Xeljanz FDA Label Warning Update Adds Information About Risk of Cancer, Blood Clots and Heart Side Effects

The FDA has decided to require new label warnings about potential side effects of Xeljanz and other new-generation arthritis drugs from the same class, indicating users may face an increased risk of heart attacks, strokes, cancer, blood clots and death.

In a drug safety communication issued on September 1, the agency announced it has completed a review of a large randomized clinical trial into Xeljanz, determining that side effects may include an increased risk of serious heart-related problems, cancer, pulmonary embolism and fatalities.

As a result of the serious risk, new Xeljanz FDA label warnings are being required to alert the medical community and patients to the potential risks associated with Xeljanz and Xeljanx XR (tofacitinib), which are sold by Pfizer for treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. It was the first member of a new class of treatments known as JAK inhibitors, which also include Olumiant and Rinvoq, which will also be required to carry the heart, cancer and blood clot warnings.

After Xeljanz was introduced in 2012, Pfizer aggressively marketed the drug, joining a lucrative market for rheumatoid arthritis treatments, which already included blockbuster drugs like Humira, Enbrel and other similar medications, known as tumor necrosis factor (TNF) inhibitors. Xeljanz was advertised as a safer and more convenient treatment option, and quickly grew to become a top selling drug, with annual sales of more than $2 billion worldwide. However, data from a recently completed study raised questions about serious Xeljanz side effects that were not adequately described on the drug’s warning label.

In February 2021, the FDA issued a safety communication about a potential link between Xeljanz and cancer, heart attacks and other cardiovascular heart risks, following a preliminary review of data from a recently completed post-marketing study.

The new communication issued this week updates those warnings, following the completion of the FDA’s full safety review. Originally, the agency thought the risks might be only associated with larger doses of Xeljanz. However, now the agency indicates that the same risks appear to exist for users of lower doses of Xeljanz as well.

The FDA also clarified the Xeljanz cancer risk, indicating that there were particularly high rates of certain types of cancers, such as lymphomas and lung cancer, when compared to patients treated with TNF blockers. The higher rate of lung cancer among Xeljanz users appears to be among current or past smokers, compared to current or past smokers who took older TNF blockers.

Other Arthritis Drugs To Carry Similar Warnings

In addition to Xeljanz, the FDA will require new and updated warnings for two other JAK inhibitors, including Olumiant and Rinvoq.

“Olumiant and Rinvoq have not been studied in trials similar to the large safety clinical trial with Xeljanz, so the risks have not been adequately evaluated,” the FDA communication notes. “However, since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.”

The agency noted it did not require warnings of two other JAK inhibitors, Jakafi and Inrebic. They are not indicated for the treatment of arthritis or other inflammatory conditions, and are used to treat blood disorders, which requires different updates to their prescribing information, according to the FDA. However, the agency notes if it becomes aware of any additional safety information or data which warrants updates to their label warnings, it will take further action and alert the public.

The FDA warning requirements come following months of speculation after the agency held up approval of other JAK inhibitors, requiring more study data from the manufacturers.

In June, Abbvie announced expanded approval for Rinvoq was being held up due to similar problems. Before that, in April, Pfizer announced the review for its new oral JAK inhibitor, abrocitinib, had been extended by three months due to the same concerns.

In July, media reports indicated Lilly and Incyte also announced the FDA delayed approval of Olumiant; a rheumatoid arthritis drug seeking expanded approval as an Eczema treatment. It has already been approved to treat the skin condition in 40 countries.

The study behind the FDA’s Xeljanz concerns was initially launched in January 2012, and given the long latency period for many cancers, many users now face concerns they require on-going medical monitoring to detect and diagnose cases in the future.

Former users are now contacting lawyers who are investigating Xeljanz lawsuits and class action claims, to seek additional information which has not been disclosed and compensation for treatments they may now require.