FDA Requires Additional Warnings for JAK Inhibitors about Adverse Health Effects

The U.S. Food and Drug Administration (FDA) has issued yet another safety communication to patients and health care providers about their revisions to the Boxed Warning due to conclusions of an increased risk of serious heart-related problems and cancer with the use of Janus Kinase (JAK) inhibitors. The FDA is now requiring new and expanded warnings for three approved rheumatoid arthritis treatments in the same drug class - Xeljanz, Olumiant, and Rinvoq.

The agency’s decision stems from the final review of a widescale safety clinical trial of Xeljanz. The manufacturer, Pfizer’s trial of the arthritis and ulcerative colitis medicine compared Xeljanz to another arthritis treatment called tumor necrosis factor (TNF) inhibitors. A prior safety alert based upon earlier trial results reported an increased risk of serious health concerns at a higher dosage. This was later dismissed and shown to exhibit the same level of risk at a lower dosage as well. Xeljanz has been found to drastically increase the possibility of:

• Blood clots in the lungs;
• Deep vein thrombosis (DVT);
• Serious infection;
• Heart-related problems;
• Cancer;
• Liver damage;
• Pulmonary embolisms (PE), and
• Death.

JAK inhibitors are the latest drug class of disease-modifying medication to emerge for the treatment of serious, chronic inflammatory diseases, such as rheumatoid arthritis (RA). It is an oral solution that works by interfering with the inflammatory processes within the immune system that cause the symptoms of RA. JAK inhibitors have proved to be especially popular because it is taken as a pill, unlike other treatments which must be injected.

Xeljanz was the first of its kind, making way as a relatively new group of medicine. Xeljanz or tofacitinib was first approved in 2012 to treat adults with RA who did not respond well to other medications. But it was soon faced with apprehension:

July 2013: A randomized clinical trial began with the primary objective to compare the efficiency and safety of Xeljanz at two doses (5 mg twice daily and 10 mg twice daily) to TNF inhibitors for those with rheumatoid arthritis.

December 2017: The FDA approved the drug for patients suffering from psoriatic arthritis (PsA). PsA is a form of arthritis that affects some people who have psoriasis, causing joint pain, stiffness, and swelling in any part of the body.

May 2018: Tofacitinib is approved by the FDA to additionally treat ulcerative colitis, an inflammatory bowel disease that causes inflammation and sores in the digestive tract.

Xeljanz and other JAK kinase inhibitors are a relatively new group of medicine, so not all side effects and risks are known. Because of this, the FDA required Pfizer to conduct a post-marketing safety study of tofacitinib.

January 2019: The interim results of the trial identified 19 cases of blood clots in the lungs out of the 3,884 patients who received tofacitinib 10 mg twice daily compared to the 3 cases out of the TNF blockers comparison group. Additionally, 45 patients in the tofacitinib patient group died in contrast to the 25 deaths in those who received TNF blockers.

February 2019: The FDA released their first alert communication after the drug manufacturer, Pfizer, intervened to take patients off the 10 mg twice daily dose. This came following an external safety committee notifying a disturbingly high number of people taking the higher dosage developed blood clots in their lungs and experienced pulmonary embolisms.  

July 2019: After reviewing preliminary data from the continuing safety clinical trial, the FDA approved new warnings about the use of a 10 mg daily dosage, including adding their prominent boxed warning. Boxed warnings, or “black box warnings”, are the strictest warning that can be issued for a drug by the FDA, used to alert doctors to very serious side effects of a medication or to place restrictions on its use.

February 4, 2021: The agency issued another drug safety communication confirming and elaborating on previous findings after the clinical trial concluded, stating that initial results “showed an increased risk of serious heart-related problems and cancer with the arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib).” This information is in addition to previous warnings about blood clots, infections, and cancer. But unlike prior alerts, the FDA includes warnings about both the 10mg twice-daily dose and 5 mg bi-daily prescription.

September 1, 2021: Based on the final review of a widescale safety clinical trial, FDA requires warnings about the increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors. The study’s results confirmed their interim finding of Xeljanz at all dosages leading to the revisions of black box warnings for Xeljanz and two other arthritis prescriptions, Olumiant (baricitinib) and Rinvoq (upadacitinib) to include material about the associated risks.

If you or a loved one believe you have been harmed by a JAK inhibitor, contact our experienced product liability team to get the help you deserve.  At Meyers & Flowers, our track record of large resolutions for victims of dangerous drugs is a testament to the representation you will receive. With no fees, unless we win, contact us today for a free case evaluation at (630) 232-6333, [email protected], or on our website.