Rheumatoid Arthritis: Treatment Advances Reduce Pain, Slow Progression

While joint pain and swelling are common symptoms of more than 100 different forms of arthritis, rheumatoid arthritis (RA) can damage more than a person’s joints.

Rheumatoid arthritis, an autoimmune disease that is second only to the degenerative “wear-and-tear” disease of osteoarthritis, affects about 1.5 million people in the United States. When left untreated, rheumatoid arthritis can lead not only to chronic pain, but also disability and organ damage. Plus, it can increase the risk of cardiovascular disease.

"We think of rheumatoid arthritis as a condition that primarily affects the joints, but it can affect virtually any organ, including a person’s skin, eyes, lungs, and heart," says Betty Hsiao, MD, a Yale Medicine rheumatologist. "Treatment is important so that people can maintain their mobility and their function by controlling inflammation—not only in their joints but also systemically so other organs are not affected."

Symptoms of this disease can be challenging to manage, but researchers have made progress in treating rheumatoid arthritis, Dr. Hsiao explains. There is currently no cure, but rheumatologists (physicians who treat musculoskeletal diseases and certain autoimmune conditions) now have medication options that can decrease or prevent the progression of disease.

For example, when a person is diagnosed with rheumatoid arthritis, a class of drugs called disease-modifying antirheumatic drugs (DMARDs), which suppress the body's immune system to prevent inflammation, has long been the standard recommendation to slow progression and reduce symptoms.

Now, newer FDA-approved DMARDs known as Janus kinase (JAK) inhibitors, which target specific proteins in the body that lead to inflammation, are oral medications that are highly effective in slowing the damage rheumatoid arthritis causes in the body.

Other approaches are also being recommended to help manage the disease. The American College of Rheumatology created its first set of guidelines in 2022 for comprehensively managing rheumatoid arthritis with the addition of exercise, rehabilitation, and diet—alongside medication. The guidelines strongly encourage "consistent engagement in exercises," for example, and conditionally recommend other interventions, including physical therapy.

In healthy people, the immune system protects against illness by fighting off germs and other foreign substances that enter the body. But in those with rheumatoid arthritis, the immune system mistakenly attacks healthy joint tissue, causing inflammation that can damage bones and organs.

Unlike other forms of arthritis, rheumatoid arthritis usually affects the same joints on both sides of the body. Typically, the condition attacks smaller joints first, such as those in the hands and feet.

"If someone is developing signs and symptoms of painful and swollen joints—particularly with prolonged stiffness in the morning or after periods of inactivity—along with fatigue, perhaps fever and just not feeling well, that would prompt an evaluation," Dr. Hsiao says.

If you are showing such early symptoms of rheumatoid arthritis, discuss this with your primary care physician, who can refer you to a rheumatologist for an evaluation and possible treatment.

There is no single test to detect rheumatoid arthritis, so rheumatologists use a combination of a person’s symptoms and history along with physical examinations, blood work, X-rays, MRIs, and ultrasounds to make a diagnosis.

Blood work can reveal certain proteins that attack healthy tissue, including rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Blood tests might also show inflammatory markers, such as elevated sedimentation rate and higher levels of C-reactive protein. Your doctor will take all these results into account. Early diagnosis and treatment are critical to reduce symptoms.

Anyone can develop rheumatoid arthritis, but researchers have identified several factors that may increase the risk for the condition:

• Sex: Women are two to three times more likely to develop rheumatoid arthritis than men, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

• Genes: People with a first-degree relative (parent, sibling, or child) with rheumatoid arthritis are more likely to develop the disease.

• Smoking: Cigarette smoking can increase the risk of developing rheumatoid arthritis, particularly in people with certain genes.

• Age: People between ages 30 and 60 are more likely to develop the condition, but young-onset rheumatoid arthritis and elderly-onset rheumatoid arthritis can affect younger and older individuals.

• Obesity: Obesity is associated with a higher risk of developing rheumatoid arthritis and having a worse treatment outcome.

• Periodontitis: Researchers have identified gum disease as a possible risk factor for rheumatoid arthritis.

If you’re diagnosed with rheumatoid arthritis, most rheumatologists begin treatment with a DMARD. These medications have been used for decades to treat the disease.

"Normally, we start with the conventional ones first," Dr. Hsiao says. "Methotrexate is really our gold standard as a starting medication for rheumatoid arthritis given its long track record of efficacy and safety." It is taken once a week in oral or injectable forms and often used as a stand-alone therapy as well as in combination with other DMARDs.

However, because DMARDs are immunosuppressants, they may make some people more susceptible to other infections. Your rheumatologist may suggest pausing the use of a DMARD if you come down with another illness, such as the flu or a cold. Along with DMARDs, doctors may also prescribe corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and pain. Unlike DMARDs, NSAIDs do not slow down the progression of the disease.

If traditional DMARDs aren’t effective, your doctor may suggest switching to newer alternatives such as biologic DMARDs or targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs), including JAK inhibitors, which target more specific parts of the immune system. The most common side effects of biologic DMARDs and tsDMARDs are an increased risk of infections. Biologic DMARDs that are injected may carry a risk of injection-site reactions, and those administered intravenously may have a risk of infusion reactions. Typically, people who are on these medications need to have regular blood work to monitor for any abnormalities, such as liver problems or blood disorders.

"Sometimes, after initial options are tried and rendered ineffective for patients, it's not always clear which medications are the next best step, so that’s where shared decision-making is very important to elicit the patient's preferences as part of the treatment decision," explains Dr. Hsiao. Some people may prefer treatments that cost less, are easier to administer, or have fewer possible side effects, for example. "We also talk about other behavioral and lifestyle changes to optimize health," she says.

Maintaining a healthy lifestyle is also critical for reducing rheumatoid arthritis symptoms. The American College of Rheumatology recommends four major types of exercise to reduce pain and disability: flexibility exercises (such as ankle circles, knee extensions, and hip rotations); strengthening exercises (such as resistance band squats, biceps curls, and chest presses); aerobic exercises (such as walking and bicycling); and body awareness exercises (such as yoga and tai chi), which help the body sense its own movement and location in space.

"We rely on our colleagues in physical and occupational therapy to help our patients get acquainted with some of the exercises that they might need to do," Dr. Hsiao says.

Maintaining a healthy diet rich in whole foods, such as vegetables, fruits, whole grains, and nuts and seeds, and quitting smoking can also help improve the quality of life of people with rheumatoid arthritis.

"Psychosocial interventions and stress relief are also important,” Dr. Hsiao adds. “So is having a solid social support system and engaging with your friends and family. Managing stress is critical, because it can also play a role in autoimmune diseases."