Methotrexate (MTX) is a disease-modifying antirheumatic drug (DMARD) used primarily to treat autoimmune conditions like rheumatoid arthritis and psoriasis, as well as certain forms of cancer. In these conditions, the immune system mistakenly attacks its own tissues, causing inflammation and damage. MTX is designed to intentionally suppress the immune response to control this overactivity. By reducing the overall activity of immune cells, the drug lowers inflammation and slows disease progression, but this action simultaneously increases the patient’s susceptibility to infections.
How Methotrexate Interacts with the Immune System
Methotrexate exerts its primary effect by acting as an antagonist to folic acid, a B vitamin that is necessary for cell growth and division. Specifically, MTX inhibits an enzyme called dihydrofolate reductase (DHFR), which converts dietary folate into its active form. Without this active folate, the construction of DNA and RNA building blocks is significantly impaired.
Immune cells, such as T-cells and B-cells, are among the most rapidly dividing cells in the body, particularly during an immune response. By interfering with their ability to synthesize new DNA, MTX slows the proliferation of these cells. This suppression halts the expansion of the immune system’s attacking forces, leading to an overall reduction in inflammation.
MTX also promotes the accumulation of adenosine, a molecule that acts as a powerful anti-inflammatory signal. Adenosine helps reduce the activation and function of T-cells and B-cells, further contributing to the drug’s immunosuppressive effect. This multi-pronged approach makes MTX an effective treatment for autoimmune disease, but it directly causes the increased risk of infection.
Recognizing Signs of Increased Infection Risk
The most significant consequence of a suppressed immune system is the diminished ability to fight off common pathogens, which requires heightened vigilance from the patient. Any signs of infection should be reported to the prescribing physician immediately, as a rapid response is often necessary. A persistent fever, especially one exceeding 101 degrees Fahrenheit, is a serious sign that requires urgent medical attention.
Patients should also watch for other common infection symptoms such as a new or worsening cough, difficulty breathing, or a severe sore throat. Unexplained chills, night sweats, or a general feeling of being unwell that lasts more than a day also warrant communication with a healthcare provider. Infections of the urinary tract might present as pain or a burning sensation during urination, or the appearance of blood in the urine.
Minimizing Exposure
Practical precautions must become a part of daily life to minimize exposure to infectious agents. Maintaining strict hand hygiene by washing hands frequently with soap and water is an important preventative measure. Patients should actively avoid close contact with anyone who shows symptoms of illness, such as a cold or the flu.
Food Safety
Practicing food safety is also necessary to reduce the risk of certain bacterial infections. This includes avoiding uncooked or unpasteurized foods.
Guidance on Vaccinations and Monitoring While on Methotrexate
Vaccinations require careful planning for individuals taking methotrexate. Non-live, or inactivated, vaccines are generally safe, but their effectiveness may be reduced since the immune system’s antibody response is suppressed. The annual influenza shot and the pneumococcal vaccines, which protect against pneumonia, are strongly recommended for patients on MTX.
Live-attenuated vaccines, which contain a weakened form of the virus, are generally not recommended for people on immunosuppressive drugs. Examples include the Measles, Mumps, and Rubella (MMR) vaccine and the Zoster vaccine for shingles. If a live vaccine is necessary, it typically requires temporarily stopping MTX, often four weeks before and after vaccination, to allow a safe immune response.
Regular Medical Monitoring
Regular medical monitoring, typically involving blood tests, is mandatory to ensure patient safety while on therapy. These tests include a Complete Blood Count (CBC) to monitor white blood cell and platelet levels, as MTX can affect bone marrow function. Liver Function Tests (LFTs), such as AST and ALT levels, are also performed to check for potential liver toxicity. Initially, blood tests are done frequently until a stable dose is reached, after which monitoring usually continues every one to three months. This allows the healthcare team to adjust the MTX dosage if adverse effects or signs of toxicity appear.