Xeljanz can cause serious complications, side effects, and injuries to the people who take the drug for their arthritis or colitis. It was only in July of 2019 that the FDA ordered Pfizer, the manufacturer of Xeljanz, to update the drug’s warning label to adequately notify doctors and patients of the risks.
The lawyers at the Shouse Law Office can legally represent victims of Xeljanz and help them file a claim for compensation before the statute of limitations expires on their case. In this article, they explore:
- 1. What is Xeljanz?
- 2. Side effects of Xeljanz
- 3. Xeljanz can cause cancer
- 4. Xeljanz can cause liver damage
- 5. Xeljanz can cause blood clots in the lungs and pulmonary embolisms
- 6. Medical complications and injuries of the side effects of Xeljanz
- 7. Xeljanz lawsuits claim Pfizer failed to adequately warn of the dangers
1. What is Xeljanz?
Xeljanz is the brand name of the drug tofacitinib, which was designed and is manufactured by the giant drug company Pfizer. Xeljanz has been approved by the U.S. Food and Drug Administration (FDA) to treat several ailments:
- Rheumatoid arthritis on November 6, 2012,1
- Psoriatic arthritis on December 14, 2017,2 and
- Ulcerative colitis on May 30, 2018.3
Xeljanz works by slowing down the chemical reactions caused by Janus kinase enzymes, also known as JAK enzymes. JAK enzymes play a pivotal role in the replication of cells inside the body. This can create a problem if JAK enzymes cause cells to replicate and spread too quickly, though.
When cell growth happens too fast in joints, it can create unnecessary tissues that damage the bone structure and cartilage that facilitate joint movement. To exacerbate the problem, the body’s immune system sees the new tissue as a threat to be removed and attacks it. Together, the inflammation in the joint can cause a debilitating and chronically painful condition known as rheumatoid arthritis.
By inhibiting the underlying problem of the JAK enzymes, Xeljanz can treat rheumatoid arthritis. Its effectiveness against JAK enzyme activity can also be used to treat psoriatic arthritis and ulcerative colitis, as well.
When it was first released, Xeljanz became a popular treatment for rheumatoid arthritis because earlier drugs had to be injected. Xeljanz, on the other hand, comes in a pill form and has two dosing and administration options:
- Xeljanz, which comes in tablets of 5 milligrams and should be taken twice a day, depending on the patient’s kidney and liver history, and
- Xeljanz XR, which stands for “extended release,” an 11-milligram tablet taken once a day that delays the drug’s release throughout the day.
2. Side effects of Xeljanz
Like many drugs, Xeljanz can cause some common side effects, including:
- High blood pressure,
- Sinus infections,
- Upper respiratory tract infections,
- Neutropenia, or the medical condition of a low white blood cell count, and
Among the most common side effects of Xeljanz are signs and symptoms often confused with the common cold, like:
- Sore throat,
- Runny nose,
- Nasal congestion, and
However, there are also some far more severe side effects of taking Xeljanz:
- Malignant cell growth, including cancer,
- Liver damage, and
- Blood clots traveling to the lungs, where they can cause a pulmonary embolism.
Some of these severe side effects are emergency events that can be fatal. Others can drastically shorten a victim’s life expectancy and cause long-term debilitation.
3. Xeljanz can cause cancer
Studies and several clinical trials have found that Xeljanz can lead to cancer. Possibly because Xeljanz interacts with JAK enzymes, which influence how a variety of cells replicate rather than a particular type of tissue, Xeljanz has been known to cause numerous different types of cancer rather than just one4:
- Lung cancer,
- Breast cancer,
- Gastric cancer,
- Non-melanoma skin cancer,
- Prostate cancer, and
- Pancreatic cancer.
Some of Pfizer’s own clinical trials have shown that Xeljanz carries a relatively high risk of developing cancer. There were 19 clinical trials, in all, spread into three phases and long-term extension trials:
- Phase I: 2 clinical trials,
- Phase II: 9 clinical trials,
- Phase III: 6 clinical trials, and
- 2 long-term extension trials
Phases I-III covered 5,497 participants who were taking Xeljanz, which the long-term extension trials continued to monitor 2,794 of these participants.
Two meta-analyses tracked many of the results of these clinical trials – because the studies were published while some of the clinical trials were ongoing, not all of the results could be included.5 What these two medical studies found, though, was that clinical trial participants taking Xeljanz were developing malignancies and cancer at a far higher rate than those in the placebo or comparator arm.
One of the studies only looked at whether someone taking Xeljanz developed cancer or another malignancy during the trial. It found that:
- 6,194 people took Xeljanz over the course of the trials,
- 173 got cancer, and
- Another 118 developed a non-melanoma skin cancer.
