Drug Injury Watch

Ozempic Side Effects: Gallbladder Diseases, Thyroid Cancer, And Suicidal Thoughts

Diabetes and Weight-Loss Drug Ozempic Getting Scrutiny From European Drug Safety Regulator EMA

 

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***See also: Ozempic Severe Gastric Side Effects Include Stomach Paralysis, Gastroparesis, And Intestinal Blockages

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(Posted by Tom Lamb at Drug Injury Watch)

 

The popular diabetes and weight-loss drug Ozempic (semaglutide) has been linked to gallbladder diseases which may require gallbladder removal surgery. Other Ozempic side effects being investigated by the European Medicines Agency (EMA) are thyroid cancer and suicidal thoughts.

Starting with the gallbladder disease Ozempic side effects, we previously posted this Drug Injury Watch article, "Ozempic Gallbladder Injury Case Factors: When was the Ozempic Prescribed and For How Long?", which covered the March 2022 Ozempic label change that added warnings about the risks of gallbladder diseases.

Turning next to the possible association between Ozempic and thyroid cancer, we refer you to a June 22, 2023, Reuters news report, "Novo Nordisk says EMA raised safety signal on drugs including semaglutide", which includes this information:

A thyroid cancer safety signal was raised by the EU's drugs watchdog last month over several Novo Nordisk products including semaglutide, which is used in popular diabetes and obesity medicines Ozempic and Wegovy.

The European Medicines Agency (EMA) raised the safety signal, which is a way to monitor potential adverse events from the use of approved drugs, Novo Nordisk said. Such a signal from the EMA does not mean that the medicine is the cause of any reported adverse events.

"Novo Nordisk is aware of the signal and the request by EMA and will deliver a thorough assessment of all relevant data to elucidate this topic," Lars Otto Andersen-Lange, media relations director at Novo Nordisk, told Reuters....

Both EMA and its U.S. equivalent, the FDA, mention on Wegovy's label that semaglutide causes thyroid tumours in rodents but say the effects on humans are unknown. The FDA advises against taking Wegovy if the patient has a family history of thyroid cancer.

We point out that the current Ozempic Prescribing Information document (Revised: 03/2022) also has a warning about a risk of thyroid C-cell tumors.

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Lastly, we take a look at the more recently announced EMA investigation into Ozempic and suicidal thoughts. We begin with this July 10, 2023, Reuters news report, "E.U. investigates Ozempic and weight-loss drug Saxenda after reports of suicidal thoughts", from which we get the following:

The European Medicines Agency is investigating Novo Nordisk’s diabetes drug Ozempic and weight-loss treatment Saxenda after Iceland’s health regulator flagged three cases of patients thinking about suicide or self-harm....

The EMA’s investigation centers on medicines that contain either semaglutide or liraglutide. Novo’s obesity treatment Wegovy, for which demand has surged in the United States, contains semaglutide.

The review was announced weeks after the regulator raised a thyroid cancer safety signal, a means to monitor potentially adverse effects, on several of Novo’s products containing semaglutide.

Suicidal thoughts are not listed as a side effect in the E.U. product information for either drug.

In the United States, however, prescribing instructions for Wegovy recommend that patients are monitored for suicidal thoughts or behavior.

According to the U.S. Food and Drug Administration Adverse Event Reporting System Public Dashboard, there have been at least 60 reports of suicidal ideation since 2018 from patients on semaglutide or their health care providers.

For additional details we point out "Updated: European regulators investigating 150 reports of self-injury, suicide risk in patients taking Novo Nordisk meds for weight loss", which includes this July 2023 reporting by Endpoints News:

The European Medicines Agency is looking into about 150 reports of “possible cases of self-injury and suicidal thoughts” for weight loss patients who used Novo Nordisk’s semaglutide or liraglutide medicines.

The first three case reports were flagged by member agency Icelandic Medicines Agency, unveiled on Monday. The EMA’s safety committee, the Pharmacovigilance Risk Assessment Committee (PRAC), is now investigating.

“The case reports included two cases of suicidal thoughts, one following the use of Saxenda and one after Ozempic. One additional case reported thoughts of self-injury with Saxenda,” the EMA said via email to Endpoints News, before issuing an updated statement today.

The EMA said its review of Ozempic, Saxenda and Wegovy began on July 3 and has now been extended to include other GLP-1 receptor agonists. This review is expected to conclude in November 2023, the regulator said in a statement.

