How Does Methotrexate Treat Rheumatoid Arthritis?

Medically Reviewed by David Zelman, MD on September 10, 2022
Written by Susan Bernstein
3 min read

Methotrexate is one of the most effective medications to treat rheumatoid arthritis (RA). It's the first drug most doctors prescribe after you’re diagnosed.

It will help ease symptoms like joint pain, fatigue, redness, and swelling. It may also help prevent damage to your organs and joints.

Methotrexate interrupts the process that causes RA inflammation, which damages your joints and organs over time.

Your doctor may call it a “DMARD,” which is a type of RA drug. (DMARD stands for disease-modifying antirheumatic drug).

You can take methotrexate in either pills or shots. There are prefilled methotrexate shots that are easy to take at home.

You will take 7.5 to 10 milligrams each week. Your doctor may raise that to 20-25 milligrams per week if needed.

The pills will come with directions about how many to take and when. If you’re not sure about those instructions, ask your doctor or a pharmacist.

Shots work better for some people, especially if you forget to take your pills on schedule or if the pills cause nausea. Methotrexate liquid comes in vials with a hypodermic needle or in prefilled pens with various doses.

You inject the drug under the skin on your stomach or thigh. Your doctor or nurse will show you how to do this at home. If you use a prefilled pen, you’ll stick the pen into your stomach or thigh and press on it to inject the drug. Try to give yourself your shot in a different spot each time. This will help you avoid skin reactions.

It can take 3 to 6 weeks to start to feel your methotrexate work. It takes even longer -- 12 weeks -- to get the full effects.

Your doctor will test your blood often to check on how well your treatment works and to make sure it’s safe for organs such as your liver.

Your doctor may prescribe methotrexate alone. Or you may also take other drugs like aspirin, nonsteroidal anti-inflammatory drugs, low-dose steroids, or other DMARDs.

You’ll probably take folic acid supplements along with methotrexate. This vitamin can help you lower your chance of certain side effects.

Talk to your doctor before you take any drug or supplement. Not all drugs mix well. Taking biologics is not recommended while taking methotrexate. 

You may notice these side effects while you take methotrexate:

Tell your doctor if you have them. They can adjust your dose so you feel better. Minor side effects should lessen over time.

This drug can harm your liver. You’ll visit the doctor regularly to check on how methotrexate affects your body. Your doctor might test your liver as often as once a month for the first 6 months you take the drug. After that, you may get a liver test every 3 months.

You’re more likely to get an infection while you take methotrexate. So take these steps to stay well:

  1. Try to avoid people with infections like colds or flu.
  2. Wash your hands regularly.
  3. Tell your doctor if you have fever, chills, or a cough.

Methotrexate can also:

  • Make lymphoma (cancer of the lymphatic system) more likely.
  • Make your skin more sensitive to the sun. Use sunscreen, wear protective clothing, and don’t use sunlamps or tanning beds.
  • Cause birth defects. If you or your partner could get pregnant, you should use birth control while on methotrexate. Men should continue to use protection for 3 months after the last dose. Women should stay on birth control for at least 1 menstrual cycle after the last dose and not breastfeed while taking methotrexate.
  • Cause lung problems, although this is rare. Tell your doctor if you cough frequently or have shortness of breath.