That study refused to report data on placebo-takers in the clinical trials, though, because its authors found the duration for placebo treatment was too short.6
The other study, however, did compare Xeljanz participants to the placebo group, and also broke down the malignancies into types of cancer. According to that study, the clinical trials involved:
- 5,671 people taking Xeljanz,
- 118 of whom developed non-melanoma skin cancer, and
- 107 of whom got cancer, including:
- 24 with lung cancer,
- 19 with breast cancer,
- 10 with lymphoma, and
- 6 with gastric cancer.
Meanwhile, zero trial participants in the placebo arm got cancer.7
Pfizer, meanwhile, has maintained that these results are because people with rheumatoid arthritis are already at heightened risk for cancer.
4. Xeljanz can cause liver damage
Xeljanz can also cause liver damage.8 The risks are especially high if Xeljanz is being taken alongside the drug methotrexate and mixed with alcohol.
During the clinical trials for Xeljanz, doctors monitored the serum enzyme levels of participants, including:
- Alanine transaminase, or ALT
- Aspartate transaminase, or AST, and
Together, these readings are used as biomarkers for healthy livers. When they increase or decrease, doctors know to look for other signs of a damaged or compromised liver.
A post hoc study analyzed 25 different clinical trials and other medical studies dealing with Xeljanz. It compared the ALT, AST, and bilirubin levels of people taking Xeljanz to those in the placebo arm, noting whether their levels were above the upper limits of normal (ULN) or more than three times the ULN. It found strong signs that Xeljanz was connected to liver damage9:
|Group Taking Xeljanz (8,115)||Group on Placebo (1,841)|
|ALT Above the ULN||20.9%||15.7%|
|ALT Three Times Above the ULN||1.2%||0.8%|
|AST Above the ULN||15.0%||9.6%|
|AST Three Times Above the ULN||0.6%||0.5%|
|Total Bilirubin Above the ULN||3.3%||2.3%|
Two other clinical studies of Xeljanz fell in line with these findings:
- One clinical trial found that only 4% of placebo-takers had ALT readings above the ULN, compared to 19% of people taking Xeljanz, including 3% that were more than three times the ULN,10 and
- Another clinical trial found that people taking higher doses of Xeljanz were progressively more likely to have ALT levels more than three times over the ULN.11
5. Xeljanz can cause blood clots in the lungs and pulmonary embolisms
Perhaps the most prominent side effect of Xeljanz is the possibility of a blood clot traveling to a patient’s lungs and causing a pulmonary embolism. The risks are especially dire for patients who have been taking high doses of Xeljanz.
As a part of its initial approval of Xeljanz, the FDA required Pfizer to conduct a post-marketing study to see if Xeljanz was a cardiovascular risk for people who already had heart problems.12
The resulting post-marketing study was Study A3921133.13 It included people taking a variety of Xeljanz doses to a comparator group taking a tumor necrosis factor inhibitor drug.
However, Pfizer intervened in the study before it was over when it learned that certain participants in the study were having blood clots in their lungs and suffering from pulmonary embolisms at alarming rates. In particular, participants who were taking 10-milligram doses of Xeljanz twice every day were having these blood clots and embolisms more than five times as often as those taking the tumor necrosis factor inhibitor drug, and three times as often as people taking the standard dose of Xeljanz.14
On February 19, 2019, Pfizer intervened and shifted the people taking 10-milligram doses twice a day into the arm of participants taking 5-milligram doses twice daily.15 It was not until after the FDA caught wind of the change and issued a safety warning of its own on February 2516 that Pfizer issued a press release three days later to outline the change in the clinical trial.17
The significance of these findings from Study A3921133 are profound because the 10 milligrams, twice-daily dose of Xeljanz has been approved by the FDA for people who take the drug to treat their ulcerative colitis. The clear risks of developing a blood clot in the lungs and suffering from a pulmonary embolism, however, are not mentioned in Xeljanz’s warning label.18
6. Medical complications and injuries of the side effects of Xeljanz
Altogether, these serious side effects of Xeljanz pose a danger to patients, and can cause severe medical complications and debilitating or even fatal injuries to people who take the drug.
6.1 Complications and injuries of people who have gotten cancer
Cancer is a frequently fatal condition. However, even when it is not terminal, the physical and financial toll of overcoming it can be debilitating. Depending on the type of cancer, it can involve:
- Surgery, and
- In the case of breast cancer, permanent disfigurement.
For many victims of cancer, fighting the disease takes years out of their lives and shortens their life expectancy considerably. Even if they do beat it and their treatments send the cancer into remission, there is always the potential of it returning.
6.2 Complications and injuries of liver damage
The liver provides a crucial service in the body: It filters blood and removes impurities in it. If it gets damaged, those impurities can build up and cause a myriad number of medical conditions elsewhere in the body. Liver damage that continues unchecked can lead to chronic liver failure, or cirrhosis.
Chronic liver failure can be fatal. It can also cause other medical problems, including:
- Serious infections as the immune system weakens without the help of the liver,
- Spontaneous bacterial peritonitis, and
- Blood sodium problems, including hepatorenal syndrome.
