Eculizumab in paraxysmal nocturnal haemogloburinia and atypical haemolytic 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 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

Pregnancy in Women with Atypical Hemolytic Uremic Syndrome

BACKGROUND: Pregnancy outcomes in patients with atypical hemolytic uremic syndrome (aHUS) are not well-documented. Here, we present characteristics of and outcomes for patients with aHUS who became pregnant while enrolled in the Global aHUS Registry. METHODS: The observational Global aHUS Registry (NCT01522183), initiated in April 2012, collects demographics, disease history, treatment, and outcomes data for patients with aHUS, regardless of treatment approach. This descriptive analysis includes patients from the Registry with evaluable pregnancy data supplemented with pharmacovigilance information; the number of pregnancies, outcomes, and exposure to eculizumab were evaluated. RESULTS: As of April 1, 2019, 44 pregnancies were recorded in 41 patients, with 24 pregnancies exposed to eculizumab. Pathogenic variants were identified in 48.8% of patients. Three patients were on dialysis and 6 patients had a kidney graft at the time of pregnancy. Excluding elective terminations, 85.3% of pregnancies resulted in live births. Elective terminations were recorded in 22.7% of pregnancies, miscarriages occurred in 9.1% of pregnancies, and late fetal death in 2.3% of pregnancies. No malformations or anomalies were reported. CONCLUSIONS: Our results show that in women with aHUS, even on dialysis or with a kidney graft, pregnancy is possible with careful monitoring for aHUS flares and prematurity. Prophylactic or therapeutic eculizumab offers disease control with low-risk of fetal abnormalities