What to Know About DMARDs for Rheumatoid Arthritis

Disease-Modifying Drugs Approved to Treat RA Joint Damage

Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis, affecting millions of people worldwide annually. RA most often affects the joints, but it can also progress and cause damage to organs such as the skin, eyes, heart, lungs, and kidneys. While there is no cure for RA, there are many medications that work to slow or halt the progression of disease.

Disease-modifying antirheumatic drugs (DMARDs) are an example of medications that have been proven effective in treating RA. This article will review how they work, their dosages, and the potential side effects of the most commonly used DMARDs approved by the Food and Drug Administration (FDA).

What to Know About Disease-Modifying Antirheumatic Drugs (DMARDS)

Verywell / Mayya Agapova

What Are DMARDs?

Despite no definitive cure for RA, there is no lack of options for treatment. Currently there are multiple categories of DMARDs on the market. They work to keep RA activity levels at their lowest possible levels within the body. Some DMARDs can even put the disease into remission.

These treatment categories include conventional DMARDs (cDMARDs), biologic DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs).

While the purpose of all DMARDs is to decrease inflammation, there is not a single means of achieving that goal. Most DMARDs have unique mechanisms and stop inflammation through a variety of ways.

Treatment guidelines consider DMARDs as the primary treatment option for RA.

Tailored Treatment

Given the complexity and intricacies of rheumatoid arthritis, you should consult with your healthcare provider or rheumatologist to develop the most appropriate treatment plan tailored to you.

Most Commonly Used cDMARDs for RA

The most common cDMARDs used in the treatment of RA include but are not limited to:

Read on for a deeper look into each of these medications, their functions, benefits, and potential side effects.

What You Need to Know About Methotrexate

Methotrexate (MTX) is perhaps the oldest and most commonly used cDMARD on the market. Its brand names include Rasuvo, Otrexup, Trexall, and Rheumatrex.

Originally designed to treat certain types of cancers, at much lower doses it is used to treat other conditions, including the autoimmune diseases RA, psoriatic arthritis, and lupus.

In current RA treatment guidelines, MTX is strongly recommended over other DMARDs for patients with moderate-to-severe RA who have not been on any other DMARDs previously.

  • How it works: MTX inhibits dihydrofolate reductase, an enzyme needed for DNA synthesis, as well as down regulating chemical receptors on immune cells.
  • Formulation and frequency: MTX comes in oral pill form or as an injectable, which is used weekly as opposed to daily.
  • How long it takes to start working: Between six to eight weeks.
  • Typical dosages: A typical dose is 12.5–15 milligrams a week, with a maximum dose of 25 milligrams.
  • Potential side effects: Upset stomach, digestive issues, hair loss, mouth sores, headache, and fatigue; more severe side effects include liver injury, scarring of lung tissue, and reduced blood count.
  • Special considerations: Do not take MTX if you are or intend to become pregnant, as it is known to cause birth defects. Men with female partners trying to conceive also need to discontinue MTX prior to conception. While taking MTX you will also need to take a folic acid supplement daily. Alcohol consumption is strongly discouraged while taking MTX.

What You Need to Know About Hydroxychloroquine

Hydroxychloroquine, sold under the brand name Plaquenil, is an antimalarial medication with anti-inflammatory properties, decreasing the swelling and pain associated with RA. It is FDA-approved for use in the treatment of RA and forms of lupus.

  • How it works: While the exact mechanism still remains unknown, it is believed the medication's anti-inflammatory properties and cell communication are due to the inhibition of toll-like receptors, which are responsible for inducing inflammation.
  • Formulation and frequency: Oral pills taken daily.
  • How long it takes to start working: Two to six months.
  • Typical dosages: 200–400 milligrams daily.
  • Potential side effects: Nausea, diarrhea, rash, hair and skin changes, muscle weakness, and, rarely, vision problems.
  • Special considerations: People taking hydroxychloroquine will need to be evaluated by an eye doctor on a regular basis to check for vision issues.

Hydroxychloroquine can be used alone or in combination with other DMARDs.

What You Need to Know About Sulfasalazine

Sulfasalazine, sold under the brand name Azulfidine, can reduce the progression of joint damage. It can be used in combination with methotrexate and hydroxychloroquine, in what is commonly referred to as “triple therapy.”

