deficiency (dpeaa)DE-He213 Roxadustat (dpeaa)DE-He213 Thromboembolism (dpeaa)DE-He213 |
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ddc 610 misc Anemia misc Chronic kidney disease misc Dialysis misc Hypoxia-inducible factor prolyl hydroxylase inhibitor misc Iron deficiency misc Roxadustat misc Thromboembolism |
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ddc 610 misc Anemia misc Chronic kidney disease misc Dialysis misc Hypoxia-inducible factor prolyl hydroxylase inhibitor misc Iron deficiency misc Roxadustat misc Thromboembolism |
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Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan |
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Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan |
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Hamano, Takayuki Yamaguchi, Yusuke Goto, Kashia Mizokawa, Sho Ito, Yuichiro Dellanna, Frank Barratt, Jonathan Akizawa, Tadao |
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risk factors for thromboembolic events in patients with dialysis-dependent ckd: pooled analysis of phase 3 roxadustat trials in japan |
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Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan |
| abstract |
Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764. Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. Graphical Abstract © The Author(s) 2024 |
| abstractGer |
Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764. Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. Graphical Abstract © The Author(s) 2024 |
| abstract_unstemmed |
Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764. Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. Graphical Abstract © The Author(s) 2024 |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR055270123</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240325061004.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240325s2024 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s12325-023-02727-3</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR055270123</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s12325-023-02727-3-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Hamano, Takayuki</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-2100-9106</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2024</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Introduction Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. Methods Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Results Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36–37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52–25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23–15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07–33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82–33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< − 2 fL; adjusted OR 5.55; 95% CI 1.73–17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. Conclusion In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. Trial Registration NCT02780726, NCT02952092, NCT02780141, NCT02779764.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat. 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