Failure of first meningococcal vaccination in patients with atypical haemolytic uraemic syndrome treated with eculizumab.
Animals
Antibodies, Monoclonal, Humanized
/ adverse effects
Atypical Hemolytic Uremic Syndrome
/ drug therapy
Complement C5
/ antagonists & inhibitors
Complement Inactivating Agents
/ adverse effects
Female
Germany
/ epidemiology
Humans
Incidence
Male
Meningococcal Infections
/ epidemiology
Meningococcal Vaccines
/ therapeutic use
Neisseria meningitidis
/ drug effects
Rabbits
Treatment Failure
Vaccination
Vaccines, Conjugate
/ therapeutic use
atypical haemolytic uraemic syndrome
bactericidal titres
complement inhibition
immunosuppression
meningococcal vaccination
Journal
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
ISSN: 1460-2385
Titre abrégé: Nephrol Dial Transplant
Pays: England
ID NLM: 8706402
Informations de publication
Date de publication:
01 02 2020
01 02 2020
Historique:
received:
19
04
2018
accepted:
13
06
2018
pubmed:
12
7
2018
medline:
12
9
2020
entrez:
12
7
2018
Statut:
ppublish
Résumé
The C5 complement inhibitor eculizumab is a first-line treatment in atypical haemolytic uraemic syndrome (aHUS). Therapy with eculizumab is associated with a highly increased risk for meningococcal infection. Therefore, vaccination is highly recommended before beginning treatment. Efficacy of quadrivalent meningococcal vaccines (MenACWY) in patients treated with the C5 complement inhibitor eculizumab in aHUS has not yet been determined. Patients with aHUS received one dose of a MenACWY conjugate vaccine before eculizumab treatment commenced. Bactericidal titres against meningococcal serogroups A, C, W and Y were determined using baby rabbit complement in 25 patients. Full immune response to meningococcal vaccination was detected in five patients (20%), while seven patients (28%) showed no immune response in any of the tested serogroups. The remaining 13 patients showed incomplete immune response with proof of protective antibody titres for one to three serogroups without perceptible preference for any serogroup. Bactericidal titres after re-vaccination were available for 17 patients. Nine patients with incomplete immune response after first vaccinations showed protective antibody titres for all serogroups after re-vaccination. Kidney function had improved in >50% of patients at the time of re-vaccination compared with the time of first vaccination and immunosuppressive therapy was only applied to re-vaccinated patients following kidney transplantation. Immunogenicity of first quadrivalent meninongococcal vaccination is insufficient in patients with aHUS. Booster response is promising, but incomplete. Therefore, establishing antibiotic prophylaxes seems pivotal.
Sections du résumé
BACKGROUND
The C5 complement inhibitor eculizumab is a first-line treatment in atypical haemolytic uraemic syndrome (aHUS). Therapy with eculizumab is associated with a highly increased risk for meningococcal infection. Therefore, vaccination is highly recommended before beginning treatment. Efficacy of quadrivalent meningococcal vaccines (MenACWY) in patients treated with the C5 complement inhibitor eculizumab in aHUS has not yet been determined.
METHODS
Patients with aHUS received one dose of a MenACWY conjugate vaccine before eculizumab treatment commenced. Bactericidal titres against meningococcal serogroups A, C, W and Y were determined using baby rabbit complement in 25 patients.
RESULTS
Full immune response to meningococcal vaccination was detected in five patients (20%), while seven patients (28%) showed no immune response in any of the tested serogroups. The remaining 13 patients showed incomplete immune response with proof of protective antibody titres for one to three serogroups without perceptible preference for any serogroup. Bactericidal titres after re-vaccination were available for 17 patients. Nine patients with incomplete immune response after first vaccinations showed protective antibody titres for all serogroups after re-vaccination. Kidney function had improved in >50% of patients at the time of re-vaccination compared with the time of first vaccination and immunosuppressive therapy was only applied to re-vaccinated patients following kidney transplantation.
CONCLUSIONS
Immunogenicity of first quadrivalent meninongococcal vaccination is insufficient in patients with aHUS. Booster response is promising, but incomplete. Therefore, establishing antibiotic prophylaxes seems pivotal.
Identifiants
pubmed: 29992261
pii: 5050868
doi: 10.1093/ndt/gfy225
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Complement C5
0
Complement Inactivating Agents
0
MenACWY
0
Meningococcal Vaccines
0
Vaccines, Conjugate
0
eculizumab
A3ULP0F556
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
298-303Informations de copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.