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

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

Gérard Socié  1 , Marie-Pierre Caby-Tosi  2 , Jing L Marantz  3 , Alexander Cole  4 , Camille L Bedrosian  5 , Christoph Gasteyger  6 , Arshad Mujeebuddin  4 , Peter Hillmen  7 , Johan Vande Walle  8 , Hermann Haller  9
Affiliations

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

Gérard Socié et al. Br J Haematol. 2019 Apr.

Abstract

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.

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Conflict of interest statement

GS received speaker fees from, and is a consultant for, Alexion Pharmaceuticals, Inc. MPCT is an employee and shareholder of Alexion Europe SAS. JLM and CLB are former employees and current stockholders of Alexion Pharmaceuticals, Inc. AC and AM are employees and stockholders of Alexion Pharmaceuticals, Inc. CG is an employee and shareholder of Alexion Pharma GmbH. PH, JVW and HH received speaker fees and travel reimbursement, and are consultants for Alexion Pharmaceuticals, Inc.

Figures

Figure 1
Figure 1
Rates of meningococcal infection and associated mortality per 100 PY from 2007 to 2016. Data are inclusive of both PNH and aHUS (indications approved in March 2007 and September 2011, respectively). Data expressed as cumulative rate per 100 PY. aHUS, atypical haemolytic uraemic syndrome; PNH, paroxysmal nocturnal haemoglobinuria; PY, patient‐years.
See this image and copyright information in PMC

References

    1. Alatawi, Y.M. & Hansen, R.A. (2017) Empirical estimation of under‐reporting in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Expert Opinion on Drug Safety, 16, 761–767. - PubMed
    1. Andries, G. , Karass, M. , Yandrapalli, S. , Linder, K. , Liu, D. , Nelson, J. , Pawar, R. & Chugh, S. (2017) Atypical hemolytic uremic syndrome in first trimester pregnancy successfully treated with eculizumab. Experimental Hematology & Oncology, 6, 4. - PMC - PubMed
    1. Ardissino, G. , Wally Ossola, M. , Baffero, G.M. , Rigotti, A. & Cugno, M. (2013) Eculizumab for atypical hemolytic uremic syndrome in pregnancy. Obstetrics and Gynecology, 122, 487–489. - PubMed
    1. Ardissino, G. , Salardi, S. , Colombo, E. , Testa, S. , Borsa‐Ghiringhelli, N. , Paglialonga, F. , Paracchini, V. , Tel, F. , Possenti, I. , Belingheri, M. , Civitillo, C.F. , Sardini, S. , Ceruti, R. , Baldioli, C. , Tommasi, P. , Parola, L. , Russo, F. & Tedeschi, S. (2016) Epidemiology of haemolytic uremic syndrome in children. Data from the North Italian HUS network. European Journal of Pediatrics, 175, 465–473. - PubMed
    1. Atkinson, B. , Gandhi, A. & Balmer, P. (2016) History of meningococcal outbreaks in the United States: implications for vaccination and disease prevention. Pharmacotherapy, 36, 880–892. - PubMed

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