JAK Inhibitors Xeljanz, Olumiant, and Rinvoq Get Drug Label Changes and Drug Use Limitations in September 2021


(Posted by Tom Lamb at Drug Injury Watch)


On September 1, 2021, the FDA released this alerting news about the association of Xeljanz use with adverse events involving blood clots and death: The increased risk of blood clots and death has been linked to the lower dose of Xeljanz as well as the higher dose of Xeljanz; put otherwise, both FDA-approved doses of Xeljanz are linked to these “side effects”, or adverse drug reactions.

This September 2021 document, “FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions“, begins with the following new information:

Based on a completed U.S. Food and Drug Administration (FDA) review of a large randomized safety clinical trial, we have concluded there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with the arthritis and ulcerative colitis medicines Xeljanz and Xeljanz XR (tofacitinib). This trial compared Xeljanz with another type of medicine used to treat arthritis called tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis. The trial’s final results also showed an increased risk of blood clots and death with the lower dose of Xeljanz. A prior DSC based upon earlier results from this trial, reported an increased risk of blood clots and death only seen at the higher dose.  [Emphasis added.]

And here is what the FDA doing “new”, now, in September 2021 — after some earlier FDA regulatory actions pertaining to Xeljanz over the past couple of years:

We are requiring revisions to the Boxed Warning, FDA’s most prominent warning, for Xeljanz/Xeljanz XR, Olumiant, and Rinvoq to include information about the risks of serious heart-related events, cancer, blood clots, and death. Recommendations for health care professionals will include consideration of the benefits and risks for the individual patient prior to initiating or continuing therapy. In addition, to ensure the benefits of these three medicines outweigh the risks in patients who receive them, we are limiting all approved uses to certain patients who have not responded or cannot tolerate one or more TNF blockers….

In more detail, from the Data Summary section of the above-referenced September 2021 document, here are the most recent FDA findings as regards various Xeljanz side effects:

There was an increased risk of death, MACE, malignancies, and thrombosis associated with both regimens of Xeljanz. The data showed evidence of a dose-dependent increased risk for [major adverse cardiovascular events (MACE) — defined as cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke], all-cause mortality, and thrombosis at both doses of Xeljanz when compared to treatment with [tumor necrosis factor (TNF) blockers]. Additionally, the data showed evidence of a non-dose-dependent increased risk for malignancy excluding [nonmelanoma skin cancer (NMSC)] at both doses of Xeljanz when compared to TNF blockers. Lymphomas and lung cancers were observed at a higher rate in patients treated at both doses of Xeljanz compared to those treated with TNF blockers. In particular, a higher rate of lung cancers was observed in current or past smokers treated with Xeljanz. Current or past smokers had an additional increased risk of overall cancers.

Other JAK inhibitors [specifically, Olumiant (baricitinib) and Rinvoq (upadacitinib)] have not been studied in similar large safety clinical trials, so the risk with these medicines has not been evaluated. However, since [Olumiant and Rinvoq] share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the safety clinical trial with Xeljanz.

However, this September 2021 FDA regulatory action regarding Xeljanz is not altogether unexpected, as can be seen by these five Drug Injury Watch articles about Xeljanz drug safety developments which we wrote earlier this year:

  1. Possible FDA Advisory Committee Meeting for Xeljanz, Rinvoq, and Other Janus Kinase (JAK) Inhibitors  (July 6, 2021)
  2. Xeljanz and Other JAK Inhibitors: Drug Safety Concerns Indicated by Recent FDA Actions  (April 15, 2021)
  3. Possible Ramifications of Recent FDA Alert About Xeljanz Heart Problems and Xeljanz-related Cancers  (March 23, 2021)
  4. Xeljanz Has A New Drug Safety Issue, We Just Don’t Know How Significant It Is, Yet  (February 17, 2021)
  5. Xeljanz FDA Drug Safety Communication in February 2021 Puts Heightened Scrutiny on Pfizer  (February 11, 2021)

Our law firm is investigating Xeljanz lawsuits filed against Pfizer, the pharmaceutical company responsible for Xeljanz, for cases of Xeljanz causing heart problems such as heart attacks and strokes as well as Xeljanz causing cancers.

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