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Drug Treatments for Rheumatoid Arthritis: What Are Your Options?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on March 4, 2021.

What is Rheumatoid Arthritis (RA)?

One of over 100 different arthritis types, rheumatoid arthritis (RA) is common and affects over 1.3 million people in the U.S. It is two to three times more common in women than in men, and is typically diagnosed between the ages of 30 and 60 years. It can affect the ability to work and one's quality of life dramatically.

So what is RA? Rheumatoid arthritis is an inflammatory disease of the joints in areas like the hands, feet or wrist. The joints become painful, stiff, and tender and may feel warm or look red.

Normally, inflammation is a beneficial process used for repair of injury or illness. However, in an autoimmune disease like RA, healthy tissues are attacked. RA cannot be cured but there are treatments that help control the pain, inflammation and joint destruction.

RA differs from osteoarthritis, which is due to the wear-and tear on the joints and cartilage over time.

What is the Goal of RA Treatment?

Minimizing pain, inflammation and joint damage are the top goals of rheumatoid arthritis (RA) treatment. Drug treatment that can slow down or even stop joint destruction are recommended for most patients.

Treatment should allow you to keep up with your normal daily activities and maintain a good quality of life with the fewest possible drug side effects.

You and your doctor will develop a long-term plan for your RA therapy. Becoming involved in your therapy is important for its success.

What Non-Drug Measures Are Used to Control RA?

Non-drug treatments are also a cornerstone of rheumatoid arthritis (RA) treatment, and should include:

  • joint rest and exercise
  • physical and occupational therapy
  • nutritional education
  • diet counseling

as important components of successful RA treatment.

You can learn to better control your RA symptoms and maximize your ability to stay active with work, physical fitness and social activities by combining non-drug therapies with your medicines.

In severe cases, joint replacement surgery may be elected to treat RA.

What is the First Line of Drug Treatment for RA?

Your rheumatoid arthritis (RA) drug treatment will be uniquely tailored to your needs. Your doctor will discuss the risks and benefits of drug treatment with you. Treatment will depend upon the severity and length of time you have had RA.

Your doctor may start treatment by prescribing one or more disease-modifying anti-rheumatic drugs (DMARDs).

A drug from the nonsteroidal or glucocorticoid anti-inflammatory drug class might be used initially or for more severe RA symptoms to control your acute pain and inflammation.

What are DMARDs?

Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) are the anchor drugs used for treatment of rheumatoid arthritis (RA), but their full effect may take one to three months. DMARDs:

  • decrease inflammation
  • lessen joint damage
  • help to maintain joint function.

Methotrexate (MTX) is a first-line DMARD that is often used in conjunction with an anti-inflammatory drug, such as ibuprofen (Motrin, Advil) or naproxen (Aleve).

Methotrexate is usually taken once per week as a pill or as an injection.

Other oral non-biologic DMARDs include hydroxychloroquine, leflunomide, and sulfasalazine.

What Are Common Side Effects with Methotrexate?

Methotrexate (MTX) side effects may include stomach upset, blurred vision, headache, mouth or lip sores, feeling tired, diarrhea and abnormal liver tests. MTX can reduce the production of certain blood cells and this may increase the risk for bleeding or bruising. There may be a greater risk for fevers and infections, too.

Regular blood tests may be ordered, and folic acid or leucovorin may be used to lessen the risk of some side effects. MTX and leflunomide should not be used in pregnancy or breastfeeding. Any woman with rheumatoid arthritis planning a pregnancy should consult with her doctor first.

What If a conventional DMARD is not fully effective?

Other treatments are available that can be added to non-biologic DMARD therapy for patients who do not respond or who have severe rheumatoid arthritis (RA) disease at diagnosis. Another DMARD might be added to treatment, or a biologic DMARD can be tried alone.

Biologic DMARDSs are also called targeted biologic agents or simply biologics.

Biologic DMARD examples include:

Biosimilars Available for Rheumatoid Arthritis

Many biosimilars are now available for RA, as well. A biosimilar is a product that is similar to a reference drug (the original one approved) and for which there are no clinically meaningful differences in terms of safety, purity, and potency. For example, Cyltezo is a biosimilar to Humira (Humira was the first adalimumab approved by the FDA).

Biosimilars may be more affordable, but must be specifically prescribed by your doctor. It's best to check with your insurance, as a specialty pharmacy may need to help coordinate your prescription.

Most biologics or biosimilars are given by injection and can be added to non-biologic DMARDs, NSAIDs or corticosteriods.

How Do Biologics Work in RA?

Biologics target proteins and other molecules in the immune system that cause inflammation, pain and joint destruction. The use of TNF blockers, with or without methotrexate, is recommended for patients with early rheumatoid arthritis who have more severe disease or who fail non-biologic DMARDs.

Common Tumor Necrosis Factor (TNF) blockers:

Select Non-TNF biologics:

Non-TNF biologics target other immune system molecules; they may be used if a TNF blocker plus methotrexate is not adequate. Do not use non-TNF biologics in combination with TNF blocking agents or other powerful immunosuppressants due to the possibility of an increased risk of infection.

What Special Precautions are Needed for TNF Blockers?

TNF blockers suppress the immune system and may increase the risk of getting an infection; report any signs or symptoms of an infection, such as a fever, to your doctor immediately. Also report any night sweats or weight loss that occurs during treatment.

You may need vaccinations prior to or during treatment with biologics. Tell your doctor if you have a history of congestive heart failure (CHF), cancer or hepatitis.

