Xeljanz

Approved Uses

Xeljanz is used to treat adults and some children with the following conditions:

• Rheumatoid Arthritis: For adults with moderately to severely active rheumatoid arthritis when methotrexate has not worked well enough.
• Psoriatic Arthritis: For adults with active psoriatic arthritis when methotrexate or other similar medicines have not worked well enough.
• Ankylosing Spondylitis: For adults with active ankylosing spondylitis who have not responded well to or cannot tolerate certain other medications called tumor necrosis factor (TNF) blockers.
• Ulcerative Colitis: For adults with moderately to severely active ulcerative colitis when TNF blockers have not worked well or were not tolerated.
• Polyarticular Juvenile Idiopathic Arthritis: For children 2 years of age and older with active polyarticular juvenile idiopathic arthritis.

This medication is often reserved for patients who have already tried other treatments, such as methotrexate or TNF blockers, without success or because of side effects.

Mechanism of Action

Xeljanz belongs to a class of medications known as Janus kinase (JAK) inhibitors. It works by targeting specific pathways inside the body's immune cells to help control inflammation.

Blocking JAK Enzymes

In many autoimmune conditions, the immune system is overactive and produces too many inflammatory signals. These signals rely on enzymes called Janus kinases (specifically JAK1, JAK2, and JAK3) to communicate. These enzymes act like internal switches that, when turned on, tell the cell to produce proteins that cause inflammation.

Xeljanz works by:

• Entering the cell and binding to these JAK enzymes.
• Interfering with the signaling process that triggers an immune response.
• Reducing the production of cytokines, which are the proteins responsible for causing swelling, pain, and tissue damage.

Difference from Biologics

While Xeljanz affects the immune system in a way similar to biologic medications, it works differently. Biologics are large proteins that usually target inflammatory signals outside of the cells. Xeljanz is a small-molecule drug that works from the inside of the cell. Because of its smaller size, it can be taken orally as a tablet rather than through an injection or infusion.

Common Side Effects

Some people taking Xeljanz may experience mild side effects. Common symptoms include:

• Upper respiratory tract infections (such as the common cold or sinus infections)
• Headache
• Diarrhea
• Nasal congestion, sore throat, or runny nose
• High blood pressure

Serious Side Effects

Xeljanz can cause serious side effects that may require medical intervention. These include:

• Serious Infections: Increased risk of tuberculosis, shingles, and other bacterial, fungal, or viral infections due to a weakened immune system.
• Heart Problems: Increased risk of major cardiovascular events, including heart attack and stroke, particularly in those with existing risk factors.
• Blood Clots: Development of clots in the lungs, legs, or arteries.
• Cancer: Increased risk of certain malignancies, such as lymphoma and lung cancer.
• Gastrointestinal Perforation: Tears in the stomach or intestines, especially in patients also taking NSAIDs or corticosteroids.
• Liver Damage: Signs may include yellowing of the skin or eyes (jaundice) and dark urine.
• Allergic Reactions: Severe skin rash, swelling of the face or tongue, or trouble breathing.

Boxed Warnings

Xeljanz includes several boxed warnings, the most serious type of warning required by the FDA. These warnings highlight significant risks for certain patients:

• Serious Heart-Related Events: There is an increased risk of major cardiovascular events, such as heart attack or stroke, particularly in patients who are current or former smokers.
• Cancer: Use of this medication may increase the risk of developing certain cancers, including lymphoma and lung cancer.
• Blood Clots: There is an increased risk of blood clots in the lungs and deep veins, which can be life-threatening. This risk is higher with the 10 mg twice-daily dose.
• Serious Infections: Xeljanz can weaken the immune system, making it harder to fight infections. Serious infections, including tuberculosis and those caused by bacteria, fungi, or viruses, have occurred and may lead to hospitalization or death.
• Increased Risk of Death: Clinical trials found a higher rate of death from all causes in patients 50 years and older with at least one heart-related risk factor.

