9 Things to Know About Methotrexate for Rheumatoid Arthritis

1. Methotrexate Is a First-Line Treatment for RA

Methotrexate falls into the category of disease-modifying antirheumatic drugs, or DMARDs. These drugs do more than deal with symptoms; they actually slow down progression of the disease.

In addition to being an effective treatment, methotrexate works relatively quickly and has a milder side-effect profile than other medicines used for RA, says Andrew Tenpas, PharmD, a clinical assistant professor of pharmacy practice at Texas A&M University in Kingsville, Texas.

“We have so much experience with methotrexate, and we know it’s effective and safe,” says Bahar Moghaddam, MD, a rheumatologist at Mount Sinai Hospital in New York City.

2. Methotrexate Fights Inflammation

3. Your Doctor Will Determine Your Dose

“It is extremely important to understand that the drug is taken once weekly, not once each day,” Dr. Tenpas says, noting that mistaking this dosage has led to toxicity in some patients.

Methotrexate can also be given by weekly injection. People can give the methotrexate shot to themselves using an auto-injector. Taking the drug this way allows more of it to get into your system without increasing unwanted side effects.

4. Methotrexate Doesn’t Provide Immediate Relief

Because methotrexate doesn’t simply suppress pain symptoms, it may take a while for people to see whether the drug is effective.

For many people, methotrexate alone, once it starts workin, is enough to manage RA symptoms. B

5. Methotrexate Has Some Side Effects

As with many drugs, people can experience unpleasant, and in rare cases dangerous, side effects from methotrexate. If you experience anything that concerns you, be sure to speak with your healthcare provider.

• Gastrointestinal Upset This is the most common side effect for people with RA.
• Mouth Sores Up to a third of people taking methotrexate for RA develop mouth ulcers.

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• Headache and Fatigue Sometimes referred to as “methotrexate fog,” this might occur a day after taking a methotrexate dose.

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• Hair Loss Hair loss or thinning while on methotrexate is slow and is reversed once you stop taking the medication; taking folic acid can also help counteract this effect.
• Rash
• Dizziness

6. You May Be Able to Minimize Those Side Effects

Some side effects from methotrexate result from a drop in folic acid levels in the body. To reduce these effects, doctors generally prescribe folic acid supplements along with the drug.

Many people find taking the oral medicine with food can prevent stomach upset, Tenpas says.

Some experts recommend splitting the dose by taking half in the morning and the other half 12 hours later to ease these gastrointestinal side effects. If that doesn’t help, talk to your doctor about switching from the oral to the injectable version of the drug.

7. Methotrexate Isn’t for Everyone

• Liver disease or cirrhosis
• Alcohol use disorder
• Kidney disease
• Blood disorders
• HIV/AIDS
• People undergoing radiation therapy

Pregnancy Concerns

Methotrexate Can Impact Vaccine Effectiveness

Because methotrexate affects the immune system, researchers have found that it can blunt the effectiveness of certain vaccines.

Anyone who takes methotrexate should work with their physician to discuss their specific drug regimen at the time of any vaccines.

Interactions With Other Medications

8. Methotrexate Can Raise the Risk of Liver Disease

Fortunately, people who take this drug for RA appear to have a lower risk for this than people who take it for some other conditions.

Still, because of the potential for liver problems, regular alcohol use with methotrexate is not considered safe. “People are encouraged to minimize — if not avoid — alcohol consumption,” Tenpas says.

9. Regular Blood Tests Are Needed for Monitoring

Not all of the negative effects of the drug cause noticeable symptoms, which is why routine blood tests are helpful for people taking this medication. Your rheumatologist can make changes to your dose of methotrexate if there is ever a problem.

The Takeaway

• Methotrexate is a mainstay treatment for rheumatoid arthritis, recognized for its ability to slow disease progression and offer symptom relief when used regularly.
• Although methotrexate can take a few weeks to show benefits, many people with RA find it helps manage symptoms effectively over time, often in combination with other therapies if needed.
• Side effects like gastrointestinal issues, mouth sores, and fatigue are common, but these can often be managed by adjustments like taking folic acid, splitting doses, or switching to an injectable form.
• It is crucial to discuss potential drug interactions and vaccine scheduling with your doctor because methotrexate affects the immune system and can interact with other medications, including some antibiotics.