DMARD Overview: The Essential Facts About These Diverse Anti-Inflammatory Medications

Would you believe that injecting gold could treat rheumatoid arthritis (RA)? Well, back in the 1930s, they did just that. A injection of gold — the first disease-modifying antirheumatic drug (DMARD) — was given to people with RA to help lower inflammation and reduce joint pain.

Fast forward to today, and many more proven DMARDs have been developed. They treat people living with inflammatory health conditions. People with conditions such as RA, psoriatic arthritis (PsA), systemic lupus erythematosus, and more all have several DMARDs to choose from. 

Here we’ll review what DMARDs are, how they work as anti-inflammatory treatments, and how to choose the best one for you.

What are DMARDs?

DMARDs are a class of medications that aim to lower pain and inflammation. They fall into two main categories: non-biologic DMARDs and biologic DMARDs.

• Non-biologic DMARDs: These include both conventional DMARDs and Janus kinase (JAK) inhibitors. Conventional DMARDs broadly affect the immune system, while Janus kinase (JAK) inhibitors work in a more targeted way.

• Biologic DMARDs: These are newer medications with a complex structure. They’re derived from natural and living sources, and they target specific pathways of the immune system.

How do DMARDs work?

DMARDs work by suppressing the body’s overactive immune system. This helps slow down inflammatory responses. By lowering inflammation, DMARDs can help relieve symptoms, prevent long-term damage, and slow the progression of autoimmune conditions such as RA, PsA, and Crohn’s disease.

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What is the difference between DMARDs and immunosuppressants?

There’s some overlap between the two.

Immunosuppressants are medications that weaken the immune system. Some immunosuppressants, such as cyclosporine (Sandimmune) and azathioprine (Imuran), were originally developed to prevent organ transplant rejection. But some immunosuppressants can now also be used to treat autoimmune conditions. 

Conventional DMARDs, biologic DMARDs, and JAK inhibitors are all considered immunosuppressants to some degree.

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Conventional DMARDs

Conventional DMARDs are typically recommended first. They’re safe and effective overall, and they also tend to be more affordable than biologic DMARDs and JAK inhibitors.

Conventional DMARDs each work differently. But their goal is to suppress the immune system. They work in a broader, more nonspecific way than biologic DMARDs and JAK inhibitors. Commonly recommended conventional DMARDs include:

• Methotrexate (Rheumatrex, Trexall)

• Sulfasalazine (Azulfidine)

• Hydroxychloroquine (Plaquenil)

• Leflunomide (Arava)

• Azathioprine (Imuran)

• Apremilast (Otezla)

• Cyclosporine (Neoral)

• Mycophenolate (CellCept)

• Cyclophosphamide (Cytoxan)

Conventional DMARDs are usually taken as a pill by mouth. And they can take weeks to start working. For example, methotrexate can take about 6 to 8 weeks to take effect. But everyone’s response to treatment is different, so it may take less or more time for you to notice the effects.

Biologic DMARDs

If your symptoms don’t improve while taking conventional DMARDs, the next step is usually to try a biologic DMARD. Biologic DMARDs target specific pathways of the immune system that contribute to the production of inflammation-causing proteins. They work in a more precise way than conventional DMARDs, and they typically start working more quickly.

Biologic DMARDs are categorized based on the part of the immune system they target.

Biologic DMARDs are typically given as an injection or infusion into the vein. Some are available as subcutaneous (under the skin) injections. Biologic DMARDs can start working in as little as 2 weeks, but some may need up to 6 months to take full effect.

Note: Many biologic DMARDs have biosimilars available, too. Think of biosimilars as generic versions of a biologic medication. They’re highly similar to the original product, but they're often available at a lower price. 

JAK inhibitors

JAK inhibitors are another set of non-biologic DMARDs. They’re a newer class of medications that work by blocking inflammatory JAK proteins.

JAK inhibitors are somewhat similar to biologic DMARDs in the ways that they work, but they’re conveniently taken as a pill by mouth. They’re not given as an injection into the vein or under the skin. So they’re a good choice if you don’t like needles. They’re also a good option if other DMARDs haven’t been effective for your symptoms.

Common JAK inhibitors for autoimmune conditions include:

• Tofacitinib (Xeljanz)

• Upadacitinib (Rinvoq)

• Baricitinib (Olumiant)

• Ruxolitinib (Opzelura)

• Abrocitinib (Cibinqo)

• Ritlecitinib (Litfulo)

JAK inhibitors can start working in as soon as 2 weeks, but they can take up to 3 months to take full effect. JAK inhibitors may not be a good choice for you if you have a history of blood clots, cancer, or heart problems. A very small number of people who took certain JAK inhibitors in clinical studies had a higher risk of experiencing these complications.

Notable DMARD side effects to keep in mind

Every DMARD has its own unique side effect profile. Make sure to defer to your medication’s labeling to learn what to expect. 

Still, there are some side effects that are common among the group. Common conventional DMARD side effects include nausea and diarrhea. Biologic DMARDs are more likely to cause headache, injection site reactions, and infusion reactions. JAK inhibitor side effects tend to include infections, acne, and nausea.

What’s more, all forms of DMARDs could raise your risk of developing a serious infection. Because of this risk, it's important to stay up to date on your immunizations. It's also a good idea to wash your hands regularly and avoid people who are sick as an added precaution.

Certain biologic DMARDs, such as TNF inhibitors, can also raise your risk of reactivating a tuberculosis (TB) infection if you have a history of TB. And in rare cases, TNF inhibitors have been linked to new cases of lymphoma and some skin cancers.

How to choose the best DMARD for you

One DMARD isn’t better than the rest. Everyone responds differently to medications — especially autoimmune treatments. Your healthcare professional can help you choose the best DMARD for you based on the severity of your symptoms, expected side effects of the treatment, and other health conditions you may have.

Logistics are another factor. You may prefer to take a daily pill instead of going to a clinic to receive an infusion, or vice versa. Cost and potential insurance coverage may also impact your choice, as biologic DMARDs and JAK inhibitors tend to be more costly.

You can discuss the risks and benefits of each type of DMARD and what to expect from treatment with your healthcare professional. Some DMARDs may work better for you than others and it may take time to find the one that works best for you.

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Written by:

Sonja Jacobsen, PharmD, BCPS, BCOP

Sonja Jacobsen, PharmD, BCPS, BCOP,  is a clinical oncology pharmacy specialist currently practicing in Seattle. She has been practicing as a pharmacist since 2015 and is licensed to practice in Washington state and North Carolina.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Tegan Smedley, PharmD, APh

Tegan Smedley, PharmD, APh, has 10 years of experience as a pharmacist. She has worked in a variety of settings, including retail, hospital, and ambulatory care.

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