Other Precautions

In addition to the boxed warnings, other safety considerations include:

• Gastrointestinal Perforation: Some patients have experienced tears in the stomach or intestines while taking this medication.
• Laboratory Monitoring: Regular blood tests are typically required to monitor for changes in white blood cell counts, red blood cell counts (anemia), liver enzyme levels, and cholesterol.
• Vaccinations: It is generally recommended to avoid live vaccines while taking Xeljanz.
• Liver Health: This medication is generally not recommended for patients with severe liver impairment.

Pregnancy

There is limited information regarding the safety of Xeljanz during pregnancy. It is not yet known if the medication can cause harm to an unborn baby. Healthcare providers typically recommend using this medication during pregnancy only if the potential benefit justifies the potential risk to the fetus.

If you are pregnant or planning to become pregnant, you should inform your doctor before starting or continuing treatment. There may be pregnancy registries available to monitor the health of individuals and their babies after exposure to the medication during pregnancy.

Breastfeeding

It is not known whether Xeljanz passes into human breast milk. However, because of the potential for serious adverse reactions in a nursing infant, breastfeeding is generally not recommended while taking this medication.

Specific guidelines for when it may be safe to breastfeed after stopping the medication include:

• Immediate-release tablets or oral solution: Wait at least 18 hours after the last dose.
• Extended-release tablets: Wait at least 36 hours after the last dose.

Available Forms

Xeljanz is administered orally and is available in the following forms:

• Tablets: Immediate-release tablets for standard oral administration.
• Extended-release tablets: These tablets, often labeled as Xeljanz XR, are designed to release the medication slowly into the body.
• Oral solution: A liquid form of the medication for oral use.

FDA Approval and Indications

Xeljanz (tofacitinib) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of several inflammatory conditions, including:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ulcerative colitis
• Ankylosing spondylitis
• Polyarticular juvenile idiopathic arthritis

Boxed Warning

The FDA requires a Boxed Warning for Xeljanz, which is the agency's most serious type of warning. This warning was implemented and later updated following clinical trial results that identified significant safety concerns. The Boxed Warning includes information regarding:

• Serious heart-related events: An increased risk of heart attack, stroke, and cardiovascular death, particularly in patients who are current or past smokers.
• Cancer: An increased risk of certain cancers, including lymphomas and lung cancer.
• Blood clots: A higher risk of blood clots in the lungs (pulmonary embolism) and deep veins.
• Death: An increased risk of death from all causes compared to patients taking TNF blockers.
• Infections: A risk of serious bacterial, fungal, viral, and opportunistic infections that may lead to hospitalization or death.

Regulatory History and Safety Communications

In 2021, the FDA required updates to the Xeljanz prescribing information based on the final results of a large safety clinical trial. This trial compared Xeljanz to another class of drugs called tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis who were at least 50 years old and had at least one cardiovascular risk factor. The study found that Xeljanz carried a higher risk of serious heart-related events and cancer than TNF blockers.

The FDA has also issued specific warnings regarding dosage. The 10 mg twice-daily dose is only approved for the initial treatment of ulcerative colitis and for limited maintenance use in certain patients, as higher doses have been linked to an increased risk of blood clots and death.

Insurance Coverage

Xeljanz is a brand-name prescription medication. Most health insurance plans, including Medicare, provide coverage for it, but the specific out-of-pocket cost depends on the plan's formulary and benefit structure. Many insurance companies require prior authorization before approving coverage for this medication.

Factors Affecting Price

Several factors can influence the final cost of Xeljanz:

• Formulation: The price may differ between the immediate-release tablets, the extended-release (XR) tablets, and the oral solution.
• Pharmacy Choice: As a specialty medication, Xeljanz is often dispensed through specialty pharmacies, which may have different pricing or delivery arrangements compared to retail pharmacies.
• Dosage: The strength and frequency of the dose prescribed for conditions like rheumatoid arthritis, psoriatic arthritis, or ulcerative colitis can impact the total cost.

Generic Availability

Xeljanz is currently available as a brand-name drug. Because there is limited generic competition for this specific Janus kinase (JAK) inhibitor, the cost typically remains higher than that of older, non-biologic disease-modifying antirheumatic drugs (DMARDs).