Rheumatoid arthritis (RA) is an autoimmune condition in which the immune system attacks the lining of the joints. Traditional and biologic disease-modifying antirheumatic drugs (DMARDs) are two forms of treatment.

Scientists developed many traditional DMARDs to treat other conditions, such as cancer.

More recently, scientists developed biologic DMARDs after gaining insight into the functions of specific molecules in a healthy immune system. These drugs mimic some of these molecules.

Below, we describe how the two types of treatment work, how they differ, and what side effects they can cause.

Traditional DMARDs can help control the signs and symptoms of RA. In some people with the condition, they limit joint damage, bone erosion, and progression to severe joint deformities.

If a person takes these medications, they may need less of another type of RA treatment: corticosteroids.

In recent years, researchers have learned more about the roles that specific molecules play in immune function, inflammation, and autoimmunity.

This understanding has helped researchers develop drugs that mimic molecules involved in healthy immune function. Among these drugs are biologic DMARDs.

Compared with traditional DMARDs, biologics are more targeted and effective at treating RA.

The side effect profiles of traditional DMARDs and biologics differ, though the two types of medication can sometimes cause the same adverse effects.

Also, the administration of these treatments is different. A traditional DMARD is usually a pill, taken orally. Biologics are made up of proteins and are delivered by intravenous infusion or injection.

Doctors use an ever-growing number of traditional DMARDs and biologics to treat RA.

Another group of medications, known as janus kinase (JAK) inhibitors, can also treat the condition. JAK inhibitors are oral small molecules that block immune cell signaling pathways.

Traditional DMARDs

Traditional DMARDs for RA include:

  • hydroxychloroquine (Plaquenil, Quineprox)
  • sulfasalazine (Azulfidine, Sulazine)
  • methotrexate (Otrexup, Rasuvo, Rheumatrex dose pack, Trexall)
  • leflunomide (Arava)
  • azathioprine (Azasan, Imuran)

Historically, doctors used other traditional DMARDs to treat RA — gold sodium thiomalate, penicillamine, and a device known as a Prosorba column — but they rarely use these today.

Although doctors do not consider the corticosteroid prednisone to be a classic DMARD, some studies suggest that it has disease-modifying properties. However, doctors use it minimally, due to the risk of side effects.

Biologic DMARDs

Biologic DMARDs for RA include:

  • Tumor necrosis factor (TNF) inhibitors: adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade)
  • Interleukin-1 inhibitor: anakinra (Kineret)
  • Interleukin-6 inhibitors: tocilizumab (Actemra), sarilumab (Kevzara)
  • T cell inhibitor: abatacept (Orencia)
  • B cell inhibitor: rituximab (Rituxan)

Several biosimilars are also on the market, and more are coming. Biosimilars are very similar to the original, branded biologics.

JAK inhibitors

JAK inhibitors for RA include:

  • tofacitinib (Xeljanz)
  • baricitinib (Olumiant)
  • upadacitinib (Rinvoq)

Experts have developed guidelines for treating RA, based on how effective and safe different treatments are. These guidelines evolve over time.

To treat mild RA, doctors typically prescribe a traditional DMARD, such as hydroxychloroquine or sulfasalazine.

To treat moderate to severe RA, doctors usually begin by prescribing methotrexate.

If the person’s symptoms do not adequately respond to this treatment, the doctor may add another medication to their treatment plan. For example, they may prescribe a TNF inhibitor.

If the person’s symptoms still do not respond sufficiently, the doctor will usually prescribe another medication with a different mechanism of action. They may also prescribe another medication if the person develops intolerable side effects.

Other factors may also affect the choice of medication, including:

  • whether the person has a history of tuberculosis (TB) infection, a positive screening for TB, or hepatitis B or C infection
  • the person’s history and risk factors for cardiovascular disease
  • the person’s kidney and liver function
  • the cost of treatment

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.

Also, researchers have associated TNF inhibitors with an increased risk of TB reactivation and hepatitis B reactivation in people with a history of these infections.

In addition, biologics can change the balance of immune processes. So sometimes, another autoimmune condition develops in people who take these medications.

For example, someone with RA who takes TNF inhibitors might develop psoriasis. Lupus, demyelinating conditions, and progressive multifocal leukoencephalopathy have also developed in people who were taking certain biologics.

Compared to biologics, traditional DMARDs are generally more likely to cause low white blood cell and platelet counts (cytopenia) and liver abnormalities.

JAK inhibitors are linked to an increased risk of blood clotting (thrombosis).

Doctors monitor people for side effects, based on their current medications and any other ongoing health conditions.

This monitoring usually entails blood tests for:

  • complete blood count
  • liver function
  • kidney function
  • lipid levels

Before prescribing many medications, a doctor asks about the person’s vaccine status and makes sure that they have the appropriate vaccinations.

A doctor also tests the person for infections such as TB, hepatitis B, and hepatitis C.

Without the right treatment, RA can cause:

  • joint damage
  • decreased quality of life, due to pain and inflammation
  • effects outside the joints, such as lung disease, inflammation of blood vessels, and a skin condition known as nodulosis
  • increased risk of cardiovascular disease, lung disease, and cancer

In addition to treating RA, it is important to manage any other ongoing health issues.

For example, diagnosing and treating diabetes, obesity, hypertension, and elevated lipid levels is important for decreasing inflammation and the damaging effects that these conditions can have.

Optimal dental care is also important. Periodontal disease may be a trigger for chronic inflammation and RA.

To help control symptoms of RA, I encourage people to:

  • Cease smoking. Smoking can trigger and exacerbate RA.
  • Eat a well-balanced diet. Eating a nutrient-rich diet that is high in anti-inflammatory foods is important for lowering inflammation and maintaining optimal nutrition.
  • Identify and limit food triggers. Learning whether certain foods contribute to inflammation is also important. Minimizing sugar intake may help, as may a diet that reduces or eliminates wheat and gluten.
  • Get regular exercise. It is key for each person to find an activity that works for them, such as tai chi, yoga, swimming, or walking.
  • Manage stress. Meditation, hobbies, and social activities can help with stress management.
  • Optimize sleep. Getting enough high-quality sleep every night is important.

Acupuncture may also help control symptoms of RA.

Scientists are continuing to explore the roles that different immune cells and molecules play in the development and treatment of RA.

Further understanding the role of JAK inhibitors is one focus of research, and scientists are currently developing a number of additional JAK inhibitors.

Vagal nerve stimulation is another area to watch for new developments.

Eventually, early diagnosis, targeted intervention, induction of remission, and reduced need for chronic maintenance therapy may move us forward to a “cure.”

In the meantime, a number of very effective therapies for for RA are available.


Nancy Carteron, M.D., is a San Francisco-area rheumatologist with a long-standing interest in autoimmune disease. She received her medical degree from Johns Hopkins University, with postgraduate training from Johns Hopkins University, Duke University, Stanford University, and the University of California, San Francisco. Early in her career, she gained extensive experience in molecular biology-virology and cellular immunology. During almost 30 years in clinical practice, she continued to serve as a consultant for therapeutic development, served as a principal investigator in clinical trials leading to the first approved biologic for RA, authored a key article on early biologics for RA, developed the Rheumatoid Arthritis in Pregnancy module for the American College of Physicians, and chaired a patient assistance foundation for RA. She continues her clinical work as a faculty member of the University of California, San Francisco and Berkeley.