Methotrexate is a common drug used to treat various autoimmune conditions, such as rheumatoid arthritis and psoriasis, by suppressing the overactive immune system. Patients on methotrexate should generally get the annual flu shot because their underlying condition and medication put them at a higher risk for severe influenza complications. However, the drug’s effect on the body’s defenses means there are important considerations regarding the vaccine’s effectiveness and optimal timing, which must be discussed with a prescribing physician.
How Methotrexate Affects the Immune System
Methotrexate (MTX) is classified as an anti-metabolite and works primarily as a folate antagonist, interfering with the body’s use of folic acid. Folate is necessary for the synthesis of nucleotides, the building blocks of DNA and RNA. Methotrexate achieves its immunosuppressive effect by inhibiting the enzyme dihydrofolate reductase (DHFR), which plays a role in the conversion of folate required for DNA replication and cell division.
Because it acts upon rapidly dividing cells, methotrexate primarily affects immune cells, such as T-cells and B-cells, which multiply quickly during an inflammatory response or when generating antibodies after a vaccine. This interference leads to a systemic anti-inflammatory effect, which is beneficial for controlling autoimmune diseases. Patients taking methotrexate are considered immunocompromised, making them more susceptible to serious infections like influenza.
The drug’s action significantly reduces the immune system’s ability to mount a robust defense against pathogens. This suppressed state makes patients high-risk for severe illness, hospitalization, and even death from influenza. While the medication helps manage the underlying disease, it creates a greater need for protective measures like vaccination.
Safety, Efficacy, and Vaccine Types
The standard injectable flu shot, which contains inactivated (killed) virus particles, is considered safe for people taking methotrexate. Because the virus is not alive, it cannot cause the flu or trigger an acute infection in an immunocompromised person. The benefits of receiving the vaccine generally outweigh the risks for this high-risk patient group.
The main concern is not safety but efficacy; methotrexate can reduce the body’s antibody response to the vaccine. The drug blunts the immune system’s ability to recognize antigens and produce protective antibodies. Studies show that patients who continue methotrexate around the time of vaccination may have a significantly lower antibody response compared to those who briefly hold the drug.
This difference in immune response means the protection offered by the flu shot may be less robust than in a healthy individual. Therefore, the distinction between vaccine types is important for patient safety. Patients on methotrexate must strictly avoid the nasal spray vaccine, which contains a live attenuated influenza virus (LAIV). Even though the virus is weakened, there is a theoretical risk that a live vaccine could cause a full infection in someone with a suppressed immune system.
Practical Steps for Optimal Protection
To counteract the reduced efficacy caused by methotrexate, medical professionals may recommend a temporary alteration to the drug schedule around the time of vaccination. The most common strategy involves a short discontinuation of methotrexate after the flu shot to allow the immune system a brief window to generate a more vigorous antibody response.
A large randomized clinical trial demonstrated that holding methotrexate for two weeks immediately following vaccination significantly improved the antibody response from 54.5% to 75.5%. More recent research suggests that a one-week discontinuation may be equally effective in terms of vaccine response while potentially minimizing the risk of a disease flare.
Patients must never unilaterally alter their medication schedule; this decision must be made in consultation with the prescribing physician, such as a rheumatologist. The doctor will weigh the potential for improved vaccine efficacy against the risk of a flare-up of the underlying autoimmune condition. This personalized medical advice is based on the stability of the patient’s disease and their overall health status.
Since a patient’s own immunity may be suboptimal even with optimized timing, additional protective strategies are important. This includes vaccinating household members and close contacts, a strategy known as cocooning, to reduce the overall risk of exposure. Maintaining strict hygiene practices, such as frequent handwashing and avoiding contact with sick individuals, provides another layer of defense.