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Xeljanz vs. Humira for Rheumatoid Arthritis: 6 Things to Consider

Christina Aungst, PharmDJoshua Murdock, PharmD, BCBBS
Updated on January 26, 2024

Key takeaways:

  • Xeljanz (tofacitinib) and Humira (adalimumab) are both effective treatment options for rheumatoid arthritis (RA). Humira is an injectable biologic medication that’s injected once a week or every other week. Xeljanz is an oral medication that’s taken once or twice daily. 

  • Xeljanz and Humira are considered similarly effective at treating RA symptoms and preventing joint damage. But they’re typically only prescribed if methotrexate isn’t effective or well-tolerated.

  • Both medications can raise your risk of infection. But long-term safety studies have shown that Xeljanz may raise your risk of developing serious heart problems and cancer more than Humira. But these side effects are very rare.

  • There are ways to save on Xeljanz and Humira. If you’re eligible, manufacturer savings cards can help make your prescription more affordable. Humira also has a number of biosimilar options that can help you save on the cost of your medication.

Access savings on related medications

A man receives an injection in his abdomen.
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If you're living with rheumatoid arthritis (RA), you're part of a community of 1.5 million people in the U.S. facing this inflammatory condition. It’s typically diagnosed between the ages of 30 and 60 years old, and 3 out of every 4 people with RA are female. The hallmark symptoms of RA include pain and swelling in multiple joints — especially in the hands and feet — along with morning stiffness lasting over 30 minutes. 

While there isn't a cure for RA yet, medications play a key role in slowing down the progression of your condition and reducing joint pain. Options include older medications such as methotrexate and injectable options such as Humira (adalimumab). But newer oral medications, such as Xeljanz (tofacitinib), are also available. 

Wondering about the differences? Let's explore six of them together so you can make an informed decision about which medication might be the best fit for you.

1. Neither Xeljanz or Humira are considered first-choice treatment options for RA

Typically, RA treatment starts with a group of medications called disease-modifying antirheumatic drugs (DMARDs). DMARDs help reduce inflammation and prevent joint damage caused by RA.

Methotrexate is a traditional oral DMARD that’s considered a first-choice option for RA. If methotrexate or a similar medication doesn’t work well enough alone, your healthcare provider may add on a medication or change your prescription to a different medication altogether. The next step is usually a different type of DMARD — a biologic or other medication that targets a specific part of your immune system. That’s where Humira and Xeljanz come in. They’re most often prescribed when a first-choice RA treatment isn’t working or is causing problems for you.

2. Xeljanz and Humira work differently

While both Xeljanz and Humira target your immune system to treat RA, they don’t work in exactly the same way.

Humira belongs to a group of medications called biologics. More specifically, Humira is a type of biologic called a tumor necrosis factor (TNF) inhibitor. People with RA typically have very high levels of TNF in their joints, which is a protein involved in inflammation. By blocking the activity of TNF, these medications help lower the inflammation in your joints and prevent damage caused by RA.

Xeljanz is a Janus kinase (JAK) inhibitor. It blocks the actions of JAK proteins, which play a role in creating inflammation in our bodies. JAK is also overactive in people with RA, which leads or contributes to symptoms such as excess swelling and joint pain. So blocking it helps treat the symptoms and progression of RA in your body. Although it works in a similar way to Humira, Xeljanz isn’t a biologic.

3. Humira is an injection, while Xeljanz is an oral tablet

One of the major differences between Humira and Xeljanz is how you take them.

Humira and similar biologics are only available as injections. Humira comes in pre-filled syringes or auto-injector pens that you’ll inject under your skin once a week or every other week. 

Xeljanz and other JAK inhibitors are oral medications you can take by mouth. Xeljanz comes in an immediate-release (IR) tablet or oral solution that you’ll take twice a day. It also comes in an extended-release (XR) tablet that you’ll only take once daily.

Keep in mind: Needles may be intimidating for some people. But you’ll only need a Humira injection once a week at most. And you can give it to yourself at home once you’ve been trained to do it properly. So an injection may be more convenient for some people than remembering to take a pill every day.

4. Xeljanz and Humira are both effective RA treatment options

There are a number of studies comparing Xeljanz to biologic medications, including Humira. In most cases, the studies compare how well the medications work when they’re used in combination with methotrexate.

In 2012, a phase 3 clinical trial on Xeljanz showed that it worked better than placebo (a pill with no medication in it) and provided a similar amount of symptom relief as Humira. Both medications were taken along with methotrexate. The results of this study contributed to Xeljanz’s FDA approval for RA.

In 2017, a larger follow-up study was published comparing Xeljanz to Humira (both taken in combination with methotrexate). It found that people who took Xeljanz and methotrexate together experienced just as much symptom relief as those who received Humira with methotrexate. 

The same study also looked at people who took Xeljanz alone (without methotrexate). They did not do as well as the other two groups. But a similar study found that Xeljanz alone was similarly effective to either medication combined with methotrexate.

A review published in 2017 looked at all available research at the time comparing Xeljanz to biologics, including Humira. Overall, Xeljanz worked just as well as biologic medications. The review also noted that the number of people who stopped taking either medication due to side effects was similar.

A 2023 study followed about 850 people taking Xeljanz or Humira for RA. It showed both medications had similar effectiveness after 9 months of treatment.

