DMARDs for Rheumatoid Arthritis (2022)

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).

DMARDs for Rheumatoid Arthritis (1)

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:

  • Methotrexate
  • Hydroxychloroquine
  • Sulfasalazine
  • Leflunomide

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.

(Video) Biologics and DMARDs treatments of Rheumatoid arthritis

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.

(Video) Rheumatoid Arthritis and DMARDs

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.

    (Video) Methotrexate - Pharmacology (DMARDs, mechanism of action, side effects)

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.

  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 arthritis.Joint 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).

  7. American College of Rheumatology. Sulfasalazine(Azulfidine).

    (Video) Rheumatoid (Part 14): Management (E): TNF DMARDs

(Video) Rheumatoid (part 12) | Management (C) | Hydroxychloroquine and other Synthetic DMARDs

FAQs

Which DMARD is best for rheumatoid arthritis? ›

Methotrexate. Benefits: This is the most commonly prescribed drug for rheumatoid arthritis and one of the most effective for several kinds of inflammatory arthritis. Doctors often use methotrexate in combination with other drugs. Risks: Methotrexate most commonly causes nausea.

What does DMARDs do for rheumatoid arthritis? ›

'DMARD' (pronounced 'dee-mard') stands for disease modifying anti-rheumatic drug. These drugs are usually prescribed early on in the disease by the rheumatology team. They help to slow down the progression of your RA and in doing so can improve the day-to-day symptoms of your disease.

When should DMARDs be started in RA? ›

Guidelines recommend that patients should be referred early, ideally within six weeks of the onset of symptoms,1 and that DMARDs should be started within 12 weeks of onset.

What is the gold standard for rheumatoid arthritis? ›

Even in the current era of biological targeted therapies, MTX remains the initial preferred antirheumatic drug and is considered to be the gold standard for treatment of RA.

What is the most successful drug for rheumatoid arthritis? ›

Methotrexate is usually the first medicine given for rheumatoid arthritis, often with another DMARD and a short course of steroids (corticosteroids) to relieve any pain. These may be combined with biological treatments.
...
The DMARDs that may be used include:
  • methotrexate.
  • leflunomide.
  • hydroxychloroquine.
  • sulfasalazine.

What is the safest drug to treat rheumatoid arthritis? ›

Methotrexate is widely regarded as one of the safest of all arthritis drugs, though it carries some potential downsides. Gastrointestinal symptoms such as nausea and vomiting are its most frequent side effects.

When do you stop using DMARDs? ›

Once patients with rheumatoid arthritis (RA) achieve remission, they can safety discontinue treatment with disease-modifying anti-rheumatic drugs (DMARDs), according to research published in the Annals of Rheumatic Diseases.

How long does it take DMARDs to work? ›

DMARDs generally work well in most people; however, they may take six to 12 weeks to begin to have an effect. Shutting down the inflammatory process which causes inflammatory arthritis can take a long time, but the result of healthy joints will be worth the wait.

How do you permanently treat rheumatoid arthritis? ›

There is no cure for rheumatoid arthritis. But clinical studies indicate that remission of symptoms is more likely when treatment begins early with medications known as disease-modifying antirheumatic drugs (DMARDs).

What is the second line treatment for rheumatoid arthritis? ›

Examples include gold salts, which are active in vitro against mycobacteria,1 and sulfasalazine, a combination of salicylate and sulfapyridine, the only second-line agent specifically developed for the treatment of rheumatoid arthritis2.

What can I take instead of methotrexate? ›

In elderly patients with RA who are unable to tolerate methotrexate, the alternatives are hydroxychloroquine or sulfasalazine for mild-to-moderate disease and cyclosporin or leflunomide for severe disease, given in combination with low-dose oral corticosteroids.

What is the first line treatment for arthritis? ›

First-Line Management: NSAIDS and Corticosteroids

Aspirin is an effective anti-inflammatory for RA when used at high doses, due to the inhibition of prostaglandins. It is one of the oldest NSAIDs used for joint pain.

