Meningococcal Vaccine Does Not Protect Eculizumab Recipients

Meningococcal disease can occur in patients receiving eculizumab, even if they have been vaccinated against the disease, a new study suggests.

Lucy McNamara, PhD, MS, from the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and colleagues published the results of their study in the CDC’s recent Morbidity and Mortality Weekly Report.

Eculizumab is used to treat paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Because it is a terminal complement inhibitor, patients taking the drug may have increased susceptibility to infections. Indeed, studies have shown that patients receiving eculizumab treatment have a 1000 to 2000-fold greater risk of invasive meningococcal disease than the general population have. This has led to the US Food and Drug Administration (FDA) including a black box warning for increased risk of meningococcal disease in the prescribing information for the drug.

In February 2017, the CDC requested that health departments review meningococcal disease cases since 2007, to identify those occurring in patients taking eculizumab.

Dr. McNamara and colleagues identified 16 cases of meningococcal disease in patients receiving eculizumab between 2008 to 2016. They reviewed these case records and discovered that 11 were caused by nongroupable Neisseria meningitides, which is frequently carried asymptomatically in the nasopharynx of healthy individuals and rarely causes disease. According to the investigators, all 16 patients had meningococcemia, 6 had meningitis, and 1 died. The average hospitalization was for 6.6 days, the authors report. In addition, 14 of the patients had documentation of at least 1 dose of meningococcal vaccine before disease onset.

“We felt it was important to promptly report on these cases to make sure patients and doctors know that for people taking eculizumab, meningococcal vaccination cannot be expected to prevent all cases of meningococcal disease,” said Dr. McNamara in an interview with Contagion^®. “We don't want anyone to think that because they were vaccinated against meningococcal disease, they can't get the disease.”

Despite these findings, Dr. McNamara stressed that patients taking eculizumab should continue receiving meningococcal vaccines as recommended, and that their clinicians should also consider providing these patients with antimicrobial prophylaxis for the duration of eculizumab therapy.

She emphasized the need for clinicians to maintain a high index of suspicion for meningococcal disease in any patient receiving eculizumab, even if the patient has been fully vaccinated and/or is taking antibiotic prophylaxis. “I hope our report will help to make clinicians aware of this issue so that they can educate patients and ensure that patients who develop meningococcal disease while taking eculizumab receive prompt treatment.”

According to Dr. McNamara, it is critically important that patients and providers be alert to any signs or symptoms of meningococcal disease, to facilitate prompt treatment. “Symptoms of meningococcal disease can include fever, chills, headache, stiff neck, confusion, vomiting, diarrhea, severe aches and pains, and a rash,” she said, adding that although the symptoms may seem mild initially, they can rapidly progress to severe illness and death without treatment.

Dr. McNamara concluded that she and her colleagues are also “very interested in learning about additional meningococcal disease cases that occur in patients taking eculizumab, and in better understanding how well antibiotic prophylaxis works to prevent meningococcal disease in these patients.”

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.