USA – The Food and Drug Administration (FDA) has added strictest warnings to the labels of JAK inhibitors, a class of drugs used to treat arthritis manufactured by Pfizer, Eli Lilly, and AbbVie, citing the risk of serious health problems and death in patients aged 50 and up.

The FDA reviewed Pfizer’s Xeljanz after preliminary findings from a February trial revealed an increase in serious health-related problems and cancer in some patients taking the drug, according to the FDA. As a result, the warning has been added to the labels.

The drugs are anti-inflammatory medications, and the study found an increased risk of blood clots and death.

There have been no large safety clinical trials for Eli Lilly’s Olumiant or AbbVie’s Rinvoq, but because they share mechanisms of action with Xeljanz, the FDA believes these medicines may pose similar risks, according to the agency.

Rinvoq, an AbbVie rheumatoid arthritis drug, and Xeljanz, a Pfizer rheumatoid arthritis drug, are now only recommended for use in patients who have had an inadequate response or intolerance to one or more Tumor Necrosis Factor (TNF) blockers, which are another class of drugs used to treat inflammatory conditions.

The FDA’s boxed warnings on the labels of Rinvoq, Xeljanz, and Lilly’s Olumiant highlight the risk of cardiovascular death and stroke in high-risk patients aged 50 and older who are current or former smokers.

Their labels now include additional information about the risk of certain types of cancer and death.

The FDA is still reviewing marketing applications for Rinvoq’s expanded use in atopic dermatitis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis, according to AbbVie.

When it all started

The JAK safety saga began with alarming findings in a post-marketing study of Xeljanz in rheumatoid arthritis patients with pre-existing cardiovascular risk factors.

Patients taking the Pfizer drug had an increased risk of blood clots, major heart-related event death, death, and cancer when compared to those taking TNF inhibitors, according to the researchers.

All of these findings are now included in the boxed warning section of the updated Xeljanz label. Existing approvals for the drug for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and juvenile idiopathic arthritis are now being pushed behind Tumor Necrosis Factor (TNF) blockers as first-line treatment.

Although the red flags came from the Xeljanz study, the FDA clearly demonstrated that it considers the risks to be a classwide issue for oral JAK inhibitors by requiring similar label updates for Rinvoq and Olumiant.

Even before the recent changes, the three JAK inhibitors had boxed warnings about similar risk factors, but not in comparison to other TNF drugs.

While the FDA has approved the labels for Xeljanz and Rinvoq, there are still significant unknowns. All three JAK inhibitors are still awaiting FDA approval in the large atopic dermatitis indication.

Furthermore, Pfizer’s new JAK inhibitor Cibinqo, which is already approved in the UK, and Bristol Myers Squibb’s Tyrosine Kinase 2 (TYK2) inhibitor deucravacitinib are awaiting FDA approval to enter the US market. TYK2 belongs to the JAK family.

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