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How to Know if Methotrexate Is Working for Rheumatoid Arthritis

Medically reviewed by Margaret R. Li, MD, FACR — By Anna Lee Beyer and Elea Carey on September 19, 2022According to the Arthritis Foundation, 1.5 million people in the United States have rheumatoid arthritis. People with rheumatoid arthritis are often prescribed a drug called methotrexate to treat symptoms.

How methotrexate works to treat RA

Methotrexate belongs to a class of drugs called antimetabolites. This type of drug slows the growth of skin cells or cancer cells and suppresses the immune system. In addition to treating rheumatoid arthritis, methotrexate is prescribed to people with severe psoriasis as well as some types of cancer. Also called a disease-modifying antirheumatic drug (DMARD), methotrexate works by reducing pain and swelling. By slowing down disease progression, methotrexate may work to prevent joint damage too. It can take 12 weeks or longer to get the full benefit of methotrexate treatment, but you may start to feel better in just 3 to 6 weeks.

What are the signs that methotrexate is working

Methotrexate is the main drug treatment for rheumatoid arthritis because it’s both effective and tolerable. So, how can you tell if it’s working for you? During the weeks and months after you start treatment, you may notice:decreased painfewer painful jointsless morning stiffnessless swelling in joints How well methotrexate works for you can be affected by your age, sex, ethnicity, genetics, and other health conditions. Your results may also depend on how long you’ve had rheumatoid arthritis and how severe it is.

What to expect when taking methotrexate

Methotrexate comes in tablet form and is taken orally on a schedule prescribed by your doctor, depending on your condition. You may be given a low dose at first with instructions to increase the dose over time. It’s important to follow your doctor’s guidance around the timing and dosing of methotrexate. You may experience these side effects:dizzinessheadachesleepinesspainful, swollen gumsred eyesnot feeling hungryhair lossmouth ulcersloose stoolsfatiguenausea Taking folic acid may reduce common side effects. You should avoid alcohol since the risk of liver damage increases while taking the medication. You should also avoid smoking, as there’s a small chance of lung inflammation. Methotrexate can cause birth defects, so people who are trying to get pregnant should stop taking methotrexate for at least 3 months before trying to conceive. Methotrexate must also be stopped during pregnancy and breastfeeding. If you were assigned female at birth and have been on methotrexate, you should speak with your doctor before trying to conceive. Although low doses of methotrexate are usually well-tolerated, serious side effects are possible. These include: vision changesseizuresconfusionweaknesspassing out Regular blood tests are necessary while on methotrexate because liver or kidney problems can occur as a result of taking the medication. Subtle abnormalities may be detected in the blood work, and your doctor may modify the dosing before a serious problem arises.

Pills vs shots

Methotrexate is also available as an injection, though side effects are typically the same for both the tablet and shot form. With the shot form of the medication, you inject it under the skin on your stomach or thigh. Hypodermic needles or prefilled pens are the methods of delivery. Injectable methotrexate is sometimes prescribed if the pill format doesn’t appear to be working. This form of the medication is also used in people who experience gastric side effects with the pill form. When injected, methotrexate can increase blood levels of the drug, which can lead to improved responses.

How long does it take to feel better on methotrexate

Your symptoms should improve within 3 to 6 weeks of starting a methotrexate regimen. It can take 12 weeks or longer to see the full benefit. When you take methotrexate by mouth, it circulates in your blood for the next 24 hours. However, the real benefit happens as methotrexate builds up in your inflamed joints over time. The uptake of medication into your cells is a slow process, which explains why it may take weeks or months before it’s fully effective. But methotrexate can lower your immune system’s ability to fight infections. Contact your doctor if you develop an infection as severe infections that require hospitalization may be cause for concern.

How long before methotrexate reduces inflammation

Rheumatoid arthritis is an autoimmune or inflammatory disease. That means that your immune system attacks healthy cells causing inflammation. The signs of inflammation are usually swelling and pain. People taking methotrexate typically see improvement in swelling, pain, and signs of inflammation after taking the drug for 12 weeks. By reducing inflammation in joints, methotrexate helps to prevent permanent joint damage. For those taking methotrexate for 3 months or longer and not showing signs of improvement, other medications may be needed.

Lifestyle tips for living with RA

While you’re waiting for relief from your methotrexate regimen, you can talk with your doctor about other ways to find relief from your rheumatoid arthritis symptoms. Regular movement may help. The Centers for Disease Control and Prevention (CDC) recommends people with rheumatoid arthritis do moderate activities like biking, walking, or swimming for 150 minutes per week. The Arthritis Foundation recommends these tips for self-care:Incorporate movement into your day, even if it’s just walking a little farther or gently stretching.During a flare-up, rest to reduce inflammation.Use hot or cold compresses to soothe pain or reduce swelling.Try meditation, massage, acupuncture, or acupressure to reduce stress and pain.Consider taking turmeric or fish oil supplements, which may reduce inflammation.Turn to friends, family, and community for emotional support. Before making any dietary changes or starting supplements, it’s important to speak with your doctor.

The takeaway

Methotrexate is often the first-line treatment to control symptoms of rheumatoid arthritis, reduce inflammation, and prevent permanent joint damage. Your symptoms should improve within 3 to 6 weeks of starting methotrexate, but it could take 12 weeks or longer to see the full benefit. Talk with your doctor about how your symptoms are changing and what you can do to get relief while you wait for methotrexate to take full effect. Last medically reviewed on September 19, 2022

How we vetted this article

SourcesHistoryHealthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. We avoid using tertiary references. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.Baer D. (2018). 11 common questions about taking methotrexate for rheumatoid arthritis.
creakyjoints.org/about-arthritis/rheumatoid-arthritis/ra-treatment/methotrexate-for-rheumatoid-arthritis-questions/Bedoui Y, et al. (2019). Methotrexate: An old drug with new tricks.
ncbi.nlm.nih.gov/pmc/articles/PMC6834162/Friedman B, et al. (2019). Methotrexate mechanism in treatment of rheumatoid arthritis.
ncbi.nlm.nih.gov/pmc/articles/PMC6360124/Methotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo). (nd).
rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/Methotrexate-Rheumatrex-TrexallRheumatoid arthritis. (2020).
cdc.gov/arthritis/basics/rheumatoid-arthritis.htmlRheumatoid arthritis: Causes, symptoms, treatments and more. (2021).
arthritis.org/diseases/rheumatoid-arthritisSingh, JA, et al. (2012). 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis.
onlinelibrary.wiley.com/doi/full/10.1002/acr.21641Understanding methotrexate. (n.d.).
arthritis.org/drug-guide/medication-topics/understanding-methotrexateOur experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Current Version Sep 19, 2022 By Anna Lee Beyer, Elea Carey Edited By Stacey Lastoe Medically Reviewed By Margaret R. Li, MD, FACR Copy Edited By Stassi Myer - CE Nov 26, 2019 By Elea Carey Edited By Frank Crooks VIEW ALL HISTORY Share this articleMedically reviewed by Margaret R. Li, MD, FACR — By Anna Lee Beyer and Elea Carey on September 19, 2022

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