6.3 Injuries and complications of pulmonary embolisms and blood clots in the lungs
When a blood clot reaches your lungs, it can create a pulmonary embolism – an emergency medical condition that requires immediate care.
One medical study found that an estimated one in four people who do not get adequate treatment for a pulmonary embolism died from the condition.19 Another study estimates that more than 50,000 people die of pulmonary embolisms every year in the U.S.20
Even if there is prompt medical care, blood clots that reach the lungs can cause serious medical complications down the road. Some of them are:
- A heightened risk for another blood clot to reach the lungs and cause another pulmonary embolism,
- Diminished oxygen levels in the blood, and
- Lungs damage, including the death of lung tissue.
7. Xeljanz lawsuits claim Pfizer failed to adequately warn of the dangers
Because these side effects are so poorly mentioned in the warning label for Xeljanz, numerous lawsuits have been filed against Pfizer for their failure to warn doctors and patients of the risks of taking the drug.
These lawsuits demand compensation for the injuries and other losses that victims have sustained, through this lack of an adequate warning:
- Medical expenses,
- Pain and suffering,
- Loss of a family’s consortium, and
- Professional repercussions of a long and arduous recovery process.
They also seek punitive damages in order to punish Pfizer for their culpable conduct.
While these Xeljanz lawsuits are still proceeding individually, it seems likely that they will be consolidated into a multidistrict litigation, or MDL, in the near future.
- FDA Approval Letter for Xeljanz (November 6, 2012).
- Press Release, “Pfizer Announces FDA Approval of Xeljanz® (tofacitinib) and Xeljanz® XR for the Treatment of Active Psoriatic Arthritis,” Pfizer, (December 14, 2017).
- FDA Approval Letter for Xeljanz to Treat Ulcerative Colitis (May 30, 2018).
- Xeljanz Warning Label (May 2018).
- Cohen SB, Tanaka Y, Mariette X, et al., “Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials,” Annals of the Rheumatic Diseases 76(7):1253-1262 (2017) and Curtis JR, Lee EB, Kaplan IV, et al., “Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme,” Annals of the Rheumatic Diseases 75(5):831-41 (2016).
- Cohen SB, Tanaka Y, Mariette X, et al., “Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials,” Annals of the Rheumatic Diseases 76(7):1253-1262 (2017).
- Curtis JR, Lee EB, Kaplan IV, et al., “Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme,” Annals of the Rheumatic Diseases 75(5):831-41 (2016).
- See generally, Berhan A, “Efficacy, safety and tolerability of tofacitinib in patients with an inadequate response to disease modifying anti-rheumatic drugs: a meta-analysis of randomized double-blind controlled studies,” BMC Musculoskeletal Disorders 14:332 (November 26, 2013).
- Soriano ER, Madariaga H, Castañeda O, Citera G, Schneeberger EE, Cardiel MH, Hendrikx T, Graham D, Shi H, Ponce de Leon D, “FRI0099 Liver enzyme abnormalities after tofacitinib treatment in patients with hepatic steatosis from the rheumatoid arthritis, psoriatic arthritis and psoriasis clinical programmes,” Annals of the Rheumatic Diseases 77(2):593-4 (June 15, 2018).
- ClinicalTrials.gov Identifier No. NCT00603512, “Comparison Of 4 CP-690,550 Doses Vs. Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid Arthritis in Japan,” published at Tanaka Y, Suzuki M, Nakamura H, Toyoizumi S, Zwillich SH, “Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate,” Arthritis Care and Research 63(8):1150-8 (August 2011).
- Kremer JM, Cohen S, Wilkinson BE, Connell CA, French JL, Gomez-Reino J, Gruben D, et al., “A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone,” Arthritis and Rheumatism 64(4):970-81 (April 2012).
- See Press Release, “Increased risk of pulmonary embolism and mortality in rheumatoidarthritis patients receiving 10mg twice daily in a clinical trial,” Pfizer (March 26, 2019).
- ClinicalTrials.gov Identifier No. NCT02092467, “Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis.”
- See note 12.
- Press Release, “Communication of new safety information for XELJANZ (tofacitinib),” Pfizer (February 28, 2019).
- FDA Drug Safety Communication, “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,” (February 25, 2019).
- See note 15.
- See note 4.
- Barritt DW, Jordan SC, “Anticoagulant Drugs in the Treatment of Pulmonary Embolism,” The Lancet 275(7138):1309-12 (June 18, 1960).
- See Rahimtoola A, Bergin JD, “Acute pulmonary embolism: an update on diagnosis and management,” Current Problems in Radiology 30(2):61-114 (February 2005); Allison Prang, “FDA Requires Box Warnings for Pfizer Drug Xeljanz Patients taking 10-milligram dose twice a day could experience a higher risk of blood clots or death,” Wall Street Journal (July 26, 2019).