What is a natural alternative to methotrexate? ›

A 2015 study of 207 patients with rheumatoid arthritis showed that Tripterygium wilfordii Hook F (TwHF), an herb used in Chinese traditional medicine, was superior to methotrexate monotherapy - as either a monotherapy itself or in combination with methotrexate.

Which is safer methotrexate or leflunomide? ›

Patients who took leflunomide were more likely than those who took methotrexate to discontinue treatment but not because of adverse events. There was no significant difference between the leflunomide and methotrexate groups in the likelihood of elevated hepatic transaminase levels or weight loss.

What is the most significant blood test to diagnose rheumatoid arthritis? ›

No blood test can definitively prove or rule out a diagnosis of rheumatoid arthritis, but several tests can show indications of the condition. Some of the main blood tests used include: erythrocyte sedimentation rate (ESR) – which can help assess levels of inflammation in the body.

What drug has the least side effects for rheumatoid arthritis? ›

Rheumatoid Arthritis Drugs With The Least Side Effects

The RA drug with the least side effects is hydroxychloroquine (Plaquenil). “We don't consider it immunosuppressive, and it doesn't cause elevated liver markers or kidney issues like some of the other drugs,” says Dr. Sharmeen.

What is the best medication for rheumatoid arthritis with the least side effects? ›

Hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine) are used for mild rheumatoid arthritis. They are not as powerful as other DMARDs, but they usually cause fewer side effects.

What happens if I don't take medication for rheumatoid arthritis? ›

Without appropriate treatment, chronic pain, disability, and excess mortality are unfortunate outcomes of this disease. RA causes joint damage in 80% to 85% of patients, with the brunt of the damage occurring during the first 2 years of the disease. Left untreated, the risk of mortality is increased.

Will my RA ever go away? ›

There is no cure for rheumatoid arthritis (RA), but remission can feel like it. Today, early and aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) and biologics makes remission more achievable than ever before.

Can vitamin D reverse rheumatoid arthritis? ›

With a vitamin D dose ≤50,000 IU, only serum vitamin D and TJC improved, and with a vitamin D dose> 50,000 IU, the VAS and DAS28 improved. Conclusions: Compared with placebo control interventions, vitamin D supplementation seemed to be an effective intervention for patients with rheumatoid arthritis.

Can I live a normal life with rheumatoid arthritis? ›

80% of sufferers can lead a normal life with the aid of medication. In the past, rheumatoid arthritis meant being condemned to a wheelchair,” says arthritis expert Daniel Aletaha from the Department of Medicine III, (Division of Rheumatology).

Are DMARDs effective? ›

Disease-modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid arthritis (RA) and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage.

Can you have the Covid vaccine if you have rheumatoid arthritis? ›

Don't Worry About Minor Side Effects. Studies have provided reassurance about side effects of the COVID-19 vaccines for people with RA. According to a report published in JAMA in February 2022, data from more than 5,000 people in 30 countries with rheumatic disease has indicated minimal problems after getting the shots ...

What happens if you don't take folic acid with methotrexate? ›

You should take folic acid with methotrexate to help prevent a folate deficiency. Taking methotrexate can lower levels of folate in your body. A folate deficiency can lead to symptoms like upset stomach, low blood cell counts, tiredness, muscle weakness, mouth sores, liver toxicity and nervous system symptoms.

Can you recover from rheumatoid arthritis? ›

There's no cure for rheumatoid arthritis. However, early diagnosis and appropriate treatment enables many people with the condition to have periods of months or even years between flares. This can help them to lead full lives and continue regular employment.

What can make rheumatoid arthritis worse? ›

Certain foods and additives are believed to increase inflammation in the body, such as sugar, saturated fats, trans fats, omega-6 fatty acids, refined carbohydrates, monosodium glutamate (MSG), gluten, aspartame, and alcohol.

How can I reverse my rheumatoid arthritis? ›

Like other forms of arthritis, RA can't be reversed. Even if you show evidence of low inflammation and your joints aren't swollen and tender, your doctor may want you to continue taking some medication to avoid a flare of the disease. With the right combination of treatments, RA can go into remission.

