Discontinuation of the terminal complement inhibitor eculizumab in patients with atypical hemolytic uremic syndrome (aHUS) appears to be safe with close patient monitoring and re-treatment in cases of thrombotic microangiopathy (TMA) recurrence, according to study results presented by Noor Dhaliwal, a medical student at the University of Delhi, New Delhi, India, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

“[Terminal complement inhibition with] eculizumab is highly effective and leads to rapid and sustained improvement in renal function and hematological parameters, [with indefinite treatment as] the standard of care,” said Ms Dhaliwal.

However, patient nonadherence and discontinuation is common, and recent evidence suggests that patients with aHUS may safely discontinue therapy. Due to these recent findings, Ms Dhaliwal and colleagues evaluated outcomes, including relapse rate and renal function, of a physician-directed eculizumab discontinuation and monitoring protocol in a prospective cohort study of patients with aHUS conducted at Johns Hopkins University in Baltimore, Maryland.

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The study included 32 consecutive patients with aHUS who were enrolled in the Hopkins Complement Associated Disease Registry and initiated eculizumab therapy between January 2014 and December 2019 due to an acute episode of TMA. The median age at first aHUS diagnosis was 44 years (interquartile range, 25-53.5), and 78.1% of the cohort were women.

In total, 25 patients (78%), who had a median duration on eculizumab therapy of 2.37 months, discontinued therapy; 18 patients (72%) discontinued per protocol under physician direction, and 7 patients (28%) discontinued due to nonadherence. The remaining 6 study patients (18%) continued therapy (1 patient died during a first episode of aHUS).

After therapy discontinuation, the overall relapse rate was 20.0% (5/25). The relapse rate was higher among patients who were nonadherent compared with those who followed the physician-directed cessation protocol (42.8% vs 11.1%; P =.074). Most patients were successfully re-treated and achieved remission again with eculizumab without renal function decline (4/5; 80%); however, 1 patient died in the setting of nonadherence.

From the date of discontinuation to the most recent follow-up, patients who discontinued therapy did not experience significant decline in mean estimated glomerular filtration rate (eGFR, 47.09±28.28 mL/min/1.73 m2 vs 56.95±28.02 mL/min/1.73 m2, respectively; one-sided t test P =.987).

“Eculizumab discontinuation with close monitoring is safe in the majority of patients with [aHUS],” concluded Ms Dhaliwal, “and relapse rates are low with effective salvage with eculizumab re-treatment in the event of recurrence.”

Limitations of the study included small sample size, a limited number of events, and a lack of data for complement gene variants. Larger, multicenter prospective studies are needed to confirm the study results.

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Dhaliwal N, Hussain S, Harshvardhan Upreti H, et al. Outcomes of a clinician-directed protocol for discontinuation of complement inhibition therapy in atypical hemolytic uremic syndrome. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 379. 

This article originally appeared on Hematology Advisor