Some drugs for the management of arthritis focus on merely treating symptoms, temporarily reducing the pain and inflammation of RA. But others, called disease-modifying anti-rheumatic drugs, or DMARDs, are able to change or slow the progression of the disease, helping to prevent severe joint damage and other complications from developing. (1)
Medication for rheumatoid arthritis typically falls into one of three categories:
The medications your doctor prescribes will usually change over the course of time. If following the treat-to-target paradigm, your doctor will continually monitor your disease activity (with serial examinations and lab work) and adjust your medications to help you reach your disease target — which in most cases is remission or low-disease activity.
Be sure to start a conversation with your doctor about a treat-to-target approach for RA. While treat-to-target yields superior outcomes versus standard RA care, it has not yet been widely adopted, according to a 2019 study. (3)
The Importance of Early Drug Treatment for Rheumatoid Arthritis
Rheumatoid arthritis may begin in a gradual and subtle way, but it ultimately causes joint damage in 85 percent of people with the disease. (4)
Given that the majority of this irreversible damage occurs within the first two years of the disease,?early diagnosis and treatment are vital?to protecting the joints and preventing disability. (1,2,4)
Treatment with disease-modifying drugs can help stop disease activity, as well as joint and bone destruction. Along with medication, various lifestyle changes can help reduce RA-related joint damage or reduce the risk of complications associated with RA (such as cardiovascular disease). These lifestyle changes include:
DMARDs for Treating Rheumatoid Arthritis
There is no cure for RA, but DMARDs are the gold standard of RA treatment because they can help both alleviate symptoms and prevent joint damage.
Each conventional (nonbiologic) DMARD is different, but they all work by slowing the inflammatory process of the body, protecting the joints from further damage. These drugs are generally prescribed at the time of or shortly after diagnosis. (5)
Which DMARD your doctor prescribes depends on numerous things, including your past history and other medical conditions, the severity of the disease, and the balance between possible side effects and the benefits of the DMARD. But for many with RA, one DMARD may not be enough to adequately control the disease, in which case your doctor may prescribe multiple medications to treat this form of arthritis.One concern with the use of most DMARDs is the increased risk of infection, so you should make sure you discuss this at length with your doctor.
Methotrexate Is a Popular DMARD Used to Treat RA
The most frequently used DMARD for RA is?methotrexate (Trexall), which takes up to six weeks to start working, with the full effect not seen until after 12 weeks of treatment. Up to 90 percent of people with RA take methotrexate at some point during treatment.
About 20 percent of patients eventually stop taking methotrexate due to its side effects, which include upset stomach, sore mouth, fatigue, and hair thinning due to a drop in folic acid levels from the drug. Patients are often given?folic acid supplements?to minimize these side effects.
Your doctor may prescribe other DMARDs along with methotrexate, including:
Biologic DMARDs for Treating Rheumatoid Arthritis
Biologic DMARDs work more quickly than conventional DMARDs — some in as little as two weeks — but must be injected. Many patients learn to inject the medication themselves at home without much trouble. The drugs can also be administered subcutaneously (under the skin) or intravenously in a clinic or hospital. These drugs interfere with the immune system’s ability to launch the damaging inflammatory process by targeting specific steps in this process.
What Is Anti-TNF Therapy?
The first types of biologics that hit the market work by binding and inhibiting tumor necrosis factor alpha (TNF), a pro-inflammatory protein. These drugs may be used in combination with methotrexate, though two biologics are never used in combination with each other. (8)
TNF inhibitors include:
- etanercept (Enbrel)
- infliximab (Remicade)
- adalimumab (Humira)
- certolizumab (Cimzia)
- golimumab (Simponi)?(7)
The Food and Drug Administration (FDA) warns that TNF inhibitors may be associated with an increased risk of lymphomas (cancer of the lymph nodes). But research from 2017 suggested these drugs don’t affect lymphoma risk, which may actually be due to RA-related inflammation.?(9)?This family of medications may increase the risk of certain skin cancers, however, so be sure to talk with your rheumatologist if you have been diagnosed with cancer.
Other biologics target other immune system factors, such as interleukin-1 (IL-1), IL-6, CD20-positive B cells, and T cell activity. These drugs are usually only prescribed if you’re unresponsive?or develop an adverse reaction to treatments with methotrexate and a TNF inhibitor. (1,2,4)
These other biologics include:
JAK Inhibitors for Difficult-to-Treat RA
A drug called?tofacitinib (Xeljanz)?is also available. It belongs to a new subclass of DMARDs called?JAK inhibitors, which work by blocking another part of the body’s immune system response:?Janus kinase (JAK) pathways. This type of DMARD, like conventional DMARDs, can be taken orally. (10)
A study from 2019 found that tofacitinib remained effective for at least eight years and safe for at least nine-and-a-half years. (11)
Two additional JAK inhibitors were approved by the FDA in 2018 and 2019: baricitinib (Olumiant), which is typically used alongside conventional DMARDs for people who have shown poor responses to certain biologics; and upadacitinib (Rinvoq), for adults with moderate to severe RA that is not being well-controlled by methotrexate.But then in 2021, the FDA issued a black box warning about JAK inhibitors (including tofacitinib, baricitinib, and upadacitinib), which concluded “there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” for patients who take these drugs when compared to those who took TNF inhibitors.