The EMA updated statement referenced above is "EMA statement on ongoing review of GLP-1 receptor agonists", issued July 11, 2023, and here is its introduction to this latest Ozempic drug safety issue:

EMA’s safety committee, the PRAC, is reviewing data on the risk of suicidal thoughts and thoughts of self-harm with medicines known as GLP-1 receptor agonists, including Ozempic (semaglutide), Saxenda (liraglutide) and Wegovy (semaglutide). These medicines are used for weight loss and for treating type 2 diabetes.

At the present time, our law firm is reviewing Ozempic drug injury cases involving gallbladder diseases that lead to the need for gallbladder removal surgery. If we can be of assistance to you or someone you know, we encourage you to submit a Case Evaluation Form online. Or, if you prefer, call our toll-free number, (800) 426-9535,

As regards the possible Ozempic side effects of thyroid cancer and suicidal thoughts or self-injury, we will continue to monitor the two ongoing EMA investigations discussed in this article for further findings as regards these Ozempic drug safety issues.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (Website content is written by Tom Lamb)

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Off-Topic Alert: Breast Implants Lymphoma Cancer ALCL Case Numbers Increasing Rapidly in the US

New Estimates Reported in July 2022 Medical Journal Article Reveal BIA-ALCL is Diagnosed More Often as Time Goes On

 

(Posted by Tom Lamb at Drug Injury Watch)

 

A research letter published July 21, 2022 in JAMA Oncology, "Incidence of Anaplastic Large-Cell Lymphoma of the Breast in the US, 2000 to 2018" (subscription required), presented some new research about current population-based estimates of the incidence of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in the US, and the findings are rather alarming.

From this recent news report, "ALCL Increasing Rapidly in US Women as Breast Implants Rise", about that recent medical journal article:

The team, led by Connor Kinslow, MD, Columbia University, New York City, looked at the age-adjusted annual incidence rate of ALCL and found that it increased over time.

The incidence was 3.2 per 100 million persons per year from 2000-2005, then increased to 4.4 per 100 million persons per year from 2006-2011, and then tripled to an incidence of 14.5 per 100 million persons per year from 2012-2018.

"Similar rates and trends were observed when including cases of T-cell lymphoma not otherwise specified," the authors note, at a rate of 19.6 per million persons per year in [the period] 2012 to 2018.

These current incidence estimates are much higher than the previous estimate of 3 per 100 million persons per year quoted by the Food and Drug Administration (FDA), which had been based on data from the Surveillance, Epidemiology and End Results (SEER) data base from 2001-2007, the authors note.

"These trends are concerning, as the use of textured implants increased more than 5-fold from 2.3% to 13% of augmentation procedures between 2011 and 2015, despite a safety communication from the FDA in 2011," they comment.

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For some expert commentary on these new BIA-ALCL findings released in July 2022, we turn to this MedPage Today article, "Breast Implant-Related Lymphoma More Common Than Reported", by medical reporter Charles Bankhead:

Though "certainly concerning," the findings came from a study period that ended in 2018, the year before the FDA and regulatory agencies in other countries issued a recall of Allergan textured implants, the ones most closely associated with ALCL, noted Deanna J. Attai, MD, of the Jonsson Comprehensive Cancer Center at UCLA in Los Angeles.

"As all national databases lag by several years, it is likely too soon to determine if the incidence of ALCL has decreased as a result of the recall," Attai, who was not involved in the analysis, told MedPage Today via email. "However, as the FDA has not recommended removal of textured implants in the absence of symptoms, women with textured implants should be aware that prior estimates of the risk of ALCL are lower than what is currently being reported."

Our law firm has been representing several women diagnosed with anaplastic large cell lymphoma that has been linked to their textured breast implants. As such, we are monitoring the BIA-ALCL situation and will present add significant developments going forward on the Breast Implants Lymphoma Cancer page on our law firm website, where we offer a free case evaluation if you or someone you know has been diagnosed with BIA-ALCL.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

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Multiple Sclerosis (MS) Drugs Gilenya and Ocrevus Associated With a Higher Likelihood of Melanoma Skin Cancer

Other MS Treatments Such as Lemtrada and Mayzent May Have an Increased Risk of Basal Cell Carcinoma and Squamous Cell Carcinoma

 

(Posted by Tom Lamb at Drug Injury Watch)

 

An analysis of skin cancers reported to the FDA Adverse Event Reporting System (FAERS) has revealed the need for close skin cancer monitoring in patients receiving certain multiple sclerosis (MS) therapies, including the drugs Gilenya, Lemtrada, Mayzent, and Ocrevus. In particular, the findings showed the MS drugs Gilenya and Ocrevus linked to melanoma, with Gilenya linked to squamous cell carcinoma and basal cell carcinoma, also.

