Xeljanz (tolfacitinib) is a medication used for the treatment of autoimmune disorders including rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.
Autoimmune disorders may develop when the immune system begins to see the body’s own tissues as foreign material and begins to attack them. This may lead to inflammation, pain and destruction of joint and connective tissue, skin tissue, or gastrointestinal tract lining which may result in rheumatoid and psoriatic arthritis, ulcerative colitis, and other conditions.
Xeljanz works to treat autoimmune disorders by blocking an enzyme which contributes to inflammation, known as Janus Kinase (JAK). Blocking of JAK enzyme can help to prevent or reduce the inflammation caused by overactive immune function.
Xeljanz Risk Study
In 2012, Xeljanz was approved for the treatment of RA at the dose of 5mg twice daily. In 2017, use for the treatment of psoriatic arthritis was approved at 5mg twice daily and in 2018, use for the treatment of ulcerative colitis was added at a dose of 5 or 10mg twice daily.
The 2012 approval included a mandate from the FDA requiring a post-marketing safety study which would examine side effects and dosing amounts. The medication had not been approved in the European Union over safety concerns and the FDA’s requirement for additional clinical data was intended to address similar concerns.
The post-marketing study examined adult patients with RA, over the age of 50 who had at least one cardiovascular risk factor such as high blood pressure and who were taking one of three possible regimens:
- Xeljanz 5mg twice daily
- Xeljanz 10mg twice daily
- Anti-TNF medication such as Humira or Remicade
Preliminary study results reported in 2019 showed an increased risk of pulmonary embolism (PE) and deep vein thrombosis (DVT) associated with an increased risk of death in patients taking 10mg twice daily. These patients were switched to the lower 5mg twice daily dose for safety reasons, but final results showed a continued increased risk of death.
In addition to the study results, the FDA had received a number of serious adverse event reports citing PE and DVT and including some deaths. This prompted the FDA to issue a February 2019 safety alert warning of the increased risk of PE, DVT and VTE-associated death in patients taking Xeljanz and required Pfizer to update Xeljanz prescribing information.
In February of 2021, additional results showed that patients who took Xeljanz had an increased risk of serious heart-related events and cancer, both of which may be life-threatening. The risk was apparent with both the 10mg twice daily dose and at the lower 5mg twice daily dose. Based on the second set of preliminary results, the FDA issued another safety alert regarding Xeljanz and Xeljanz XR.
Pulmonary Embolism and Deep Vein Thrombosis
A venous thromboembolic event is a blood clot that develops in the veins such as pulmonary embolism or deep vein thrombosis.
Pulmonary embolism occurs when a blood clot forms or becomes lodged in the lungs. Symptoms of PE may include:
- Chest pain
- Irregular heartbeat
- Shortness of breath
- Dizziness or fainting
- Sweating or clammy skin
- Coughing up blood
Deep vein thrombosis occurs when a blood clot forms or becomes lodged in a deep vein, most often in the legs. Symptoms of DVT may include:
- Pain and tenderness in affected area
- Swelling in affected area
- Redness in affected area
Any symptoms of DVT or PE should be reported a health care professional right away. Sudden or severe symptoms may warrant emergency treatment.
Xeljanz Warnings and Side Effects
Though Xeljanz was approved for use in the U.S. in 2012, use in the EU was denied over concerns of risks including cancer, high blood pressure, liver damage, stomach bleeding and infection. The FDA requires a “black box warning” to be included on all prescribing information for Xeljanz or Xeljanz XR which warns of the risk of serious infections and malignancies or cancers that may occur with Xeljanz use.
New safety results warning of heart attack and cancer risk have not yet been included on Xeljanz prescribing information or prescription labels, however many in the industry expect that additional restrictions may be forthcoming.
All medications may cause side effects, most of which are mild to moderate and will go away with time. Others may be more severe or even serious and life-threatening.
