In which patients with atypical HUS would you consider eculizumab discontinuation?

My approach to eculizumab cessation in aHUS is to at least consider cessation in all patients not only given the high cost of the drug, but also given the risk of meningococcemia, which is incompletely protected against by vaccines.

In treating aHUS, I initiate eculizumab (and preventive therapy for meningococcemia) in patients with thrombotic microangiopathy, normal ADAMTS13 activity, renal function (typically creatinine > 2 mg/dL), and no better explanation for these findings. Nearly all patients with aHUS have severe kidney injury and often require hemodialysis. Improvement in renal function is often slow but if renal recovery is complete (normal renal function), I consider cessation. Similarly, if renal function plateaus, then a discussi...

I agree with all the points made by Dr. @Dr. First Last, but would add that genetic information can be useful in informing the discussion. Fakhouri et al recently published prospective data of 55 patients who discontinued eculizumab, 51% of which had complement gene rare variants. Overall, 23% experienced aHUS relapse. Presence of a rare complement gene variant was associated with an increased risk of aHUS relapse, with odds ratio of 16.2, p=0.0135. 11 of 13 patients with relapse recovered their baseline renal function. Similar data regarding predictive value of presense of complement gene variations was shown by Acosta-Medina et al at ASH 2020.