Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.

Prescription Name and Overview

Xeljanz blocks the activity of certain enzymes in the body that affect immune system function.

Xeljanz is used to treat moderate to severe rheumatoid arthritis or active psoriatic arthritis (PsA) in adults who have tried methotrexate other medications without successful treatment of symptoms.

Xeljanz is sometimes given in combination with methotrexate or other arthritis medicines.

Xeljanz is also used to treat adults with moderate to severe ulcerative colitis.

Generic Name and Overview

Tofacitinib is an oral drug used for treating rheumatoid arthritis. It belongs to a class of drugs called Janus kinase (JAK) inhibitors. JAKs are enzymes (proteins) that regulate chemical signaling pathways that control biologic processes such as blood formation and the immune response that causes the pain, tenderness and swelling of inflammation. JAKs are found in many cells, especially stem cells in bones and joints. Inhibition of JAKs by tofacitinib prevents inflammation and tissue destruction that is associated with the inflammation of rheumatoid arthritis. Tofacitinib was approved in November 2012.

OTC  Name and Overview

Manufacturer

The manufacturer of Xeljanz is Pfizer, Inc.

Labeled Indications

Xeljanz is a Janus kinase (JAK) inhibitor. Its labeled indications are the following:

1. Rheumatoid Arthritis: Xeljanz is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs). Limitations of Use: Use of Xeljanz in combination with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
2. Psoriatic Arthritis: Xeljanz is indicated for the treatment of adult patients with active psoriatic arthritis who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs). Use of Xeljanz in combination with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
3. Ulcerative Colitis: Xeljanzis indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC). Limitations of Use: Use of XELJANZ in combination with biological therapies for UC or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Active Ingredients

The active ingredient in Xeljanz is tofactinib.

What Is It Used For?

How Does it Work?

Xeljanz works by inhibiting the JAK pathway — a signaling pathway inside cells that plays a significant role in inflammation associated with rheumatoid arthritis. JAKs are intracellular enzymes that transmit signals which arise from cytokine or growth factor-receptor interactions on the cell membrane.

What are the Approved Uses?

Xeljanz is taken orally, a 5 mg pill taken twice daily. It may be taken with or without food. An 11 mg once-daily dose is also now available as Xeljanz-XR (extended release).

Production Anecdotes / History

The potential significance of JAK3 inhibition was first discovered in the laboratory of John O’Shea, an immunologist at the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH). In 1994, Pfizer was approached by the NIH to form a public-private partnership in order to evaluate and bring to market experimental compounds based on this research. Pfizer initially declined the partnership but agreed in 1996, after the elimination of an NIH policy dictating that the market price of a product resulting from such a partnership would need to be commensurate with the investment of public taxpayer revenue and the “health and safety needs of the public.” Pfizer worked with O’Shea’s laboratory to define the structure and function of JAK3 and its receptors, and then handled the drug discovery, preclinical development, and clinical development of tofacitinib in-house.

In November 2012, the U.S. Food and Drug Administration (FDA) approved tofacitinib for treatment of rheumatoid arthritis. Two rheumatologists interviewed by the magazine Nature Biotechnology complained that they were “shocked” and “disappointed” at the $2,055 a month wholesale price.

A 2014 study showed that tofacitinib treatment was able to convert white fat tissues into more metabolically active brown fat, suggesting it may have potential applications in the treatment of obesity.

In November 2012, the U.S. FDA approved tofacitinib “to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to, or who are intolerant of, methotrexate.” FDA approved only the 5 mg twice-daily dose on the grounds that a higher dose was not considered to have an adequate risk-to-benefit ratio.

Precautions

• Avoid use of Xeljanz during an active serious infection, including localized infections.
• Use with caution in patients that may be at increased risk of gastrointestinal perforations.
• Laboratory monitoring is recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids.
• Those who take live vaccines must avoid use of Xeljanz.

Long-Term Use Considerations

Because it’s a long-term treatment, it’s important to keep taking tofacitinib (unless you have severe side-effects):

• even if it doesn’t seem to be working at first
• even when your symptoms improve (to help keep the disease under control).

Drug Interactions

Can Interact with the Following

• Strong CP3A4 Inhibitors (e.g., ketoconazole)  
• Moderate CYP3A4 Inhibitors Coadministered with Strong CYP2C19 Inhibitors (e.g., fluconazole)
• Strong CYP3A4 Inducers (e.g., rifampin)  
• Immunosuppressive Drugs (e.g., azathioprine, tacrolimus, cyclosporine)  

Can’t Interact with the Following

NA

When To Stop Taking

Tofacitinib can make you more likely to get infections or may worsen any current infections. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu).

Long-Term Side Effects

The most common adverse effects associated with Xeljanz, which occurred during the first 3 months of use in clinical trials, were upper respiratory tract infections, headache, diarrhea, and nasopharyngitis.

FDA Warnings (History Of)

• February 2019: Safety Trial Finds Increased Risk of Blood Clots in the Lungs and Death with Higher Dose in Rheumatoid Arthritis Patients
• 2018: Warning against use for patients with serious infections
• 2017: Warning against use for patients at risk of gastrointestinal perforations and those who take immunizations.

Other Common Side Effects

NA

Lawsuits

There is no Xeljanz class action pending as of 2019.

Tracy Everhart

Tracy Everhart is the Editor for Drug Law Journal. A highly-trained and certified medical professional, Tracy is also an accomplished medical writer. After spending years on the front lines of the medical profession, Tracy now devotes her expertise and skills to researching and reporting on new drugs and devices that enter the market, as well as their side-effects and the real-life stories involved. Prior to joining Drug Law Journal, Tracy wrote for benchmark online healthcare resources focused on families and, in particular, women’s health issues. Tracy holds post-graduate degrees from both the American College of Healthcare Sciences and the Yale School of Nursing. She is also a graduate of both Hampshire College, where she studied microbiology and the University of South Carolina school of nursing.