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

Article Article scientifique Article Current evidence on the discontinuation of eculizumab in patients with atypical haemolytic uraemic syndrome eng 2017 author Macia Manuel author de Alvaro Moreno Fernando author Dutt Tina author Fehrman Ingela author Hadaya Karine 34570 author Gasteyger Christoph Rolf 94687 author Heyne Nils 310-319 10.1093/ckj/sfw115 28621343 2048-8505 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 Unpublished authors' cases and published cases of eculizumab discontinuation are reviewed.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 Of six unpublished authors' cases, four patients had a subsequent thrombotic microangiopathy (TMA) manifestation within 12 months of discontinuation.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. atypical haemolytic uraemic syndrome discontinuation eculizumab recurrence thrombotic microangiopathy Dewey 617 57 Département de chirurgie 222 false 81 Groupe Iselin Christophe (urologie) 106 Clinical Kidney Journal 10 3 ec143033-b10e-478e-8379-7378aba51b99 Article (Published version) Public sfw115.pdf 428111 application/pdf CC BY-NC openAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Current evidence on the discontinuation of eculizumab in patients with atypical haemolytic uraemic syndrome	Clinical Kidney Journal			2017	521	366

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Gasteyger, Christoph Rolf