Pfizer’s Xeljanz (tofacitinib) is used to treat rheumatoid arthritis and psoriatic arthritis by relieving pain and swelling in the joints. Xeljanz can also be used to treat symptoms of ulcerative colitis by lowering inflammation. The FDA has warned that taking high doses of Xeljanz can increase the risk of blood clots in the lungs and death.
Xeljanz is an oral prescription medication approved to treat moderately to severely active rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. It also comes in an extended-release formulation, Xeljanz XR.
Both formulations contain the active ingredient tofacitinib. The medication belongs to a class of drugs known as Janus kinase inhibitors or JAK inhibitors.
Pfizer first gained U.S. Food and Drug Administration approval to sell Xeljanz in the United States in 2012. Since its release, the drug has become a blockbuster for Pfizer. In 2018, it brought in about $1.8 billion worldwide.
More than 80 countries approved the medication for the treatment of rheumatoid arthritis (RA). In addition, over 40 countries approved it for the treatment of active psoriatic arthritis (PsA), and 70 countries approved it for the treatment of ulcerative colitis (UC).
From January 2013 to October 2018, doctors prescribed the drug to more than 140,000 people to treat their rheumatoid arthritis, according to the Xeljanz website.
|HOW IT'S TAKEN||Two times a day with or without food||Once a day with or without food|
|DOSAGE||5 mg or 10 mg tablet||11 mg extended release tablets|
|HOW IT'S DELIVERED||Immediate-release tablet that releases medication into the body over the course of several hours||Extended-release tablet that releases medication into the body over the course of a day|
|CAN BE TAKEN WITHOUT METHOTREXATE||Yes||Yes|
Xeljanz Side Effects and Black Box Warning
Despite its popularity, the drug may cause a number of side effects. The side effects reported most often during the first three months of rheumatoid arthritis clinical trials were upper respiratory tract infection, cold-like symptoms, diarrhea, headache and high blood pressure. People who participated in UC clinical trials also reported rashes, Herpes zoster (shingles) and elevated cholesterol levels.
In September 2021 the FDA concluded: “There is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with the arthritis and ulcerative colitis medicines Xeljanz and Xeljanz XR (active ingredient tofacitinib).” Based on these findings from clinical trials that compared Xeljanz to TNF blockers for rheumatoid arthritis, the FDA required a new, stronger black box warning for the drug.
The FDA notified the public in December 2021 that Xeljanz now carries a black box warning for serious infections; a higher rate of lymphoma and lung cancers; a higher rate of death; a higher rate of cardiovascular events (stroke, cardiovascular death and heart attack) and blood clots. The agency also limited the drug’s use to patients who have not responded to or cannot tolerate one or more TNF blockers.
Lawyers are currently filing lawsuits on behalf of patients who suffered these side effects after taking Xeljanz.
How Does Tofacitinib Work?
Xeljanz works by decreasing a substance called cytokines. Cytokines are a protein in the body that helps control the immune system. When our bodies have an infection, cytokines increase to help fight the infection. People with RA make more cytokines than necessary, and this leads to inflammation and pain. Xeljanz disrupts cell signals in the Janus kinase (JAK) pathways to reduce the production of new cytokines, according to a video on the Xeljanz website.
In people with psoriatic arthritis and ulcerative colitis, the drug works the same way to lower inflammation that causes symptoms.
In July 2019, the FDA limited the use of Xeljanz in adults with ulcerative colitis due to safety concerns. The agency had initially approved the drug for the treatment of any adult with moderately to severely active ulcerative colitis. Now the drug is only approved for adults with UC who have an inadequate response or are intolerant to another class of medications called TNF blockers.
Depending on the reason doctors prescribe the drug, it may have different dosage instructions. Patients can take the medicine with or without food.
People may take Xeljanz or Xeljanz XR with or without certain medications called nonbiologic disease-modifying antirheumatic drugs (DMARD) such as methotrexate. But they should not use it with medications called biologic DMARDs or potent immune-suppressing drugs (immunosuppressants) such as azathioprine and cyclosporine.
Patients with severe liver impairment should not use these drugs. Do not take Xeljanz XR for ulcerative colitis.
Xeljanz 5 mg twice daily or Xeljanz XR 11 mg once daily; the recommended dosage for people with moderate and severe kidney impairment or moderate liver impairment is Xeljanz 5 mg once daily.
Psoriatic Arthritis (in combination with nonbiologic DMARDs)
Xeljanz 5 mg twice daily or Xeljanz XR 11 mg once daily; the recommended dosage in patients with moderate and severe kidney impairment or moderate liver impairment is XELJANZ 5 mg once daily.
