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. 2022 Nov 11;9(11):1734.
doi: 10.3390/children9111734.

A Multicenter Study Evaluating the Discontinuation of Eculizumab Therapy in Children with Atypical Hemolytic Uremic Syndrome

Saeed AlZabali  1 , Sawsan AlBatati  1 , Khawla Rahim  1 , Hassan Faqeehi  1 , Abubaker Osman  1 , Abdulaziz Bamhraz  2 , Mohammed A Saleh  3 , Jameela A Kari  4 , Majed Aloufi  5 , Loai Eid  6 , Haydar Nasser  7 , Abubakr Imam  8 , Entesar AlHammadi  9 , Omar Alkandari  10 , Mohammed Al Riyami  11 , Sidharth Sethi  12 , Christoph Licht  13 , Khalid A Alhasan  14   15 , Abdulkarim AlAnazi  1
Affiliations

A Multicenter Study Evaluating the Discontinuation of Eculizumab Therapy in Children with Atypical Hemolytic Uremic Syndrome

Saeed AlZabali et al. Children (Basel). .

Abstract

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA), which has been treated successfully with eculizumab. The optimal duration of eculizumab in treating patients with aHUS remains poorly defined.

Methods: We conducted a multicenter retrospective study in the Arabian Gulf region for children of less than 18 years of age who were diagnosed with aHUS and who discontinued eculizumab between June 2013 and June 2021 to assess the rate and risk factors of aHUS recurrence.

Results: We analyzed 28 patients with a clinical diagnosis of aHUS who had discontinued eculizumab. The most common reason for the discontinuation of eculizumab was renal and hematological remission (71.4%), followed by negative genetic testing (28.6%). During a median follow-up period of 24 months after discontinuation, 8 patients (28.5%) experienced HUS relapse. The risk factors of recurrence were positive genetic mutations (p = 0.020). On the other hand, there was no significant relationship between the relapse and age of presentation, the need for acute dialysis, the duration of eculizumab therapy before discontinuation, or the timing of eculizumab after the presentation. Regarding the renal outcomes after discontinuation, 23 patients were in remission with normal renal function, while 4 patients had chronic kidney disease (CKD) (three of them had pre-existing chronic kidney disease (CKD) before discontinuation, and one case developed a new CKD after discontinuation) and one patient underwent transplantation.

Conclusions: The discontinuation of eculizumab in patients with aHUS is not without risk; it can result in HUS recurrence. Eculizumab discontinuation can be performed with close monitoring of the patients. It is essential to assess risk the factors for relapse before eculizumab discontinuation, in particular in children with a positive complement variant and any degree of residual CKD, as HUS relapse may lead to additional loss of kidney function. Resuming eculizumab promptly after relapse is effective in most patients.

Keywords: HUS relapse; atypical hemolytic uremic syndrome; discontinuation of eculizumab; microangiopathy; thrombotic.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Durations of eculizumab (months) before and after relapse according to the type of gene mutation.
Figure 2
Figure 2
Survival plot for the times to relapse between males and females.
See this image and copyright information in PMC

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