Eculizumab discontinuation in atypical haemolytic uraemic syndrome : TMA recurrence risk and renal outcomes
© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA..
Background: Eculizumab modifies the course of disease in patients with atypical haemolytic uraemic syndrome (aHUS), but data evaluating whether eculizumab discontinuation is safe are limited.
Methods: Patients enrolled in the Global aHUS Registry who received ≥1 month of eculizumab before discontinuing, demonstrated haematologic or renal response prior to discontinuation and had ≥6 months of follow-up were analysed. The primary endpoint was the proportion of patients suffering from thrombotic microangiopathy (TMA) recurrence after eculizumab discontinuation. Additional endpoints included: estimated glomerular filtration rate changes following eculizumab discontinuation to last available follow-up; number of TMA recurrences; time to TMA recurrence; proportion of patients restarting eculizumab; and changes in renal function.
Results: We analysed 151 patients with clinically diagnosed aHUS who had evidence of haematologic or renal response to eculizumab, before discontinuing. Thirty-three (22%) experienced a TMA recurrence. Univariate analysis revealed that patients with an increased risk of TMA recurrence after discontinuing eculizumab were those with a history of extrarenal manifestations prior to initiating eculizumab, pathogenic variants or a family history of aHUS. Multivariate analysis showed an increased risk of TMA recurrence in patients with pathogenic variants and a family history of aHUS. Twelve (8%) patients progressed to end-stage renal disease after eculizumab discontinuation; seven (5%) patients eventually received a kidney transplant. Forty (27%) patients experienced an extrarenal manifestation of aHUS after eculizumab discontinuation.
Conclusions: Eculizumab discontinuation in patients with aHUS is not without risk, potentially leading to TMA recurrence and renal failure. A thorough assessment of risk factors prior to the decision to discontinue eculizumab is essential.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Clinical kidney journal - 14(2021), 9 vom: 06. Sept., Seite 2075-2084 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ariceta, Gema [VerfasserIn] |
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| Links: |
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| Themen: |
Anaemia |
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| Anmerkungen: |
Date Revised 10.03.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1093/ckj/sfab005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM337926662 |
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| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. | ||
| 520 | |a Background: Eculizumab modifies the course of disease in patients with atypical haemolytic uraemic syndrome (aHUS), but data evaluating whether eculizumab discontinuation is safe are limited | ||
| 520 | |a Methods: Patients enrolled in the Global aHUS Registry who received ≥1 month of eculizumab before discontinuing, demonstrated haematologic or renal response prior to discontinuation and had ≥6 months of follow-up were analysed. The primary endpoint was the proportion of patients suffering from thrombotic microangiopathy (TMA) recurrence after eculizumab discontinuation. Additional endpoints included: estimated glomerular filtration rate changes following eculizumab discontinuation to last available follow-up; number of TMA recurrences; time to TMA recurrence; proportion of patients restarting eculizumab; and changes in renal function | ||
| 520 | |a Results: We analysed 151 patients with clinically diagnosed aHUS who had evidence of haematologic or renal response to eculizumab, before discontinuing. Thirty-three (22%) experienced a TMA recurrence. Univariate analysis revealed that patients with an increased risk of TMA recurrence after discontinuing eculizumab were those with a history of extrarenal manifestations prior to initiating eculizumab, pathogenic variants or a family history of aHUS. Multivariate analysis showed an increased risk of TMA recurrence in patients with pathogenic variants and a family history of aHUS. Twelve (8%) patients progressed to end-stage renal disease after eculizumab discontinuation; seven (5%) patients eventually received a kidney transplant. Forty (27%) patients experienced an extrarenal manifestation of aHUS after eculizumab discontinuation | ||
| 520 | |a Conclusions: Eculizumab discontinuation in patients with aHUS is not without risk, potentially leading to TMA recurrence and renal failure. A thorough assessment of risk factors prior to the decision to discontinue eculizumab is essential | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a GFR | |
| 650 | 4 | |a anaemia | |
| 650 | 4 | |a haemoglobin | |
| 650 | 4 | |a thrombosis | |
| 650 | 4 | |a thrombotic microangiopathy | |
| 700 | 1 | |a Fakhouri, Fadi |e verfasserin |4 aut | |
| 700 | 1 | |a Sartz, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Nikolaou, Vasilis |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, David |e verfasserin |4 aut | |
| 700 | 1 | |a Siedlecki, Andrew M |e verfasserin |4 aut | |
| 700 | 1 | |a Ardissino, Gianluigi |e verfasserin |4 aut | |
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