Xeljanz 10 mg twice daily for at least eight weeks; then 5 mg twice daily. A higher dose of 10 mg twice daily can be continued for a total of 16 weeks, depending on response. Patients should talk to their doctor about stopping the drug if they’ve taken 10 mg twice daily for 16 weeks and they’re not getting the benefits they thought they would. Patients should use the lowest possible dose to maintain the benefits. People with moderate and severe kidney impairment or moderate liver impairment should use half the dose recommended for people with normal liver and kidney function.
Drug Effectiveness and Interactions
Pfizer studied the effectiveness of Xeljanz in patients who took the drug alone or with another DMARD such as methotrexate. The company conducted six studies of more than 4,200 patients with moderate to severe RA.
In clinical studies, medication reduced RA joint pain in as little as two weeks. Though for some patients, the drug may take three to six months to work, according to the Xeljanz website.
In the ORAL Solo Study of patients who took Xeljanz without methotrexate, 30 percent of tofacitinib patients (71 out of 240) experienced a 20 percent reduction in tender and swollen joints after two weeks. In comparison, 12 percent (14 out of 119) of patients in the placebo group experienced the same result.
For ulcerative colitis, the drug can reduce rectal bleeding and stool frequency in as little as two weeks and improve the appearance of the intestinal lining within 8 weeks, according to Pfizer.
Combining Xeljanz and Xeljanz XR with other immune suppressing medicines that treat rheumatoid arthritis, psoriatic arthritis or ulcerative colitis may increase the risk of infection. The drug’s label recommends against taking the medicine in combination with biologic DMARDs or potent immunosuppressants.
- Actemra (tocilizumab)
- Enbrel (etanercept)
- Humira (adalimumab)
- Remicade (infliximab)
- Rituxan (rituximab)
- Orencia (abatacept)
- Kineret (anakinra)
- Cimzia (certolizumab)
- Simponi (golimumab)
- Stelara (ustekinumab)
- Cosentryx (secukinumab)
- Entyvio (vedolizumab)
- Other immunosuppressive drugs
Certain medications that affect liver enzymes, such as rifampin and ketoconazole, may interact with Xeljanz. Depending on the medication, Xeljanz may need to be given at a lower dose or may need to be avoided.
People who plan to take Xeljanz should tell their doctors about all the supplements, vitamins and drugs they take.
FDA Safety Alerts
On Feb. 4, 2021, the FDA released a safety communication about an increased risk of cancer and serious cardiovascular events in people who took Xeljanz in clinical trials.
“Full study results, beyond the co-primary endpoints (including, but not limited to, secondary endpoints such as pulmonary embolism and mortality as well as efficacy data), are not yet available. Pfizer is working with the U.S. Food and Drug Administration (FDA) and other regulatory agencies to review the full results and analyses as they become available,” Pfizer said in a Jan. 21, 2021 press release.
According to initial data reported by Pfizer, the most common cancer reported was lung cancer and the most common cardiovascular event was heart attack. FDA is still investigating this data before taking action.
On Feb. 25, 2019, the FDA released a Safety Communication about an increased risk for blood clots in the lungs, known as pulmonary embolisms, and death in patients who took Xeljanz during a safety trial.
When the FDA approved the drug, it required Pfizer to conduct a clinical trial to evaluate the risk of heart-related events, cancer and opportunistic infections in rheumatoid arthritis patients who take the drug in combination with methotrexate.
The trial was designed to evaluate the treatment at two doses and compare the risks to another drug class called a tumor necrosis factor, or TNF, inhibitor. Examples of drugs in the TNF inhibitor class include Humira, Remicade and Enbrel.
A safety monitoring committee found the increased risk after it reviewed the results from the ongoing study. The increased risk occurred specifically in people with rheumatoid arthritis who took 10 mg of the drug twice daily. The FDA has not approved this dose for people with RA but has approved it in patients with UC.
In a long-term ulcerative colitis extension study, four people had pulmonary embolisms and one patient with advanced cancer died, according to a Dear Healthcare Provider letter.
“Patient safety is of the utmost importance to Pfizer and the company continually monitors the safety of its medicines,” Pfizer’s Chief Medical Officer, Inflammation and Immunology, Dr. Tamas Koncz said in the letter. “As such we continue to work with FDA on this safety signal.”
The FDA continued its investigation, and on July 26, 2019, the agency approved adding a black box warning about an increased risk of blood clots and death.
According to the warning, patients 50 years old and older with RA and at least one cardiovascular risk factor who took 10 mg of Xeljanz twice a day had a higher rate of death, including sudden cardiovascular death, compared to people who took a lower dose or a TNF blocker.
The same group of people also had a higher risk of blood clots, including clots in the lungs known as pulmonary embolisms, clots in deep veins known as deep venous thrombosis and clots in the arteries known as arterial thrombosis.
While the risk was found in people with RA, the FDA is concerned it may also affect people with UC.
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