Other JAK Inhibitors May Be Negatively Affected by Xeljanz Study Results, Too
Written by: Lauren Schwab, Legal Assistant
Law Offices of Thomas J. Lamb, P.A.
On February 5, 2021, we reported on a potential upcoming Xeljanz recall following a Drug Safety Communication from the U.S. Food and Drug Administration (FDA) regarding new evidence about Xeljanz adverse events in our article, "Will There Be a Xeljanz Recall in the Future?". We will now provide you with a more in-depth look into the results of the Xeljanz safety trial, or Xeljanz study, that prompted the February 2021 FDA Drug Safety Communication about Xeljanz.
Xeljanz Study Results
On Wednesday, January 27, 2021, Pfizer announced the results from the FDA-mandated Xeljanz safety trial. This Xeljanz study was composed of a randomized group of 4,362 patients who all had at least one cardiovascular risk factor and were taking either a 5 or 10 mg/day dosage of Xeljanz or a tumor necrosis factor (TNF) inhibitor. The study found patients taking Xeljanz showed significantly higher rates of adjudicated malignancies when compared with patients taking TNF inhibitors. Similarly, those taking Xeljanz saw significantly higher rates of major adverse cardiovascular events (MACE) compared to TNF inhibitors.
According to January 27, 2021 article, "JAK Inhibitor Mises Endpoint in Safety Study. Now What?":
Adverse events were pooled for the two [Xeljanz (tofacitinib)] doses for evaluating the primary endpoints. Incidence rates for MACE were slightly higher with the 10-mg versus 5-mg dose (10.5 vs 9.1 per 1,000 person-years); rates of malignancies did not differ between dosages. Following a signal for increased risk of pulmonary embolism and mortality at the higher dose, patients in the 10-mg arm were moved to the 5-mg dose in early 2019.
Cancer and MACE safety signals had been noted in the drug's clinical trials and later postmarketing reports, leading to cautions on tofacitinib's label, including boxed warning about increased mortality, thrombosis, and lymphoma and other malignancies.
While the complete analysis of the Xeljanz study conducted by Pfizer has not yet been published, the company reports they are working with the FDA to review the Xeljanz safety trial results as they become available. It is expected the results of the study will yield further data on Xeljanz and pulmonary embolism, mortality, and comparative effectiveness.
Xeljanz is classified as a JAK inhibitor, which works by blocking Janus kinases (JAKs), which is an enzyme that regulates immune cells. This allows for Xeljanz to fight inflammatory diseases such as rheumatoid arthritis and ulcerative colitis. Recent studies like the Pfizer report on Xeljanz look into the concern JAK inhibitors may impair the body's ability to fight off dangerous microbes or cancer.
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How Xeljanz Fares Against TNF Inhibitors and Other JAK Inhibitors
According to January 27, 2021 article, "Safety finding weighs on Pfizer's inflammation drug, and could spell trouble for others", the results of the Xeljanz study could have impacts on other JAK inhibitors, and even TNF inhibitors:
Results show that among Xeljanz-treated patients, 98, or 3.37%, had a major cardiovascular event sometime between when they started treatment to 60 days after they stopped. In the TNF group, 37, or 2.55%, experienced such an event. Malignancies, excluding non-melanoma skin cancer, were seen in 122, or 4.19%, of patients given Xeljanz and 42, or 2.89%, of patients given a TNF inhibitor. With regard to Xeljanz, Pfizer said heart attack and lung cancer were the most frequently reported major cardiovascular events and malignancies, again excluding non-melanoma skin cancer.
Other JAK inhibitors since Xeljanz have also been approved for use by the FDA, though some of them also carry Black Box Warnings about infections, thrombosis, and cancer risk.
According to January 27, 2021 article, "Pfizer's big blockbuster Xeljanz flunks its post-marketing safety study, renewing harsh questions for JAK class", Xeljanz may not fare well against TNF inhibitors:
And on Wednesday, Pfizer announced that the six-year study had failed. Across 4,362 patients, those who received either a low or high dose of Xeljanz experienced more major cardiovascular events — such as stroke and heart attack — than those on Humira or Enbrel. They also had higher rates of cancer, with Pfizer failing to hit non-inferiority on both primary endpoints.
However, overall it seems we do not have enough data to come to a conclusion about a possible Xeljanz recall or other JAK inhibitors recalls. According to the same January 27, 2021 article, "Pfizer's big blockbuster Xeljanz flunks its post-marketing safety study, renewing harsh questions for JAK class":
It’s also not yet clear how the new findings will impact JAK inhibitors more broadly. In a note to investors, RBC’s Brian Abrahams said physicians already take safety issues into account when considering JAK inhibitors, but that the new data could make the FDA “even more risk-averse on labeling for the class going forward.” That could impact Incyte as they await the FDA’s decision on a topical formulation for Jakafi, one of the only JAK inhibitors that does not yet have a black box warning.
Current FDA Recommendations
Although the FDA has released a safety alert warning patients about the associated risks of Xeljanz, physicians are currently still recommended to continue to follow the recommendations listed in the drug's prescribing information. Patients are advised not to discontinue Xeljanz use without first consulting their physician.
According to February 2, 2021 article, "FDA warns of increased risk for heart-related issues, cancer linked to Xeljanz", Pfizer is committed to a continued review of results from the recent Xeljanz study:
“Providing information on the safe and effective use of our medicines is imperative,” Tamas Koncz, MD, PhD, chief medical officer for Inflammation and Immunology at Pfizer, said in a company release. “We believe that extensive additional analyses of these study data, and communicating them as soon as possible, will further clarify the benefit and risk profile of tofacitinib to help inform medical decision-making and patient care.”
The FDA is currently recommending health care providers report any adverse events related to Xeljanz to the FDA's MedWatch Safety Information and Adverse Events Reporting Program.
Be assured that we will continue to follow this latest Xeljanz drug safety issue as well as watch for possible further FDA regulatory actions, including a possible Xeljanz recall.
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