Clinical Guidance for Managing Meningococcal Disease Risk in Patients Receiving Complement Inhibitor Therapy

Guiding principles

Complement inhibitor therapy increases risk

The risk of meningococcal disease is up to 2,000 times greater for people receiving complement inhibitors compared to otherwise healthy individuals.

Complement inhibitors include:

• C5 inhibitors such as eculizumab and ravulizumab
• Inhibitors of other complement components such as pegcetacoplan and iptacopan

The Food and Drug Administration (FDA)-approved prescribing information for complement inhibitors includes a black box warning for increased meningococcal disease risk. The warning includes a recommendation to administer meningococcal vaccines to patients receiving complement inhibitors.

Substantial risk remains for vaccinated patients

CDC data suggest meningococcal vaccines likely provide incomplete protection against invasive meningococcal disease in people receiving the C5 complement inhibitor eculizumab. Experts believe this increased risk likely also applies to people receiving other C5 inhibitors.

Nongroupable Neisseria meningitidis caused most infections identified in patients receiving eculizumab. Nongroupable N. meningitidis typically doesn't cause invasive meningococcal disease in people with normal immune systems.

Antimicrobial prophylaxis might reduce risk

In addition to vaccination, healthcare providers could consider antimicrobial prophylaxis for complement inhibitor recipients to potentially reduce meningococcal disease risk. However, even with both vaccination and antimicrobial prophylaxis, there’s a substantial risk for meningococcal disease.

Recommendations

Educate patients

Clinicians should ensure all patients receiving complement inhibitors:

• Know the symptoms of meningococcal disease
• Are aware of their increased risk
• Seek care immediately if they start experiencing symptoms
• Receive rapid treatment

Have heightened awareness

Healthcare providers should have a high index of suspicion in patients receiving complement inhibitors with symptoms of meningitis or meningococcemia. This is important even if the patient

• Has symptoms that initially appear mild
• Has been fully vaccinated
• Is receiving antimicrobial prophylaxis

Vaccinate patients

CDC recommends both MenACWY and MenB vaccines for people receiving a complement inhibitor. Ideally, complete or update meningococcal vaccination at least 2 weeks prior to administering the first dose of the complement inhibitor. However, patients can initiate complement inhibitor therapy before meningococcal vaccination has been completed if the risks for delaying completement inhibitor therapy outweigh the risks for developing meningococcal disease.

MenACWY specifics

Initial series: Depending on the brand and age, MenACWY vaccines require 2, 3, or 4 doses

Booster doses: Administer a booster dose of MenACWY vaccine every 5 years, for the duration of complement inhibitor therapy.

Targets: Serogroups A, C, W, and Y; provides no protection against nongroupable N. meningitidis

MenB specifics

Initial series: MenB vaccines require 3 doses

Booster doses: Administer a booster dose of MenB vaccine:

• 1 year after series completion
• Every 2 to 3 years thereafter, for the duration of complement inhibitor therapy

Targets: Serogroup B; cross protection against nongroupable N. meningitidis hasn't been systematically assessed

Resources

Information on conditions treated by complement inhibitors

Atypical hemolytic uremic syndrome (aHUS)

Generalized myasthenia gravis (gMG)

Neuromyelitis optica spectrum disorder (NMOSD)

Paroxysmal nocturnal hemoglobinuria (PNH)

Patient information

Meningococcal disease and people receiving complement inhibitors

Vaccination schedules

For children and adolescents

For adults