What is the best injection for rheumatoid arthritis? ›

Methotrexate is a drug used to treat rheumatoid arthritis (RA) and and other inflammatory conditions. Nearly 60% of all rheumatoid arthritis patients are currently on or have been on methotrexate. Methotrexate is recommended as the first treatment for RA by the American College of Rheumatology.

What is the best infusion for rheumatoid arthritis? ›

Disease-modifying antirheumatic drugs (DMARDs) are widely regarded as the most effective infusion therapy for rheumatoid arthritis. To reduce inflammation, DMARDs target special proteins in your body or inflammatory chemicals that your body produces on a cellular level.

What is the most effective medication for arthritis? ›

Nonsteroidal Anti-Inflammatory Drugs

NSAIDs are the most effective oral medicines for OA. They include ibuprofen (Motrin, Advil) naproxen (Aleve) and diclofenac (Voltaren, others). All work by blocking enzymes that cause pain and swelling.

What is the latest drug for rheumatoid arthritis? ›

Official answer. The newest drugs for the treatment of rheumatoid arthritis are the Janus kinase (JAK) inhibitors, which are FDA approved under the brand names Rinvoq, Olumiant, and Xeljanz.

Do you take methotrexate for life? ›

This medicine can stay in a woman's body for 6 months after they stop taking it. For men, there is a risk that methotrexate can damage sperm. This can affect the way a baby develops during pregnancy. Women and men wanting to try for a baby need to stop taking methotrexate at least 6 months before trying to conceive.

Why is methotrexate so toxic? ›

It is generally considered to be safe and therefore, it is not unusual to prescribe doses as high as 25 to 30 mg per week in modern rheumatology [6, 7]. Methotrexate toxicity is mainly due to its effects on folate metabolism.

How quickly does rheumatoid arthritis spread? ›

Clinical History. The typical case of rheumatoid arthritis begins insidiously, with the slow development of signs and symptoms over weeks to months. Often the patient first notices stiffness in one or more joints, usually accompanied by pain on movement and by tenderness in the joint.

What triggers rheumatoid arthritis? ›

Rheumatoid arthritis is an autoimmune condition, which means it's caused by the immune system attacking healthy body tissue. However, it's not yet known what triggers this. Your immune system normally makes antibodies that attack bacteria and viruses, helping to fight infection.

What does the Chinese use for arthritis? ›

Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA).

How can I reverse rheumatoid arthritis naturally? ›

20 Remedies for Rheumatoid Arthritis Flare-Ups
  1. Rest and relaxation.
  2. Exercise.
  3. Yoga.
  4. Tai chi.
  5. Acupuncture.
  6. Massage.
  7. Mindfulness.
  8. Support groups.
Mar 6, 2020

Is methotrexate a high risk medication? ›

Methotrexate is a high-alert drug, and extra safeguards are needed whenever it is prescribed, dispensed, and administered, regardless of the setting, dose, or indication for use. While severe harm and fatalities have occurred during hospitalization, many of the adverse outcomes have occurred after discharge.

What is the best DMARD for rheumatoid arthritis? ›

Methotrexate. Methotrexate is now considered the first-line DMARD agent for most patients with RA. It has a relatively rapid onset of action at therapeutic doses (6-8 weeks), good efficacy, favorable toxicity profile, ease of administration, and relatively low cost.

What is the safest DMARD? ›

Hydroxychloroquine is unique in this respect as it has the best safety profile out of all the conventional DMARDs. Compared to other conventional DMARDs, hydroxychloroquine does not increase the risk of severe infections, nor does it cause hepatotoxicity or renal dysfunction.

Who should not take leflunomide? ›

This drug may rarely cause serious (possibly fatal) liver disease. Most cases occur within 6 months of taking this drug. If you already have liver disease (such as hepatitis B or C), leflunomide should not be used.

What works better than methotrexate? ›

Upadacitinib Proves to Be More Effective Than Methotrexate in Patients With RA. Clinical trial result revealed that upadacitinib may be more effective in treating patients with rheumatoid arthritis than the gold standard of care, methotrexate.

