Medications to Treat Rheumatoid Arthritis

Goals, Available Drugs, Effectiveness, and Side Effects

Rheumatoid arthritis (RA) is a chronic type of arthritis resulting in pain and swelling. RA is a symmetrical condition, meaning it affects the joints on both sides of the body—such as your hands and knees. The involvement of several joints on both sides is what distinguishes RA from other forms of arthritis. RA may also affect the skin, eyes, GI, lungs, heart, and other vital organs.

Most people with RA take medication to manage their disease. When trying to figure out what medications to prescribe for RA, your healthcare provider will consider several factors, including your age, how active your RA is, and if you have other medical conditions.

Determining what medications will work can be challenging and requires a trial-and-error approach. The approach aims to determine which medications best control inflammation, ease pain, and allow you to have the best possible quality of life.

Platelet-rich plasma injection of the knee
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Treating Rheumatoid Arthritis

Because of recent advances in drug therapies, the outlook for people with RA has improved dramatically and remission is very possible.

The American College of Rheumatology has published criteria for what specific factors apply to the definition of remission. These include suppression of inflammation and stopping or slowing down disease progression in order to minimize disability and joint damage and maximize quality of life.

The most important goal in RA treatment is to reduce a person’s joint pain and swelling, and to maintain and improve joint function. Long-term, your healthcare provider will want to slow or stop the disease process that would eventually cause joint damage easily seen on X-rays.

Slowing down the disease process means inflammation is controlled, pain is reduced, and the potential for joint and organ damage is significantly reduced.

One of the more recent methods healthcare providers use to treat RA and get patients to low disease activity or remission is called treat-to-target (T2T). Research from the past two decades has shown T2T is the most appropriate strategy to “achieve superior clinical outcomes.”

T2T is a medical approach with a goal in mind—either the absence of inflammatory disease symptoms or low disease activity. Once goals are set, the treatment method is determined. Disease activity is measured frequently—usually over a three-month period—through lab testing and physical examinations.

If targets are not met, medications and/or medication doses are adjusted. The process will continue until the desired goal has been achieved. 

Drug Therapies

Medications for managing RA fall into five categories: Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, disease-modifying anti-rheumatic drugs (DMARDs), biologics, and Janus kinase (JAK) inhibitors.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs, such as ibuprofen (under the brand names Advil and Motrin) and naproxen (brand name Aleve), are recommended to relieve pain and minor levels of inflammation.

Your healthcare provider can prescribe a stronger NSAID at a dose much higher than what is used for headaches or minor aches. It should be noted that NSAIDs do not reduce the long-term damaging effects that RA has on your joints.

NSAIDs are typically first-line treatments for the symptoms of RA and other inflammatory diseases. Clinical studies of NSAIDs show that when a person discontinues NSAID treatment, symptoms of RA typically return.

COX-2 inhibitors are prescription NSAIDs that are more specialized in the way they work on inflammation. They inhibit cyclooxygenase (COX) enzymes the body uses to create inflammatory and painful chemicals called prostaglandins. Comparisons of dosages for NSAIDs and COX-2 inhibitors show comparable effectiveness.

This type of NSAID is typically prescribed if you have a history of discomfort with NSAIDS or other risks for gastrointestinal (GI) complications, such as an increased risk of bleeding or other stomach issues.

Most NSAIDs are known for causing serious side effects. This includes GI bleeding, fluid retention, and an increased risk of heart disease. Your healthcare provider will consider all the risks to determine if they outweigh the benefits of recommending and prescribing an NSAID for treating RA symptoms.

Steroids

Steroids—called glucocorticoids or corticosteroids—have potent anti-inflammatory effects. Examples of steroid drugs for treating RA are prednisone, methylprednisolone, and prednisolone.

Steroids may be taken in pill form, topically in a lotion or cream, injected directly into a joint, or by intravenous (through a vein) drug infusion. Steroids can quickly improve RA symptoms, including pain and stiffness, and joint inflammation.

Oral steroids are often prescribed for patients with RA, though current guidelines recommend limiting their use as much as possible. These medications should be taken only for short periods. 

These drugs work in two ways. The first way is by stopping the production of pro-inflammatory cytokines involved in RA joint inflammation and the erosion of bones in RA. The second way corticosteroids work is by targeting and suppressing cyclooxygenase-2 (COX-2).

Your healthcare provider may prescribe steroids to treat RA flares—periods where RA symptoms are more active. Your practitioner will want you to keep taking all your other treatments while taking low-dose steroids for a short period.

Your healthcare provider may also prescribe a corticosteroid if RA is limiting your ability to function. This is done until slower-acting drugs take effect to prevent joint damage and slow down your overactive immune system, which is the main cause of RA.

Steroid Side Effects

Steroids are known for causing severe side effects. Side effects of corticosteroids include:

  • Weight gain
  • Worsening diabetes
  • New or worsening high blood pressure
  • Increased risk of cataracts
  • Bone loss, including increased risk of osteopenia and osteoporosis
  • Increased risk of infection
  • Changes in mood
  • Stomach irritation

Because of the increased risk for side effects, your healthcare provider will prescribe the lowest dose possible for the shortest period of time for treating RA symptoms. In addition, steroids should not be stopped suddenly. The dose has to be reduced gradually over time, especially if you have been taking them for a while.

