Vaccination’s importance when taking complement inhibitors for MG

Because of a heightened risk of infection, vaccination is very important for people taking complement inhibitors for myasthenia gravis (MG).

In MG, the immune system mistakenly targets proteins involved in nerve-muscle communication, causing problems with movement. This results in characteristic MG symptoms of muscle weakness and fatigue.

Many MG treatments, including medications called complement inhibitors, aim to suppress harmful immune activity to slow damage and ease symptoms. However, this immune suppression increases infection risk in MG, particularly infections that can cause meningitis and related diseases (meningococcal diseases).

While vaccinations for MG patients can’t eliminate infections, they may substantially reduce risks and enhance the safety of MG treatments.

How complement inhibitors affect infection risk

The complement system is a part of the immune system that helps defend the body against infectious agents. However, it also plays a major role in MG-related damage by disrupting specific signaling pathways between nerves and muscles.

Complement inhibitor therapy for MG blocks signaling and activity in the complement system. While this can reduce harmful autoimmunity, it can also dampen protection against infections, making people on complement inhibitors more vulnerable to some diseases.

One of the primary concerns with complement inhibitors is infection with Neisseria meningitidis (N. meningitidis, or meningococcal bacteria), which can cause meningococcal disease. The risk of infection may also be heightened by other bacteria and viruses, including:

• Neisseria gonorrhea (N. gonorrhea), which can cause the sexually transmitted infection gonorrhea
• Streptococcus pneumoniae, which can cause pneumonia
• Haemophilus influenzae type B, which can cause severe infections, particularly in young children

The critical role of meningococcal vaccination

Meningococcal vaccination in MG is crucial when taking complement inhibitors. Some studies estimate that meningococcal disease risk is 1,000 to 2,000 times higher for individuals taking complement inhibitors compared to others.

Infection with N. meningitidis remains possible after vaccination, but the risk is generally lower. Additionally, some meningococcal vaccines appear to protect against other bacteria, including N. gonorrhea.

Which vaccines are recommended and when

Generally, experts recommend most standard, age-appropriate vaccines for MG patients. This includes inactivated vaccines, which use a dead version of the disease-causing germ, and messenger RNA (mRNA) vaccines, which trigger an immune response by making specific proteins.

People taking complement inhibitors should avoid live vaccines, which contain a weakened but still living version of germs.

Meningococcal vaccines

Receiving meningococcal immunization before starting MG treatment is preferred when possible.

U.S. guidelines recommend two meningococcal vaccines, MenACWY and MenB, which are effective against different strains of the bacteria. Each requires multiple shots, with the last taken at least two weeks before starting complement inhibition.

Booster vaccines every five years for MenACWY and every two to three years for MenB can help increase immunity, which may fade over time.

Other vaccines

Other vaccines should typically be given on the standard recommended schedules, including for infants with MG during the first year of life.

People with MG may defer vaccines during symptom flare-ups or while receiving high doses of other immunosuppressant medications, such as corticosteroids. In some cases, it may also be possible to schedule vaccinations around dosing cycles of complement inhibitors.

Some vaccines may require special consideration for people taking complement inhibitors:

• The shingles and seasonal flu vaccines are available in both live and inactivated forms, and only the latter are appropriate.
• The measles, mumps, and rubella (MMR) and yellow fever vaccines are currently only available in live forms and should generally be avoided.

Most people receive the MMR vaccine during early childhood, and the yellow fever vaccine is only required in certain regions.

An analysis of several studies suggests that the benefits of receiving the COVID-19 vaccine and annual boosters generally outweigh the risks for people with MG. The vaccination significantly increased protection against COVID-19, without significantly increasing the risk of MG symptom flare-ups.

What patients should watch for and do

While receiving complement inhibitors, people with MG should:

• wash their hands and follow good personal hygiene habits to avoid infections
• learn to recognize symptoms of infections and report these immediately to their healthcare team
• consider using preventive antibiotic therapies

MG infection prevention can work alongside vaccines and other preventive treatments to help reduce risks.

Identifying potential infections early and treating them promptly can help reduce the risk of developing severe disease. Doctors may recommend carrying emergency antibiotics to take as soon as possible.

People with MG should discuss preventive antibiotic use with their doctors, as recommendations may vary based on factors such as age and other medical conditions. Some people may take preventive antibiotics regularly, while others may use them only in certain situations, such as when traveling to areas with high infection risk.