Eculizumab in paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome: 10-year pharmacovigilance analysis

Br J Haematol. 2019 Apr;185(2):297-310. doi: 10.1111/bjh.15790. Epub 2019 Feb 15.


Eculizumab is the first and only medication approved for paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS) treatment. However, eculizumab safety based on long-term pharmacovigilance is unknown. This analysis summarises safety data collected from spontaneous and solicited sources from 16 March 2007 through 1 October 2016. Cumulative exposure to eculizumab was 28 518 patient-years (PY) (PNH, 21 016 PY; aHUS, 7502 PY). Seventy-six cases of meningococcal infection were reported (0·25/100 PY), including eight fatal PNH cases (0·03/100 PY). Susceptibility to meningococcal infections remained the key risk in patients receiving eculizumab. The meningococcal infection rate decreased over time; related mortality remained steady. The most commonly reported serious nonmeningococcal infections were pneumonia (11·8%); bacteraemia, sepsis and septic shock (11·1%); urinary tract infection (4·1%); staphylococcal infection (2·6%); and viral infection (2·5%). There were 434 reported cases of eculizumab exposure in pregnant women; of 260 cases with known outcomes, 70% resulted in live births. Reporting rates for solid tumours (≈0·6/100 PY) and haematological malignancies (≈0·74/100 PY) remained stable over time. No new safety signals affecting the eculizumab benefit-risk profile were identified. Continued awareness and implementation of risk mitigation protocols are essential to minimise risk of meningococcal and other Neisseria infections in patients receiving eculizumab.

Keywords: atypical haemolytic uraemic syndrome; eculizumab; paroxysmal nocturnal haemoglobinuria; pharmacovigilance; safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Atypical Hemolytic Uremic Syndrome / drug therapy*
  • Child
  • Child, Preschool
  • Complement Inactivating Agents / adverse effects*
  • Complement Inactivating Agents / therapeutic use
  • Databases, Factual
  • Fatigue / chemically induced
  • Female
  • Fever / chemically induced
  • Hemoglobins / deficiency
  • Hemoglobinuria, Paroxysmal / drug therapy*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Meningococcal Infections / chemically induced
  • Middle Aged
  • Opportunistic Infections / chemically induced
  • Pharmacovigilance
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Pregnancy Outcome
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Complement Inactivating Agents
  • Hemoglobins
  • eculizumab