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

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 28518 patient-years (PY) (PNH, 21016 PY; aHUS, 7502 PY). Seventy-six cases of meningococcal infection were reported (025/100 PY), including eight fatal PNH cases (003/100 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 (118%); bacteraemia, sepsis and septic shock (111%); urinary tract infection (41%); staphylococcal infection (26%); and viral infection (25%). 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 (approximate to 06/100 PY) and haematological malignancies (approximate to 074/100 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