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How do I know if methotrexate is working for rheumatoid arthritis?

Medically reviewed by Sally Chao, MD. Last updated on May 12, 2021.

Official answer


If methotrexate is working for your rheumatoid arthritis (RA), you should experience fewer severe arthritis symptoms (such as fewer swollen or painful joints) and be able to move and complete day-to-day activities more easily. X-rays of your affected joints should indicate that existing bone or joint damage is not getting worse. Some laboratory values may also improve.

It usually takes three to six weeks after starting methotrexate to see improvement. It may take as long as 12 weeks to feel the maximum effect. If methotrexate is stopped, symptoms may worsen in three to six weeks.

Methotrexate can be used to treat many different diseases. When it is used for RA, it is considered to be in the class of medicines called disease-modifying antirheumatic drugs, or DMARDs. Exactly how methotrexate works to reduce inflammation in RA is not clear.
According to the American College of Rheumatology guidelines for the treatment of RA, methotrexate is the preferred DMARD for both early RA (less than six months of symptoms) and established RA (greater than six months of symptoms). This is because methotrexate is easy to take, well-tolerated and cost-effective, and there is a great deal of data available on its use. Ninety percent of patients with RA are treated with methotrexate sometime during the course of their disease.

At the beginning of treatment, methotrexate is usually used alone (monotherapy). The recommended beginning dose is 7.5 to 12.5 mg by mouth once a week. To obtain the best results, your doctor may increase this dose by 5-mg increments every two to four weeks to a maximum dose of 20 to 30 mg. One in four patients with RA respond to methotrexate monotherapy after six months. If RA is not well-controlled even at the higher doses of methotrexate, then other medications should be tried.

RA arthritis affects 1.3 million Americans. RA occurs when your immune system attacks your own body, causing inflammation and damage. Why this happens is not clear. Many parts of the body can be affected by RA, but the most common damage is to joints, especially the knees and the small joints in the hands and feet. RA can also cause damage to other organs, such as the lungs, eyes and heart.

RA occurs more frequently in women than men. Although RA may develop at any age, it is most commonly diagnosed in individuals between 30 and 50 years of age.

Symptoms of RA vary from person to person. Symptoms can come and go in an unpredictable fashion. Common symptoms include:

  • Fatigue
  • Joint pain, swelling and tenderness
  • Joint stiffness (usually worse in the morning, but improves with activity)
  • Fever
  • Weakness
  • Weight loss

It can sometimes be difficult to diagnose RA, as other immunologic diseases can present with similar symptoms. However, it is important to diagnose and treat RA promptly. Failure to do so may result in permanent damage to joints and bones. This can lead to disfigurement and restricted movement and impair a person's ability to work and perform day-to-day activities. Prompt diagnosis and treatment prevents progression of joint damage in 90 percent of patients.

There is no cure for RA. The goal of treatment is to induce disease remission—relieve symptoms, improve day-to-day function, prevent permanent damage to joints and organs, and prevent disease progression. Methotrexate has demonstrated the ability to do this.

Initial diagnosis and ongoing monitoring of RA involves undergoing X-rays, a physical exam and laboratory tests. At each appointment, your doctor will ask or may have you complete a questionnaire about your symptoms and ability to complete day-to-day activities. These questionnaires are sometimes called a disease activity score or index and, along with laboratory results and X-ray findings, help your doctor determine whether treatment is working.

  1. American College of Rheumatology. Rheumatoid Arthritis. Available at: [Accessed March 25, 2021].
  2. Food and Drug Administration (FDA). Methotrexate. August 2020. Available at:,s016,s017.pdf. [Accessed April 3, 2021].
  3. Singh JA, Saag KG, Bridges Jr. SL, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26. [Accessed March 24, 2021].
  4. Arthritis Foundation. Understanding Methotrexate. Available at: [Accessed March 29, 2021].
  5. Padjen I, Crnogaj MR, Anić B. Conventional disease-modifying agents in rheumatoid arthritis -- a review of their current use and role in treatment algorithms. Reumatologia/Rheumatology. 2020;58(6):390-400. [Accessed March 24, 2021].

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