Eculizumab discontinuation in atypical haemolytic uraemic syndrome: TMA recurrence risk and renal outcomes

Gema Ariceta; Fadi Fakhouri; Lisa Sartz; Benjamin Miller; Vasilis Nikolaou; David Cohen; Andrew M Siedlecki; Gianluigi Ardissino

doi:10.1093/ckj/sfab005

Eculizumab discontinuation in atypical haemolytic uraemic syndrome: TMA recurrence risk and renal outcomes

Clin Kidney J. 2021 Jan 24;14(9):2075-2084. doi: 10.1093/ckj/sfab005. eCollection 2021 Sep.

Authors

Gema Ariceta¹, Fadi Fakhouri², Lisa Sartz³, Benjamin Miller⁴, Vasilis Nikolaou⁵, David Cohen⁶, Andrew M Siedlecki⁷, Gianluigi Ardissino⁸

Affiliations

¹ Department of Pediatric Nephrology, Vall d'Hebron Hospital, and the Autonomous University of Barcelona, Barcelona, Spain.
² Department of Nephrology and Immunology, CHU de Nantes, Nantes, France.
³ Department of Pediatrics, Skane University Hospital, Lund University, Lund, Sweden.
⁴ Alexion Pharmaceuticals, Inc., Boston, MA, USA.
⁵ Parexel International Ltd, Uxbridge, UK.
⁶ Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, NY, USA.
⁷ Department of Internal Medicine, Renal Division, Brigham and Women's Hospital, Boston, MA, USA.
⁸ Centro per la Cura e lo Studio della Sindrome Emolitico-Uremica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Abstract

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.

Keywords: GFR; anaemia; haemoglobin; thrombosis; thrombotic microangiopathy.