Creating a strategy to discontinue eculizumab in patients with atypical hemolytic uremic syndrome (aHUS) is reasonable and safe and improves quality of life, according to research in Blood. The strategy should be based on complement genetics.

Eculizumab has drastically improved outcomes for patients with aHUS. There’s no clearly defined optimal duration of eculizumab treatment in patients with aHUS.

This prospective, multi-center, open-lab phase 4 study assessed the feasibility of eculizumab discontinuation in 55 patients. A total of 19 patients were children younger than 18 years old. A total of 54 patients had received eculizumab for at least 3 to 6 months before inclusion, with a mean duration of 16.5 months.

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In the study, 28 patients had a variant in at least 1 complement gene: 12 in MCP, 6 in CFH, 6 in CFI, 2 in C3 gene, and 2 with combined variants.

A total of 23% of patients had a relapse during follow-up, including 6 children and 7 adults. Of those relapses, 79% were caused by infections. Patients with complement gene variants were at higher risk of aHUS relapse, particularly in carriers of CFH and MCP genes. All 13 patients who relapsed restarted eculizumab. Of these patients, 11 regained their baseline serum creatinine level.

Throughout the study, children did not require eculizumab for a median time of 23.6 months, and adults did not require eculizumab for a median of 24 months. This equated to an estimated cost savings of 32,000 euros.

The presence of a rare variant in a complement gene is the primary determinant of relapse after discontinuing eculizumab for patients with aHUS. The risk of relapse after eculizumab discontinuation was less than 5% in patients with no detected complement gene variant.

The researchers also found that female patients seemed to be at higher risk of relapse than male patients, but an underlying reason was not found. Elevated sC5b-9 levels at discontinuation also indicated a higher risk of relapse. A total 32 patients in the study had elevated sC5b-9 levels at discontinuation. The study included a small patient population, but the predictive validity of sC5b-9 biomarker warrants further study.

Eculizumab discontinuation is feasible in patients with aHUS according to a strategy based on genetics.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Fakhouri F, Fila M, Hummel A, et al. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study. Blood. 2021;137(18):2438-2449. doi:10.1182/blood.2020009280