You will also be tested for tuberculosis (TB) before starting a biologic agent.

What Other Drugs Are Used in Combination with DMARDs and/or Biologics?

DMARDs, including the biologics are the backbone of rheumatoid arthritis (RA) treatment and help prevent pain and joint destruction.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are also used to alleviate pain and decrease inflammation but do not reduce joint damage.

Common NSAID examples include:

  • ibuprofen (Advil, Motrin)
  • naproxen (Aleve)
  • diclofenac
  • celecoxib (Celebrex).

Glucocorticoids (steroids) such as prednisone, prednisolone or triamcinolone can provide rapid relief and are given in pill form or by injection. However, these are usually given early in therapy to lower inflammation and pain while slower acting drugs like the DMARDs take effect. Glucocorticoids are also reserved for more severe RA or for flare-ups because they can cause severe side effects with long-term use.

Xeljanz: An Oral RA Treatment

Xeljanz (tofacitinib) was originally approved in November of 2012 for treatment of patients with moderate-to-severe RA who have had an inadequate response to methotrexate. The extended-release Xeljanz XR was approved in February 2016.

Xeljanz is not considered a biologic, but a small molecule agent that is made with traditional drug manufacturing processes.

Learn more: What is Xeljanz used for and is it a biologic?

Xeljanz was the first oral agent in a new class of drugs called Janus Kinase (JAK) inhibitors.

  • Xeljanz is given twice daily in pill form if you have had an inadequate response to methotrexate; the XR form is given once daily.
  • It can be used alone or with nonbiologic DMARDs such as methotrexate.

Like biologics, Xeljanz may be associated with serious side effects such as infections, cancer, and stomach or intestinal tears. Discuss the benefits and risks of this therapy with your doctor.

Kevzara Approved: May 2017

In May, 2017 the FDA approved a new IL-6 antagonist to treat rheumatoid arthritis -- Kevzara (sarilumab) -- from Regeneron and Sanofi. By blocking IL-6, an inflammatory cytokine, the swelling and pain linked to rheumatoid arthritis can be improved.

Kevzara is specifically used for the treatment of patients with moderate-to-severe rheumatoid arthritis who have had an inadequate response or cannot tolerate one or more disease-modifying antirheumatic drugs (DMARDs). It can be used alone or in combination with methotrexate (MTX) or other conventional DMARDs.

In studies, the most common side effects linked with Kevzara included:

  • neutropenia
  • increased liver enzymes
  • injection site redness
  • upper respiratory infections
  • urinary tract infections.

In the MOBILITY study, treatment with Kevzara plus MTX reduced signs and symptoms, improved physical function, and demonstrated significantly less radiographic progression of structural damage, compared to placebo plus MTX.

Olumiant for Adults with Moderate-to-Severe Rheumatoid Arthritis

In June 2018, Eli Lilly and Incyte announced the approval of Olumiant (baricitinib), a once-daily oral medicine for adults with an inadequate response to tumor necrosis factor (TNF) inhibitors. Roughly two-thirds of rheumatoid arthritis (RA) patients will not reach remission with their first tumor necrosis factor (TNF) inhibitor therapy.

Like Xeljanz (tofacitinib), Olumiant is a Janus kinase (JAK) inhibitor. Olumiant may be used alone or in combination with methotrexate or other non-biologic DMARDs. However, Olumiant use is not recommended for use with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants such as azathioprine or cyclosporine due to an increased risk for infection.

In clinical studies, Olumiant had a significant response rate when results were compared to placebo at Week 12 (49% versus 27%, respectively). A Boxed Warning warns for the risk of serious infections, malignancies and thrombosis.

According to the manufacturer, Eli Lilly, the price of Olumiant will cost about 60% less than the leading TNF inhibitor.

Interestingly, the combination of baricitinib (Olumiant) and remdesivir received Emergency Use Authorization (EUA) from the FDA for the treatment of hospitalized patients with COVID-19 in Nov. 2020.

AbbVie’s Oral JAK Inhibitor Rinvoq OK'd for RA

In August of 2019 the FDA cleared AbbVie's Rinvoq (upadacitinib), a 15 mg, once-daily oral Janus Associated Kinase (JAK) inhibitor, for adults with moderate-to-severe rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate (MTX).

  • In the SELECT Phase 3 studies, roughly 4,400 patients were evaluated. Across all treatment arms in five SELECT studies, Rinvoq met all primary and ranked secondary endpoints.
  • In SELECT-COMPARE, 71% of MTX patients treated with Rinvoq 15 mg plus MTX achieved ACR20 (a composite measure that captures at least a 20% RA improvement) compared to 36% treated with placebo plus MTX at week 12.
  • Common side effects included upper respiratory tract infections (common cold, sinus infections), nausea, cough, and pyrexia (fever).

Finished: Drug Treatments for Rheumatoid Arthritis - What Are Your Options?

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  • Singh JA, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care and Research 2016;68:1-25. Accessed Feb 23, 2020.
  • Rheumatoid Arthritis. Accessed March 4, 2021.
  • Up To Date. Patient Information: Rheumatoid Arthritis symptoms and diagnosis (Beyond the Basics). Accessed March 4, 2021.
  • Pfizer. Xeljanz XR Prescribing Information. Revised Feb 2016. Accessed March 4, 2021.
  • Kevzara. Product Label. Regeneron. Accessed March 4, 2021.

Further information

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