Eculizumab Linked to High Risk of Meningococcal Disease, Despite Vaccination

Between 2008 and 2016, 16 cases of meningococcal disease were identified in patients on eculizumab therapy (Soliris; Alexion). 

Eculizumab, a complement inhibitor, is indicated for the treatment of paroxysmal nocturnal hemoglobinemia and atypical uremic syndrome. Due to the increased risk for meningococcal disease in patients receiving the drug (1000–2000 fold increase), the Food and Drug Administration (FDA) required a boxed warning in the prescribing information as well as a Risk Evaluation and Mitigation Strategy (REMS) program to  to educate patients and providers.

Patients taking eculizumab are recommended to receive both the quadrivalent meningococcal conjugate (MenACWY) and serogroup B (MenB) meningococcal vaccines as per the Advisory Committee on Immunization Practices (ACIP). Moreover, the use of prophylactic antibiotics (ie, penicillin) during eculizumab therapy has also been recommended by health agencies in other countries. For patients with a penicillin allergy, macrolides are typically recommended. 

A review of the 16 cases of meningococcal disease linked to eculizumab-treated patients showed that eleven were caused by nongroupableNeisseria meningitidis and four were caused by serogroup Y. Fourteen patients had documentation of at least one dose of meningococcal vaccine (MenACWY) prior to disease onset.  

All of the patients (median age 30 years) had meningococcemia with six showing signs of meningitis. The patients were hospitalized for about 6.6 days (range 1–14 days) and one death was reported. Results from antimicrobial susceptibility testing indicated that one patient with a penicillin intermediate-susceptible strain had been prescribed penicillin prophylaxis. 

In vitro data have shown that eculizumab impairs meningococcal killing in whole blood despite patients being vaccinated against the appropriate serogroup. The current vaccines against meningococcal disease only target serogroup-specific proteins and do not provide protection against nongroupable N. meningitidis.

Meningococcal vaccination and antimicrobial prophylaxis cannot be expected to prevent all meningococcal disease in eculizumab users, however the CDC recommends clinicians continue to adhere to ACIP recommendations. The report also urges clinicians to suspect meningococcal disease in patients receiving eculizumab who exhibit symptoms consistent with either meningitis or meningococcemia even if the patients’ symptoms are mild and even if they have been vaccinated or are receiving prophylactic antimicrobials.

“Heightened awareness, early care seeking, and rapid treatment of any symptoms consistent with meningococcal disease are essential for all patients receiving eculizumab treatment, regardless of meningococcal vaccination or antimicrobial prophylaxis status,” concluded lead study author, Lucy A. McNamara, PhD.

For more information visit CDC.gov.