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When your joints ache, you may chalk it up to an old injury or to osteoarthritis — the wearing away of cartilage that’s common in older age. But for two million people in the United States, aching joints are caused by rheumatoid arthritis (RA) — when the immune system mistakenly attacks the tissues lining the joints.

“People commonly assume RA pain is due to aging, overuse, or even the flu,” says Robert Shmerling, M.D., a rheumatologist at Harvard-affiliated Beth Israel Deaconess Medical Center, and medical editor of the Harvard Special Health Report Rheumatoid Arthritis.

Symptoms and diagnosis

Unlike osteoarthritis, which is limited to the joints and can often be treated with mild pain relievers or exercise or resolved with joint replacement, RA is a progressive disease that can affect the whole body, including the heart, lungs, and eyes. It may damage the joints, tendons, and bones. “The biggest tip-off to RA is the presence of persistent swelling in multiple joints,” says Shmerling. “That does not occur with most other causes of joint pain.” Other classic RA symptoms include joint pain that is worse in the morning or better with movement, and persistent fatigue.

Diagnosis typically involves symptom assessment, physical examination findings, blood test results, as well as x-rays. “In confusing cases, ultrasound or MRI can be helpful,” says Shmerling.


Shmerling says it’s important to begin treating RA as soon as possible, because medication may help slow the disease process. “Delaying treatment will, on average, lead to more joint damage and loss of joint function,” he explains. In most cases, the first-line treatment is methotrexate (Rheumatrex, Trexall).

Medications do not reverse damage or improve dexterity, strength, balance, or stamina. They also do not address other aspects of health — such as depression, pain, or the impact of excess weight.

Other therapies include exercise, splinting, weight loss and smoking cessation. The role of heat or cold therapy and other alternative treatments is uncertain. “As long as these other treatments seem safe to me, I encourage patients to explore what works for them,” says Shmerling.

Drug treatment may prevent RA from progressing and causing more damage to the body. Most RA drugs fall into one of three classes:

Nonbiologic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (Rheumatrex, Trexall), have a broad effect on immune system function, which can help slow the disease process and protect the joints from damage. They also help relieve symptoms. These are generally offered as soon as the RA diagnosis is established, but they may take up to 12 weeks to work. Side effects vary from one drug to another and range from fatigue to liver problems. Screening and monitoring can prevent many side effects.

Biologic DMARDs, such as etanercept (Enbrel) and infliximab (Remicade), help relieve symptoms and prevent joint damage. They have a more targeted effect on immune system function than nonbiologic DMARDs, and are considered the most effective drugs for RA. However, they are expensive and can be given only by injection. They are usually reserved for people who do not improve enough with methotrexate or other medications. Because these drugs suppress parts of the immune system, people who take them are at increased risk for infections, especially tuberculosis.

Janus kinase inhibitors, such as tofacitinib (Xeljanz), help relieve symptoms and prevent joint damage by interrupting inflammatory signals as they enter cells. Possible side effects include shingles, allergic reactions, diarrhea, headache, runny or stuffy nose, and sore throat. An advantage of these drugs, in comparison to biologic DMARDs, is that they are pills, not shots or medicines infused into your veins.

Both Janus kinase inhibitors and biologic DMARDs have price tags of about $20,000 or more per year. Insurance plans often pay only some of the costs.

Until the above medications take effect, doctors may recommend low doses of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin), or corticosteroids, such as prednisone. But these medications do not protect the joints from damage, and long-term use is linked to dangerous side effects.

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