  • How it works: Like hydroxychloroquine, the exact mechanism of sulfasalazine in RA is still unknown, but the medication does reduce inflammation and sparks action in the immune system.
  • Formulation and frequency: Oral pills taken daily.
  • How long it takes to start working: Six to 12 weeks.
  • Typical dosages: This medication is usually started at a low dose of 500 milligrams and brought up to a maximum of 3,000 milligrams.
  • Potential side effects: Headache, nausea, diarrhea, stomach pain, and sensitivity to the sun.
  • Special considerations: People with a sulfa allergy should not take sulfasalazine. People with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency should consult with their rheumatologist before starting this medication.

What You Need to Know About Leflunomide

Leflunomide, sold under the brand name Arava, is used for the treatment of moderate-to-severe RA. In most cases it appears to be as effective as methotrexate.

  • How it works: Leflunomide helps suppress the immune system, eventually leading to decreased inflammation throughout the body.
  • Formulation and frequency: Oral pills taken daily.
  • How long it takes to start working: Four to eight weeks.
  • Typical dosages: Can be started with or without loading doses and is typically prescribed at 10–20 milligrams per day.
  • Potential side effects: Upset stomach, diarrhea, hair thinning, and liver issues.
  • Special considerations: Women who are trying to conceive should not take leflunomide, as it is known to pose significant risk to the fetus. It should not be used in people with pre-existing liver disease.

Additional DMARD Options

In addition to other treatment options, such as nonsteroidal anti-inflammatories (NSAIDs) and corticosteroids, if conventional DMARDs fail to slow disease progression, your healthcare provider may consider initiating a biologic or target-specific DMARD.

Common bDMARDs used in the treatment of RA include but are not limited to:

  • Humira (adalimumab)
  • Enbrel (etanercept)
  • Remicade (infliximab)
  • Simponi (golimumab)

Newer and common tsDMARDs used in the treatment of RA include but are not limited to:

  • Xeljanz (tofacitinib)
  • Rinvoq (upadacitinib)

Summary

There are various DMARDs available for treating RA, and some work in combination with others. They have different mechanisms, dosages, and side effects, so be sure to discuss your specific case of RA closely with your healthcare provider to get a treatment plan tailored to you.

A Word From Verywell

If you have rheumatoid arthritis and are currently on or thinking of starting DMARD therapy, be sure to speak with your healthcare provider about which treatment options will work best for you. Do not hesitate to mention if your current treatment is not effective or if you are still experiencing joint problems or other symptoms.

If you or your partner plan to become pregnant, discuss alternative treatment options with your physician, as some DMARDs cannot be taken during pregnancy or conception.

Frequently Asked Questions

  • When do you start DMARDs?

    Typically, DMARD therapy is initiated within the first three to six months of disease onset, as it can take several weeks or months before these medications take full effect. Just as each case of RA is different, so is every treatment plan. For that reason, it is crucial to discuss your disease and its severity with your healthcare provider. Your healthcare provider can determine how soon to start you on a DMARD.

  • How do you know which DMARD is best for you?

    Your physician's clinical knowledge coupled with the latest treatment guidelines will determine the best fit for you. For people with moderate-to-severe RA, methotrexate is usually the first-line treatment. For people with low-to-moderate RA, hydroxychloroquine may be initiated first.

  • What are the side effects of DMARD therapy?

    Depending on which DMARD is started, side effects will vary but can include headache, nausea, gastrointestinal issues, diarrhea, rash, photosensitivity, visual changes, as well as changes in liver and kidney function and red or white blood cell counts.

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7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. American College of Rheumatology. Diseases and conditions rheumatoid arthritis. Updated March 2019.

  2. Wasserman A. Rheumatoid arthritis: common questions about diagnosis and management. AFP. 2018;97(7):455-462.

  3. Fraenkel L, Bathon JM, England BR, et al. 2021 american college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924-939. doi:10.1002/acr.24596

  4. Friedman B, Cronstein B. Methotrexate mechanism in treatment of rheumatoid arthritisJoint Bone Spine. 2019;86(3):301-307. doi:10.1016/j.jbspin.2018.07.004

  5. Johns Hopkins Arthritis Center. Rheumatoid arthritis treatment options.

  6. American College of Rheumatology. Hydroxychloroquine(Plaquenil). Updated April 2020.

  7. American College of Rheumatology. Sulfasalazine(Azulfidine). Updated December 2020.