Long-term steroid use can decrease the body's natural ability to produce cortisol, the body's main stress hormone. A sudden stop of steroids can lead to withdrawal symptoms.

Traditional DMARDs

Disease-modifying anti-rheumatic drugs (DMARDs) are used to decrease inflammation and slow down the progression of RA. That means a person living with RA will have fewer symptoms and experience less joint and tissue damage over time. These drugs, unfortunately, cannot reverse joint damage.

There are two main types of DMARDs—traditional DMARDs and biologics. Traditional DMARDs are available in many different forms for treating RA, including methotrexate and sulfasalazine. Methotrexate is the most common DMARD prescribed for RA.

DMARDs work because they interfere with critical pathways in the immune system that are responsible for causing inflammation. Traditional DMARDs are usually given in pill form, and methotrexate is usually given once a week. Methotrexate may also be given as a weekly injection.

DMARD Side Effects

Because DMARDs are powerful systemic drugs (affecting the entire body), they may cause harsh side effects.

Common side effects of DMARDs include:

  • Stomach upset, such as nausea, vomiting, or diarrhea
  • Liver problems, which are less common than stomach troubles. Your healthcare provider will check your blood regularly to make sure these drugs aren’t harming your liver.
  • Blood problems, including anemia (low red blood cell counts)
  • Increased risk of infection

Biologics

Biological response modifiers—or biologics for short—are made using biotechnology. This means biologics are genetically engineered to behave like natural proteins of the immune system. Your healthcare provider may prescribe a biologic when a traditional DMARD isn’t helping.

A biologic won’t cure your RA, but it can significantly reduce RA's effect on your life. These drugs are expensive but are well worth their cost. They are known for significantly improving RA symptoms, slowing down the disease’s progression, and improving physical function and quality of life.

Biologics cause fewer side effects than older DMARDs. Additionally, people who don’t respond well to older treatments may benefit from treatment with a biologic. In some cases, biologics are given as a solo therapy, but more commonly, they are given in combination with a traditional DMARD, usually methotrexate.

Most biologics are given by injection under the skin. Others are given directly as an intravenous (in a vein) infusion.

Biologic Side Effects

Even though biologics are known for having fewer side effects, they still pose the potential for risks because they suppress the immune system. Side effects of biologics may include:

  • Severe infections, especially lung infections
  • Liver damage
  • Nausea and stomach discomfort
  • Pain or swelling at the injection site
  • Reduced ability to make new blood cells

Early clinical studies of biologics also showed an increased incidence of certain cancers. Most likely the cancers are not related to the medication, but to the underlying RA, especially in those with more severe disease. Nevertheless, the possibility that a patient may develop a cancer, especially skin cancer, related to these medications cannot be completely excluded.

Janus Kinase (JAK) Inhibitors

JAK inhibitors are a type of medication that inhibits the activity and response of one or more of the Janus kinase family of enzymes—JAK1, JAK2, JAK3, and TYK2. JAK inhibitors interfere with the signaling pathways of these enzymes.

Currently three JAK inhibitors—Olumiant (baricitinib), Xeljanz (tofacitinib), and Rinvoq (upadacitinib)—have all been approved by the Food and Drug Administration (FDA) for treating RA. More are currently in clinical trials and could be available for treating RA in the next few years.

JAK inhibitors are available as a pill taken twice daily.

Other drugs, including biologics, work by blocking inflammatory proteins. JAK inhibitors, on the other hand, prevent inflammation by blocking the inflammatory processes from inside cells. Research shows the anti-inflammatory potential of JAK inhibitors is similar to—and in some cases higher than—that of biologics.

Much like traditional DMARDs and biologics, JAK inhibitors suppress the immune system, which means if you take these drugs, you are more vulnerable to serious infections.

Research also shows that Xeljanz, Olumiant, and Rinvoq may increase the risk of heart-related events, like heart attack or stroke, in addition to cancer, death, and blood clots. Patients with a history of diverticulitis may be at increased risk of bowel perforation as well.

JAK Inhibitor Side Effects

Other less serious side effects that eventually go away once your body has gotten used to the drug include:

  • Stomach discomfort, including diarrhea, bloating, and gas
  • Headache
  • Cold symptoms, including a sore throat and a stuffy or runny nose
  • Dizziness
  • Fatigue
  • Easy bruising

Any ongoing side effect or shortness of breath should be reported to your healthcare provider.

A Word From Verywell

Work with your healthcare provider to find the most effective RA medications for you and your unique situation. With all the options out there, you and your practitioner are likely to find something to ease RA symptoms and improve your function and overall quality of life.

It is also important to meet with your healthcare provider regularly so they can monitor side effects and make changes to your treatments as needed. Your practitioner will also order blood and other testing to determine if treatment is effective and monitor any side effects.

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