Disease-Modifying Antirheumatic Drugs (DMARDS)

What are DMARDs?

Disease-modifying antirheumatic drugs (DMARDs) are a group of medications that decrease inflammation and pain.

They are often called immunosuppressants or immunomodulators because these medications hold back or change how your immune system — your body’s defense system — works.

What do DMARDs do?

DMARDs:

• Decrease pain and inflammation.
• Reduce or prevent joint damage and bone erosion.
• Slow the speed and spread of disease.
• Preserve joint function.

What diseases do DMARDs commonly treat?

DMARDs are most commonly known for treating rheumatoid arthritis, but also treat:

• Ankylosing spondylitis.
• Psoriatic arthritis.
• Systemic lupus erythematosus.
• Juvenile idiopathic arthritis.
• Systemic sclerosis.
• Multiple sclerosis.
• Sjögren’s syndrome.
• Inflammatory myositis.
• Rheumatoid vasculitis.
• Uveitis.
• Inflammatory bowel disease.
• Crohn’s disease.
• Some cancers.

How do DMARDs work?

DMARDs work in several different ways. All work to hold back your body’s immune system. In an autoimmune disease, such as rheumatoid arthritis, your body’s immune system goes awry. Instead of attacking a foreign invader (such as an infection), it mistakenly attacks your body’s healthy tissues.

DMARDs work by:

• Reducing your immune system’s response to attacking its healthy tissues (most broadly).
• Targeting a specific pathway of your body’s immune system response.
• Working on individual immune system proteins.

What are the types of DMARDs?

There are two main groups of DMARDs, traditional DMARDs and biologics.

Traditional DMARDs

These are the older traditional or conventional DMARDs. Your provider may prescribe one of these medications first. Examples that represent this group include:

• Methotrexate (Rheumatrex®, Trexall®). Many providers start treatment with this medication, then may add others.
• Sulfasalazine (Azulfidine®).
• Hydroxychloroquine (Plaquenil®).
• Leflunomide (Arava®).
• Azathioprine (Imuran®).

Biologics

Biologics are DMARDs that are made using molecular biology. They are made up of proteins. Biologic DMARDs target specific molecules, cells and pathways that cause inflammation and damage tissue. They are more effective than traditional DMARDs.

Your provider may prescribe a biologic if your disease and symptoms didn’t improve on a traditional DMARD or if you had bothersome or serious side effects to those drugs.

There are subcategories of biologics. All target a specific molecule involved in inflammation and joint destruction.

Biologic DMARDs include:

• Tumor necrosis factor (TNF) inhibitors: Examples include etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), certolizumab pegol (Cimzia®), golimumab (Simponi®).
• Interleukin-1 inhibitor: An example is anakinra (Kineret®).
• Interleukin-6 inhibitors: Examples include tocilizumab (Actermra®) and sarilumab (Kevzara®).
• T-cell inhibitor: An example is abatacept (Orencia®).
• B-cell inhibitor: An example is rituximab (Rituxan®).
• Janus kinase inhibitors: These medications are also called biosimilars. (These drugs are similar, but not identical, to existing biologics.) Examples include tofacitinib (Xeljanz®), baricitinib (Olumiant®) and upadacitinib (Rinvoq®).

How are DMARDs taken?

Traditional DMARDs are usually taken by mouth (orally). Biologic DMARDs are given by injection (shot) or infusion (IV into a vein). The exception is the Janus kinase inhibitor biologics. These medications come in pill form and are taken by mouth.

How soon do DMARDs begin to work?

You won’t get immediate pain and inflammation relief when you first take DMARDs. Traditional DMARDs can take a month or more to start working. Biologics and Janus kinase inhibitors usually begin to work after several weeks for some and four to six weeks for others.

How will my healthcare provider choose which DMARD is best for me?

You and your healthcare provider will discuss many factors before deciding if a DMARD is an option for your condition.

Some factors include:

• How active and severe your disease is.
• The side effects of DMARD(s).
• The expected benefits of the DMARD.
• Other medical conditions you currently have or have had.
• Other medications you are currently taking.
• Your general health. Your provider will especially want to know if you’ve had tuberculosis; hepatitis B or C; cancer; or any heart, kidney or liver problems.
• Your personal preference (cost of DMARD, how the DMARD is taken, how often it’s taken and how often you’ll need checkups).

Your healthcare provider may also ask you if:

• You have allergies to other drugs.
• What vaccines you’ve had.
• You are planning to become pregnant. Some DMARDs can harm your fetus.
• You drink alcohol regularly. Some DMARDs can cause liver damage.
• You take supplements, herbal products, vitamins, over-the-counter and other prescription drugs. Some products may interfere with DMARDs.

How are DMARDs prescribed?

Your healthcare provider may prescribe DMARDs as:

• A single traditional DMARD.
• A single traditional DMARD combined with a low-dose corticosteroid, such as prednisone or cortisone, or other drugs.
• Two or more traditional DMARDs in combination.
• A traditional DMARD in combination with a biologic DMARD.