Which is safer methotrexate or leflunomide? ›

Patients who took leflunomide were more likely than those who took methotrexate to discontinue treatment but not because of adverse events. There was no significant difference between the leflunomide and methotrexate groups in the likelihood of elevated hepatic transaminase levels or weight loss.

What is the safest biologic for rheumatoid arthritis? ›

The available evidence indicates that Orencia and Kineret have the lowest risk of serious side effects. However, Kineret, which is given as an injection under the skin every day, causes more redness, itching, rash, and pain at the injection site than the other biologics that are given in this way.

What is the new medicine for rheumatoid arthritis? ›

Official answer. The newest drugs for the treatment of rheumatoid arthritis are the Janus kinase (JAK) inhibitors, which are FDA approved under the brand names Rinvoq, Olumiant, and Xeljanz.

What can I take instead of methotrexate for RA? ›

In elderly patients with RA who are unable to tolerate methotrexate, the alternatives are hydroxychloroquine or sulfasalazine for mild-to-moderate disease and cyclosporin or leflunomide for severe disease, given in combination with low-dose oral corticosteroids.

Are DMARDs safer than biologics? ›

Biologics, for the most part, are more potent than traditional DMARDs. The risk of infection while taking biologics is probably higher. This includes the risk of opportunistic infections, such as TB and fungal infections.

How do you permanently treat rheumatoid arthritis? ›

There is no cure for rheumatoid arthritis. But clinical studies indicate that remission of symptoms is more likely when treatment begins early with medications known as disease-modifying antirheumatic drugs (DMARDs).

Who should not take leflunomide? ›

This drug may rarely cause serious (possibly fatal) liver disease. Most cases occur within 6 months of taking this drug. If you already have liver disease (such as hepatitis B or C), leflunomide should not be used.

What RA Med has the least side effects? ›

The RA drug with the least side effects is hydroxychloroquine (Plaquenil). “We don't consider it immunosuppressive, and it doesn't cause elevated liver markers or kidney issues like some of the other drugs,” says Dr. Sharmeen.

How long can you take leflunomide? ›

Leflunomide stays in your system for at least 1-2 years even once you stop it. Your doctor will need to give you special medication to remove leflunomide from your system prior to trying to become pregnant. Therefore, it is very important to discuss pregnancy plans with your rheumatologist.

Do biologics shorten your life? ›

A deadly tradeoff. For some patients, biologic drugs can reduce the need for steroids and other drugs that also have bad side effects. Life expectancy, which can be several years shorter for people with autoimmune diseases such as rheumatoid arthritis, has been increasing in recent decades.

Is a biologic better than methotrexate? ›

Biologics plus methotrexate improved symptoms more than methotrexate alone. Biologics plus methotrexate improved symptoms more than methotrexate alone. Biologics plus methotrexate did not improve symptoms more than biologics alone. Biologics plus DMARDs improved symptoms more than DMARDs alone.

Are we close to finding a cure for rheumatoid arthritis? ›

There is no cure for rheumatoid arthritis (RA), but remission can feel like it. Today, early and aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) and biologics makes remission more achievable than ever before.

Why is my RA getting worse? ›

Added weight puts more stress on inflamed joints, which leads to more pain. Too much fat in your body can release hormones that worsen RA inflammation. Your treatments may not work as well if you're overweight. Exercise daily, and get help from a nutritionist if you struggle to stay at a healthy weight.

Can you live normal life with RA? ›

Many people can live a healthy, active life with RA. For example, disease-modifying antirheumatic drugs (DMARDs) have become an effective and widely available medication for people with RA. These drugs work by suppressing the immune system and minimizing the damage that it does to joint tissue.

Videos

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2. Disease-modifying antirheumatic drugs (DMARDs) Part 1 - Pharmacology
(Dr.G Bhanu Prakash Animated Medical Videos)
3. Introduction to Antirheumatics (DMARDs)
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4. Methotrexate (Rheumatoid Arthritis Drug)
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5. Drug Combo Effective in Managing Early Rheumatoid Arthritis
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6. Disease modifying anti-rheumatic drugs (DMARDs)
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