February 2021 FDA Warning: Xeljanz Increased Risks for Serious Heart-related Problems and Cancers
During the past few years, there have been some Xeljanz drug safety alerts issued by the FDA based on a post-marketing safety clinical trial ordered by the FDA when it first approved Xeljanz (tofacitinib) in 2012. That clinical trial often goes by its short name, ORAL Surveillance, instead of its full title, "Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis".
For some commentary on this Xeljanz safety trial, which started in March 2104 and was completed in July 2020, we go to this February 16, 2021, Healio Rheumatology article, "'We need to see the data': FDA's Xeljanz safety warning stirs concerns for JAK inhibitors":
[D]espite this trial wrapping in July 2020, its full results, beyond the co-primary endpoints — including secondary endpoints such as pulmonary embolism and mortality as well as efficacy data — remain unavailable. Only the topline results have been released, and only through alerts and press releases from the FDA and Pfizer.
This has left many experts anxious to dig into the full data, which could hold drastic consequences not only for Xeljanz, but also for [Janus kinase (JAK) inhibitors] as a class. Until then, they said, it’s difficult to forecast what impact these results will have.
In our recent post, "Xeljanz FDA Drug Safety Communication in February 2021 Puts Heightened Scrutiny on Pfizer", we touched upon the two latest Xeljanz safety issues, Xeljanz causing heart problems and Xeljanz causing cancer. But there is still a lot that we do not know, yet, about how significant this new drug safety issue, or will be, for Xeljanz -- and Pfizer, the pharmaceutical company responsible for Xeljanz.
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The February 2021 Healio Rheumatology article referenced above helps us a bit on that front:
Pfizer, via a press release, announced the co-primary endpoint results of the completed study in January. Those endpoints — noninferiority with [Xeljanz (tofacitinib)] compared with TNF inhibitors related to major adverse cardiovascular events and malignancies excluding non-melanoma skin cancer — were not met, the company said. In addition, based on the prespecified secondary comparisons, there was no evidence of a difference in the primary endpoints between the two [Xeljanz (tofacitinib)] treatment groups.
According to the Pfizer release, the primary analyses included 135 participants with major adverse cardiovascular events and 164 subjects with malignancies. For [Xeljanz (tofacitinib)], the most frequently reported cardiac event was myocardial infarction, while the most frequently reported malignancy was lung cancer.
This article goes on to point out that despite the lack of data from this Xeljanz safety trial completed in July 2020, the results which have been available to date are concerning for rheumatologists:
[Stanley Cohen, MD, clinical professor in the department of internal medicine at the University of Texas Southwestern Medical School, and medical codirector of the Metroplex Clinical Research Center, told Healio Rheumatology] the fact that ORAL Surveillance was a head-to-head trial suggests there is “certainly a signal” for major cardiovascular events and cancer with [Xeljanz (tofacitinib)].
“I do think these results are serious,” Cohen said. “I think it’s something we have to look at critically, and again, with just the topline — what can you say? We need to look at all the data and better understand the data.
Lastly, the February 2021 FDA safety alert about Xeljanz having increased risks for serious heart-related problems and cancers raises the issue of whether all JAK inhibitors share these side effect risks:
According to Cohen, Pfizer’s results with Xeljanz indicate that other companies that produce JAK inhibitors should likely go back and examine their clinical trial programs, selecting out those patients with the same risk factors to see if there was any imbalance in MACE or malignancies.
Besides Xeljanz, there are two other JAK inhibitors approved by the FDA:
- Olumiant (baricitinib) from Eli Lilly & Co.; and,
- Rinvoq (upadacitinib) from AbbVie.
As such, besides just watching for more data from the Xeljanz safety trial showing an increased risk of serious heart-related problems and cancer associated with Xeljanz, we will look for any related developments concerning Olumiant and Rinvoq.
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