Eculizumab for adult patients with atypical haemolytic-uraemic syndrome: full dataset analysis of Japanese post-marketing surveillance

J Nephrol. 2024 Nov;37(8):2181-2190. doi: 10.1007/s40620-024-01921-y. Epub 2024 May 29.

Abstract

Background: Eculizumab has been approved for atypical haemolytic-uraemic syndrome (aHUS) in Japan since 2013. Post-marketing surveillance enrolled patients with aHUS who received ≥ 1 dose of eculizumab to assess eculizumab safety and effectiveness.

Methods: We evaluated serious adverse events and effectiveness endpoints, i.e., haematologic normalization, a decrease of ≥ 25% in serum creatinine (sCr) levels, and complete thrombotic microangiopathy (TMA) response in adult patients with aHUS without other underlying diseases. In addition, the difference of baseline characteristics between patients who did and did not meet effectiveness endpoints was examined.

Results: In this safety and effectiveness analysis, 79 adult patients were included; median age was 54.0 years, median treatment duration was 30 weeks. Total exposure time of eculizumab was 75.51 patient-years, and 94 serious adverse events were reported in 39 patients. No unexpected safety signals were identified in this population. Mean platelet count, lactate dehydrogenase and estimated glomerular filtration rate significantly improved after 7 days of treatment. Complete TMA response, haematologic normalization and the improvement of sCr levels were met by 35.3%, 40.4% and 51.3% of patients, respectively. Median treatment duration was shorter in patients who did not achieve complete TMA response (6 weeks) than in patients who did (114 weeks). Multivariate analysis suggested that the time from the most recent TMA episode to start of eculizumab treatment was negatively associated with kidney function improvement.

Conclusions: No unexpected safety signals of eculizumab were identified in Japanese patients with aHUS in a real-world setting. Renal outcomes were negatively associated with the time from the most recent TMA episode to the initiation of eculizumab treatment.

Keywords: Atypical haemolytic uraemic syndrome; Eculizumab; Post-marketing surveillance; Thrombotic microangiopathy.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Atypical Hemolytic Uremic Syndrome* / drug therapy
  • Complement Inactivating Agents / adverse effects
  • Complement Inactivating Agents / therapeutic use
  • Creatinine / blood
  • East Asian People
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Japan
  • L-Lactate Dehydrogenase / blood
  • Male
  • Middle Aged
  • Platelet Count
  • Product Surveillance, Postmarketing*
  • Time Factors
  • Treatment Outcome

Substances

  • eculizumab
  • Antibodies, Monoclonal, Humanized
  • Creatinine
  • Complement Inactivating Agents
  • L-Lactate Dehydrogenase