Your healthcare provider may start you on a traditional DMARD if you have mild to moderate disease. If your disease and symptoms don’t improve enough after a few months, your provider may increase the dosage or may switch to a different DMARD or add one or more DMARDs including a biologic DMARD to your treatment plan.

You and your provider will work together to find the best DMARD or combination of medications that work the best and have the fewest side effects.

How will my healthcare provider check me while I’m taking DMARDs?

Before starting a DMARD, your healthcare provider may:

• Test you for tuberculosis and hepatitis B and C.
• Conduct a pregnancy test if you're of childbearing age. You may need to take contraception while taking some DMARDs. Some can harm a fetus. You and your provider will thoroughly discuss your pregnancy plans and the best choice of therapy.

Before you start treatment and while you’re taking DMARDs, you’ll also:

• Have blood tests. These tests help your provider check that these drugs are working as they should and not affecting your organs, especially your liver and kidneys. Your blood test includes a complete blood count and lipid panel.
• Imaging tests to check on the effects of these medications on your joints if you have inflammatory joint disease.

Your provider may order other tests depending on the specific DMARD you are taking. DMARDs have some side effects that are unique to each medication. In general, your provider will check you at least twice a year and perhaps more often for certain tests.

The results help your provider decide if they need to change your dose, change to a different DMARD, add another DMARD to your treatment plan or stop a DMARD.

What are the side effects of DMARDs?

Side effects depend on the type of DMARD you are taking. Each DMARD has some side effects that are unique to it.

Common side effects of traditional DMARDs include:

• Loss of appetite.
• Nausea.
• Diarrhea.
• Abdominal pain.
• Rash, allergic reaction.
• Liver problems.
• Increased risk of infections.
• Low white cell count (leukopenia), red blood cell count (anemia) and platelet count (thrombocytopenia).

Common side effects of biologic DMARDs include:

• Increased risk of common and serious bacterial, fungal and viral infections.
• Reactivation of tuberculosis, herpes zoster, hepatitis B and C.
• Increase in cholesterol levels, low blood cell counts and increased liver enzymes.
• Increased risk of blood clotting (Janus kinase inhibitors).

Many more side effects are sometimes seen with DMARDs. Many are specific to an individual DMARD. You and your provider will discuss all side effects that are possible for the medications that may be options for you. Once you start treatment, never hesitate to talk with your provider if you develop a side effect that bothers you.

Some DMARDs can cause serious side effects in some people. This is one reason why your provider wants to check your blood on a regular, ongoing basis.

Who shouldn’t take DMARDs?

You shouldn’t take DMARDs — especially biologic DMARDs — if:

• You have an active infection.
• You have a low level of stem cells in your bone marrow.
• You have a low white blood cell count (leukopenia).
• You have certain blood cancers, kidney, liver or heart conditions.
• You have immunodeficiency disorders. These are disorders that keep your body from fighting infections and diseases.

Your healthcare provider will carefully collect and review your medical history and the results of tests to make sure DMARDs are an appropriate treatment option for you.

What outcome should I expect from taking DMARDs?

Your healthcare provider can best answer this question. Your specific disease, how severe it is, your other health issues, the specific DMARD(s) you’re taking, and other medications you’re taking are all factors.

In general, DMARDs are a major treatment advance, especially for inflammatory autoimmune diseases such as rheumatoid arthritis. Biologic DMARDs are even more precise than traditional DMARDs in targeting disease.

DMARDs don’t cure or prevent disease. There is also a risk of serious side effects. But you are more likely to achieve a better outcome on DMARDs than on older generation medications.

Moving forward, scientists are working on how to better pair medications with your genetic profile (an approach called precision medicine or personalized medicine). This will allow the best possible outcome with the fewest side effects.

What questions should I ask my healthcare provider about DMARDs?

Be sure to ask:

• What are the benefits and risks of the DMARD(s)?
• What are the possible side effects?
• What side effects should I watch for and call right away if they happen?
• What dose will I be taking and how many times a day will I take this DMARD?
• Is the DMARD that I’ll be taking taken by mouth, injection or IV?
• How often will blood tests and other tests be needed?
• How do my other health conditions, current medications and drug allergies affect DMARD choice?
• How long will I need to take this DMARD?
• What should I do if I want to become pregnant?
• What outcome should I expect if I take this DMARD?

When should I call my healthcare provider?

Call your provider if you have:

• Fever.
• Rash.
• Nausea or vomiting.
• Symptoms of infection (sore throat, chills, fever).

Call your provider if you develop any side effect that bothers or worries you. Also, call if you are considering becoming pregnant or if you are pregnant.

A note from Cleveland Clinic

DMARDs are a class of drugs that treat rheumatoid arthritis and many other autoimmune disorders. You and your healthcare provider will review all the medication options and make the best choice for you. Each medication is unique with distinct side effects that need to be carefully checked. Your provider may adjust your dose, change DMARD or add other DMARDs to your treatment. Ask your provider about all the side effects of the particular medication you’ll be taking and what to watch for as you begin treatment with a DMARD.