Xeljanz common side effects may include:
- Upper respiratory infection
- Nasal or cold symptoms
- Increased blood pressure
Xeljanz severe side effects may include:
- Serious infections including bacterial, viral and fungal infections
- Lymphomas or other types of cancer
- Reactivation of Hepatitis or Herpes viral infection
- Gastrointestinal perforation
- Allergic or hypersensitivity reaction
- Venous thromboembolic event such as PE or DVT
Persistent or bothersome side effects should be reported to a health care professional. Serious side effects, symptoms of PE or DVT or sudden symptoms should be reported right away and may require emergency medical attention.
Xeljanz (tofacitinib) is approved to treat rheumatoid arthritis, ulcerative colitis and psoriatic arthritis but may increase the risk of venous thromboembolic event (VTE) or blood clot formation in the veins. The increased risk may include events such as pulmonary embolism (PE) in the lungs and deep vein thrombosis (DVT) in the legs or extremities, both of which may be serious or life-threatening.
The U.S. Food and Drug Administration (FDA) issued a February 2019 safety alert which warned of the increased risk of PE or DVT in patients who had taken Xeljanz 10mg twice daily. Health professionals were advised that Xeljanz 10mg dosing was not approved for RA or PsA and should only be used in UC patients who had not responded to other medications.
The initial study results also indicated that some increase in risk was also seen in patients taking a lower dose of 5mg twice daily. This was confirmed with the February 2021 safety alert which warned of an increased risk of heart-events and cancer in patients taking both 10mg twice daily and those taking 5mg twice daily.
The FDA has required that Pfizer update Xeljanz and Xeljanz XR prescribing information to include the increased risk of VTE, DVT and PE but reports indicate that the drug has been responsible for hundreds of serious injuries and several deaths.
Current black box warning information states that the medication may increase the risk for:
- Serious infections including tuberculosis, invasive fungal infections, opportunistic pathogens including herpes zoster and other viruses or bacteria
- Risk of death in patients with cardiovascular risk factor.
- Lymphoma and other cancer types.
- Blood clots including pulmonary embolism (PE), deep vein thrombosis (DVT) and arterial thrombosis.
Pfizer may be facing Xeljanz lawsuits for injuries and deaths caused by the medication.
Xeljanz PE and DVT Effects
Xeljanz labeling did not initially include warnings about blood clot formation but prescribing information has been updated to warn of venous thromboembolic events (VTE), deep vein thrombosis (DVT) or pulmonary embolism (PE).
Symptoms of DVT may include:
- Pain in lower leg (or other affected area)
- Swelling in lower leg
- Warmth in affected area
- Redness or discoloration of skin in affected area
Symptoms of PE may include:
- Shortness of breath
- Chest or back pain
- Coughing with bloody discharge
- Clammy skin
- Pale, gray or bluish appearance
Venous thromboembolic events may sometimes occur without warning or symptoms but may lead to sudden death in severe cases. All symptoms should be reported to a health care provider immediately. Sudden or severe symptoms should be treated as a medical emergency.
Filing a Xeljanz Lawsuit
People or loved ones of those who took took Xeljanz for RA, PSA or UC and suffered injury or death may be filing lawsuits against Pfizer, manufacturer of Xeljanz and Xeljanz XR.
Injuries named in lawsuits may include:
- Heart attack
- Ischemic stroke
- Breast cancer
- Lung cancer
- Pancreatic cancer
- Prostate cancer
- Pulmonary embolism (PE)
- Deep vein thrombosis (DVT)
People or loved ones of those who have been injured after taking Xeljanz should seek legal assistance.
Notwithstanding claims relating to this product, the drug/medical device remains approved by the U.S. FDA.
- Xeljanz Prescribing Information, Drugs.com (2020)
- Initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib), U.S. Food and Drug Administration (02/2021)
- FDA weighs tighter restrictions for Pfizer’s Xeljanz on the heels of safety red flags, Fierce Pharma (02/2021)
- Safety trial finds risk of blood clots in the lungs and death with higher dose of tofacitinib (Xeljanz, Xeljanz XR) in rheumatoid arthritis patients; FDA to investigate, U.S. Food and Drug Administration (02/2019)