Skin Cancer Risk Linked to Xeljanz, Jakafi, Other JAK Inhibitors: Study

Amid increasing concerns in recent years over the side effects of Xeljanz and other JAK inhibitors, which have been linked to an increased risk of cancer, heart attacks, strokes and deadly blood clots, the findings of a new study suggest that the new-generation arthritis treatments may also carry a skin cancer risk.

Xeljanz (tofacitinib) was introduced by Pfizer in 2012, as the first member of the JAK inhibitors class of medications, which joined a lucrative market that generates billions in annual sales for treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis.

Last year, the FDA announced new label warnings about the Xeljanz heart and cancer risks, after evaluating data from a large randomized clinical trial funded by the drug maker, which found users of the drug experienced more cardiovascular events, as well as cancers, pulmonary embolism and death. As a result of the findings, the agency required a label update for Xeljanz, as well as all other drugs in the same new class of medications.

In a new study published this month in the medical journal Therapies, French researchers say they have also found an association between the class of medications known as Janus kinase (JAK) inhibitors and skin cancer, including melanoma, squamous cell carcinoma and Merkel cell carcinoma.

Researchers indicate that incidents of skin cancer have been reported among patients taking Xeljanz, Jakafi and similar medications, but those risks were not seen in clinical trials used to gain approval for the drugs’ use.

To verify the reports, researchers used data from the World Health Organization’s Vigibase international database of suspected adverse drug reactions. They investigated all reports of skin cancers submitted to the French Pharmacovigilance database from 1978 until the end of 2019 linked to Xeljanz, Jakafi and Olumiant. The specifically looked for incidents of melanoma, squamous cell carcinoma and Merkel cell carcinoma.

The study found an increased risk linked to all three forms of cancer with the drugs Xeljanz and Jakafi, but only found an increased risk of Merkel cell carcinoma linked to the use of Olumiant, which is another member of the same class. Merkel cell carcinoma risks were more prevalent in immunosuppressed patients and was “associated with a significant disproportionality signal with all the studied JAK inhibitors” the researchers found.

“Our study shows that JAK inhibitors could be associated with an extra risk to develop skin cancers,” the researchers concluded. “Considering pharmacovigilance method limitations, further pharmacoepidemiological studies are required to assess a causal link between JAK inhibitors treatment and skin cancer development.”

After Xeljanz was introduced, Pfizer aggressively marketed the drug, hoping to take over some of the lucrative market for rheumatoid arthritis treatments, which already included blockbuster drugs like Humira, Enbrel and other 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, concerns about serious Xeljanz side effects first emerged in February 2021, after preliminary data was released from a post-marketing study conducted by the drug maker.

There are now a growing number former users pursuing a Xeljanz lawsuit against the drug maker, after being diagnosed with cancer, heart attacks, strokes, pulmonary embolism, deep vein thrombosis or other injuries that may have been avoided if earlier warnings had been provided about the potential side effects.