Keep in mind: Clinical studies look at the overall effectiveness of a medication. But each individual responds to autoimmune treatments differently. What works for one person may not work well for another. Your provider will work with you to find the option that works best for your personal needs.

5. Xeljanz and Humira have different risks to consider

Xeljanz and Humira share similar side effects, such as an increased risk of infection while you’re taking them. But there are a few that set them apart.

Heart problems

In early 2021, Xeljanz’s manufacturer announced that people taking this medication may have a higher risk of dying from blood clots or heart-related problems than those treated with TNF inhibitors. Humira also has some risks when it comes to the heart. It can cause or worsen heart failure.

For both medications, these risks are higher if you already have heart problems. So be sure to speak with your provider about your existing medical conditions to help them choose the safest RA treatment for you.

Cancer risk

An increased risk of cancer is a rare but possible side effect of both Humira and Xeljanz. Xeljanz has a higher risk of lymphoma and lung cancer than TNF inhibitors. Humira can also raise your risk of cancer, particularly lymphoma, leukemia, and skin cancer. 

Thankfully, cancer is very rare with both of these medications. But if you have a personal or family history of any cancers, be sure to speak with your provider about the best ways to protect yourself while you’re taking these medications.

6. Humira has several more affordable biosimilars available. Xeljanz is only available as a brand-name medication

Xeljanz is only available as a brand-name medication. GoodRx can help you navigate between copay savings cards and patient assistance programs to save money on your prescription. If you have commercial insurance, you may be eligible to pay as little as $0 for a 30-day supply of Xeljanz using a savings card from the manufacturer. If you’re uninsured or underinsured, a patient assistance program is also available.

Humira is also available as a reference (“brand-name”) medication. You can pay as little as $5 per month for Humira with a copay card from the manufacturer if you have commercial insurance. A patient assistance program is also available.

Because they’re made using living sources, biologic medications don’t have generic versions in the traditional sense. Instead, they have biosimilars — medications that have a highly similar structure and function as their original (reference) biologic. And they’re often available at a lower cost. Humira biosimilars include:

  • Abrilada

  • Cyltezo

  • Amjevita

  • Hadlima

  • Hulio

  • Hyrimoz

  • Idacio

  • Yuflyma

  • Yusimry

All Humira biosimilars currently have copay cards available that help you pay as little as $0 per treatment if you have commercial insurance. A patient assistance program is also available for some biosimilars. Your healthcare provider can help determine which form of Humira is best for you based on your needs and insurance coverage.

The bottom line

Xeljanz (tofacitinib) and Humira (adalimumab) are similarly effective medications for treating rheumatoid arthritis (RA). In most cases, you’ll take methotrexate or a similar medication first before trying Xeljanz or Humira. Humira is a type of biologic medication known as a tissue necrosis factor (TNF) inhibitor. Xeljanz isn’t a biologic — it belongs to a class of medications called Janus kinase (JAK) inhibitors. Xeljanz is an oral tablet you’ll take once or twice a day, while Humira is an injection under the skin once a week or every other week.

Both medications can raise your risk of infection while you’re taking them. But Xeljanz can raise your risk of fatal heart problems and certain types of cancer more than Humira does. While these effects can sound scary, keep in mind they very rarely happen. Your healthcare provider can help you choose the best RA treatment option based on your medical history, insurance coverage, and personal preferences.

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Why trust our experts?

Christina Aungst, PharmD
Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.
Stacia Woodcock, PharmD
Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.
Joshua Murdock, PharmD, BCBBS
Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

References

A-S Medication Solutions. (2023). Humira - adalimumab [package insert]

Arthritis Foundation. (2021). Rheumatoid arthritis: Causes, symptoms, treatments and more

View All References (11)

Bergrath, E., et al. (2017). Tofacitinib versus biologic treatments in moderate-to-severe rheumatoid arthritis patients who have had an inadequate response to nonbiologic DMARDs: Systematic literature review and network meta-analysis. International Journal of Rheumatology

Deakin, C. T., et al. (2023). Comparative effectiveness of adalimumab vs tofacitinib in patients with rheumatoid arthritis in Australia. Journal of the American Medical Association Network Open

Ellis, C. R., et al. (2023). Adalimumab. StatPearls

Fleischmann, R., et al. (2017). Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): A phase 3b/4, double-blind, head-to-head, randomised controlled trial. The Lancet

Fraenkel, L., et al. (2021). 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. American College of Rheumatology. 

Malemud, C. J. (2018). The role of the JAK/STAT signal pathway in rheumatoid arthritis. Therapeutic Advances in Musculoskeletal Disease. 

Pfizer. (2021). Pfizer shares co-primary endpoint results from post-marketing required safety study of Xeljanz (tofacitinib) in subjects with rheumatoid arthritis (RA)

Reed, G. W., et al. (2019). Real-world comparative effectiveness of tofacitinib and tumor necrosis factor inhibitors as monotherapy and combination therapy for treatment of rheumatoid arthritis. Rheumatology and Therapy

U.S. Food and Drug Administration. (2022). FDA approves boxed warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR)

Van Vollenhoven, R. F., et al. (2012). Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. The New England Journal of Medicine

Vasanthi, P., et al. (2007). Role of tumor necrosis factor-alpha in rheumatoid arthritis: A review. Journal of Rheumatology.

GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines.

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