Meningococcal Vax Did Not Protect Patients Taking Eculizumab

Janis C. Kelly

July 10, 2017

Eculizumab (Soliris, Alexion Pharmaceuticals), a terminal complement inhibitor used to treat paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome, is linked to a 1000- to 2000-fold increased incidence of invasive meningococcal disease; meningococcal vaccination may not protect patients against this risk. Researchers from the Centers for Disease Control and Prevention (CDC) report this discovery in an article published online July 7 in the Morbidity and Mortality Weekly Report. They note that eculizumab patients may benefit from long-term antimicrobial prophylaxis in addition to use of two types of meningococcal vaccines.

"Because eculizumab recipients remain at risk for meningococcal disease even after receipt of meningococcal vaccines, some health care providers in the United States as well as public health agencies in other countries recommend antimicrobial prophylaxis for the duration of eculizumab treatment; a lifelong course of treatment is expected for many patients," Lucy A. McNamara, PhD, from the CDC's Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, and colleagues, write.

"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."

The new report was based on a February 2017 request from CDC through the Epi-X secure communications network for public health officials that health departments review meningococcal disease cases since 2007 to identify those in eculizumab recipients. The CDC also requested isolates or clinical specimens for additional analysis by the CDC's Bacterial Meningitis Laboratory.

Case–Fatality Ratio of 6%

This request elicited 16 case reports of meningococcal disease in eculizumab recipients during 2008 to 2016. Notably, 11 of 16 were caused by nongroupable Neisseria meningitidis, which the authors explain "is often carried asymptomatically in the nasopharynx [and] rarely causes disease in healthy persons." Eculizumab was being taken for paroxysmal nocturnal hemoglobinuria by 10 of 16 patients, for atypical hemolytic uremic syndrome by five patients, and as part of a clinical trial for another condition by one patient.

All 16 patients had meningococcemia, six had meningitis, and one died (case–fatality ratio, 6%). Average hospitalization was for 6.6 days.

Fourteen of the 16 patients had documented receipt of at least one dose of the quadrivalent meningococcal conjugate (MenACWY) vaccine, and three of the four cases diagnosed after the Advisory Committee on Immunization Practices recommendation that eculizumab recipients receive both MenACWY and the serogroup B (MenB) meningococcal vaccines also had received one or more doses of MenB before disease onset.

Why Vaccination Is Not Enough

"The evidence of meningococcal disease in eculizumab recipients vaccinated against the infecting serogroup, together with the susceptibility of these persons to nongroupable meningococcal strains, is consistent with the in vitro data and suggests that eculizumab therapy interferes with the ability of antimeningococcal antibodies to provide protection against invasive disease," the authors explain.

The CDC report notes that many public health agencies, particularly in the United Kingdom and France, now recommend empiric use of penicillin prophylaxis during eculizumab therapy. Most meningococcal isolates in the United States are fully susceptible to penicillin, the authors write.

New CDC Guidance on What to Watch for in Eculizumab Patients

On the basis of these data, CDC warns healthcare providers that neither vaccination nor antimicrobial prophylaxis are expected to prevent all cases of meningococcal disease in patients taking eculizumab, and that 10 cases in this report had meningococcemia without meningitis.

The authors write, "Although a petechial or purpuric rash is a hallmark of meningococcemia, this rash might not appear until later stages of illness. Initial symptoms of meningococcemia are often relatively mild and nonspecific, and might include fever, chills, fatigue, vomiting, diarrhea, and aches or pains in the muscles, joints, chest, or abdomen; however, these symptoms can progress to severe illness and death within hours. Health care providers should have a high index of suspicion for meningococcal disease in patients taking eculizumab who develop any symptoms consistent with either meningitis or meningococcemia, even if the patient's symptoms initially appear mild, and even if the patient has been fully vaccinated or is receiving antimicrobial prophylaxis."

The authors have disclosed no relevant financial relationships.

Morb Mortal Wkly Rep. Published online July 7, 2017. Full text

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