Corticosteroids for Treating Rheumatoid Arthritis
These drugs are often used for rapid control of worsening RA symptoms while waiting for DMARDs to take effect. They can quickly reduce pain, stiffness, swelling, and tenderness of joints.
But corticosteroids are only used for short-term relief because they can cause a number of serious side effects in the long run, including:
NSAIDs for Treating Rheumatoid Arthritis
NSAIDs are used for temporary RA relief because they are able to help with pain and minor inflammation, but they cannot reduce the long-term damaging effects of RA or change the course of the disease. (12,13)
Over time, NSAIDs can increase your risk of gastrointestinal bleeding, fluid retention, and heart disease.
Over-the-counter NSAIDs include:
Prescription NSAIDs include:
- diclofenac (Voltaren)
- piroxicam (Feldene)
- indomethacin (Indocin)
- meloxicam (Mobic)
- celecoxib (Celebrex)
- etodolac (Lodine) (5)
Controlling RA Symptom Flare-Ups With Medication
Even with regular treatment, you may occasionally experience?flare-ups?— periods of increased disease activity that cause spikes in symptoms.
Mild flare-ups can sometimes be treated at home with NSAIDs, rest, hot or cold compresses, or gentle exercise. If these treatments don’t work, your doctor may prescribe oral corticosteroids, which will help reduce the inflammation causing your symptoms, and possibly adjust the dose of any conventional or biologic DMARDs you may be taking.
Importantly, it’s best to try to treat your flare-up rather than take the wait-and-see approach to prevent further joint damage. (14)
Rheumatoid Arthritis Medications and Pregnancy
Research presented in September 2017 showed that as many as?half of women with RA stop taking their medication during pregnancy. But doing so can cause disease activity to increase, potentially impacting unborn babies. (15)
While some RA medications can be taken safely during pregnancy, others have been shown to cause harm to a developing baby. Be sure to talk with your rheumatologist at least six to nine months before trying to conceive so that appropriate changes (if needed) can be made to your RA therapy.
Editorial Sources and Fact-Checking
- Combe B, Landewe R, Daien CI, et al. 2016 Update of the EULAR Recommendations for the Management of Early Arthritis. Annals of the Rheumatic Diseases. 2017.
- Patient Education: Rheumatoid Arthritis Treatment (Beyond the Basics). UpToDate. June 30, 2022.
- Van Vollenhoven R. Treat-to-Target in Rheumatoid Arthritis — Are We There Yet? Nature Reviews Rheumatology. March 2019.
- Rheumatoid Arthritis. Johns Hopkins Arthritis Center.
- Rheumatoid Arthritis Treatment. Johns Hopkins Arthritis Center.
- Deleted, October 14, 2022.
- Donahue KE, Gartlehner G, Schulman ER, et al. Drug Therapy for Early Rheumatoid Arthritis: A Systematic Review Update. Comparative Effectiveness Review, No. 211. July 2018.
- Biologics. Arthritis Foundation. September 3, 2022.
- Mercer LK, Regierer AC, Mariette X, et al. Spectrum of Lymphomas Across Different Drug Treatment Groups in Rheumatoid Arthritis: A European Registries Collaborative Project. Annals of the Rheumatic Diseases. 2017.
- Kawalec P, Mikrut A, Wisniewska N, Pilc A. The Effectiveness of Tofacitinib, a Novel Janus Kinase Inhibitor, in the Treatment of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Clinical Rheumatology. July 23, 2013.
- Wollenhaupt J, Lee E-B, Curtis JR, Silverfield J, et al. Safety and Efficacy of Tofacitinib for up to 9.5?Years in the Treatment of Rheumatoid Arthritis: Final Results of a Global, Open-Label, Long-Term Extension Study. Arthritis Research & Therapy. April 5, 2019.
- Taming High Disease Activity in Early RA. Arthritis Foundation.
- NSAIDs. Arthritis Foundation.
- Markusse IM, Dirven L, Gerards AH, et al. Disease Flares in Rheumatoid Arthritis Are Associated With Joint Damage Progression and Disability: 10-Year Results From the BeSt Study. Arthritis Research & Therapy. August 31, 2015.
- Haroun T, Eudy AM, Jayasundara M, et al. Tough Choices: Understanding the Medication Decision-Making Process for Women With Inflammatory Arthritis During Pregnancy and Lactation. Arthritis & Rheumatology. September 18, 2017.
- FDA Requires Warnings About Increased Risk of Serious Heart-Related Events, Cancer, Blood Clots, and Death For JAK Inhibitors That Treat Certain Chronic Inflammatory Conditions. U.S. Food and Drug Administration. December 7, 2021.
- NAIMS Health Topics. National Institute of Arthritis and Musculoskeletal and Skin Diseases.
- Rheumatoid Arthritis: In Depth. National Center for Complementary and Integrative Health. January 2019.
- Understanding Methotrexate. Arthritis Foundation.