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Current evidence on the discontinuation of eculizumab in patients with atypical haemolytic uraemic syndrome

Publié dansClinical Kidney Journal, vol. 10, no. 3, p. 310-319
Date de publication2017
Résumé

Background. Atypical haemolytic uraemic syndrome (aHUS) is a rare, life-threatening disorder for which eculizumab is the only approved treatment. Life-long treatment is indicated; however, eculizumab discontinuation has been reported. Methods. Unpublished authors' cases and published cases of eculizumab discontinuation are reviewed. We also report eculizumab discontinuation data from five clinical trials, plus long-term extensions and the global aHUS Registry. Results. Of six unpublished authors' cases, four patients had a subsequent thrombotic microangiopathy (TMA) manifestation within 12 months of discontinuation. Case reports of 52 patients discontinuing eculizumab were identified; 16 (31%) had a subsequent TMA manifestation. In eculizumab clinical trials, 61/130 patients discontinued treatment between 2008 and 2015. Median follow-up post-discontinuation was 24 weeks and during this time 12 patients experienced 15 severe TMA complications and 9 of the 12 patients restarted eculizumab. TMA complications occurred irrespective of identified genetic mutation, high risk polymorphism or auto-antibody. In the global aHUS Registry, 76/296 patients (26%) discontinued, 12 (16%) of whom restarted. Conclusions. The currently available evidence suggests TMA manifestations following discontinuation are unpredictable in both severity and timing. For evidence-based decision making, better risk stratification and valid monitoring strategies are required. Until these exist, the risk versus benefit of eculizumab discontinuation, either in specific clinical situations or at selected time points, should include consideration of the risk of further TMA manifestations.

Mots-clés
  • atypical haemolytic uraemic syndrome
  • discontinuation
  • eculizumab
  • recurrence
  • thrombotic microangiopathy
Citation (format ISO)
MACIA, Manuel et al. Current evidence on the discontinuation of eculizumab in patients with atypical haemolytic uraemic syndrome. In: Clinical Kidney Journal, 2017, vol. 10, n° 3, p. 310–319. doi: 10.1093/ckj/sfw115
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Article (Published version)
Identifiants
ISSN du journal2048-8505
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Informations techniques

Création04/07/2017 11:25:00
Première validation04/07/2017 11:25:00
Heure de mise à jour15/03/2023 01:59:45
Changement de statut15/03/2023 01:59:45
Dernière indexation12/02/2024 12:44:47
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