These findings come from a research study reported in this recent article, "S1P receptor modulators in Multiple Sclerosis: Detecting a potential skin cancer safety signal", published by the medical journal Multiple Sclerosis and Related Disorders.

From the Abstract for this March 2022 medical journal article, in its Introduction section, we get the following:

[Sphingosine 1-phosphate (S1P)] receptor modulators are oral Disease-Modifying Therapies (DMTs) for Multiple Sclerosis, which were associated with cases of basal cell carcinoma in clinical trials. This study aims at investigating in a real-world adverse event reporting system whether S1P receptor modulators increase the risk of skin cancer reporting, compared to other DMTs.

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For more details, from the full-text Conclusion part of this new medical research article:

The present study detected a potential safety signal for the S1P receptor modulators [Gilenya (fingolimod)] and [Mayzent (siponimod)] for basal cell carcinomas. [Gilenya (fingolimod)] had also an increased signal of disproportionate reporting for melanoma and squamous cell carcinoma. [Lemtrada (alemtuzumab)] presented also a signal for all three types of skin cancer, while [Ocrevus (ocrelizumab)] presented a potential safety signal for melanoma.... These findings -- especially the potential signals for melanoma -- need to be further evaluated, including more substantial evidence from other real-world prospective trials. Based on the current evidence and taken the rapid development of new orally administered S1P receptor modulators, such as Ozanimod and Ponesimod into consideration, monitoring measures such as skin examination at baseline to screen for precancerous skin lesions or additional risk factors, regular dermatologic examinations, and patient's education for regular self-skin controls seem indicated for MS patients under treatment with S1P receptor modulators.

For some explanation of this MS drugs adverse reactions research study, we refer you to a Multiple Sclerosis News Today article, "More Skin Cancer Reported to FDA From Patients on Certain Oral DMTs".  This news report points out these two important facts:

1. The findings showed the MS drugs Gilenya and Ocrevus linked to melanoma skin cancer: and,
2. The findings showed Gilenya linked to squamous cell carcinoma and basal cell carcinoma, also.

We will continue to monitor the safety profile of Gilenya and Ocrevus, as well as Lemtrada and Mayzent, with a focus on the possible increased risks of these three skin cancers: melanoma; squamous cell carcinoma; and, basal cell carcinoma.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

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JAK Inhibitors Safety Review by European Drug Regulator EMA Announced in February 2022

Xeljanz, Rinvoq, and Olumiant as Treatments for Inflammatory Disorders Have Been Under Scrutiny by FDA in the US

 

(Posted by Tom Lamb at Drug Injury Watch)

 

In December 2021 there was a notable JAK inhibitors drug class safety development in the US, with Xeljanz, Olumiant, and Rinvoq getting revised drug labels with more side effects warnings and more drug use restrictions. These December 2021 JAK inhibitors label changes were “new” but anticipated because back in September 2021 the FDA announced that it was requiring revisions to the “Black-Box” warnings already on the drug labels for Xeljanz, Olumiant, and Rinvoq “to include more information about the risks of serious heart-related events, cancer, blood clots, and death.”

Now the issue of JAK inhibitors drug class safety is coming up in Europe, as indicated by this European Medicines Agency (EMA) February 11, 2022, news item, "EMA starts safety review of Janus kinase inhibitors for inflammatory disorders".

Consistent with the December 2021 JAK inhibitors label changes mandated by the FDA here in the US, Xeljanz, Rinvoq, and Olumiant as treatments for inflammatory disorders are the subject of this JAK inhibitors safety review announced by the EMA in February 2022.

From the above-referenced EMA news item:

The review was prompted by the final results from a clinical trial (study A3921133) of the JAK inhibitor Xeljanz (tofacitinib). The results showed that patients taking Xeljanz for rheumatoid arthritis and who were at risk of heart disease were more likely to experience a major cardiovascular problem (such as heart attack, stroke or death due to cardiovascular disease) and had a higher risk of developing cancer than those treated with medicines belonging to the class of TNF-alpha inhibitors....

In addition, preliminary findings from an observational study involving another JAK inhibitor, Olumiant (baricitinib), also suggest an increased risk of major cardiovascular problems and VTE in patients with rheumatoid arthritis treated with Olumiant compared with those treated with TNF-alpha inhibitors.

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During this past 12 months, to the day, we have written these 12 earlier Drug Injury Watch articles which are relevant to Xeljanz, Rinvoq, and Olumiant, given that they are about JAK inhibitors drug class safety and JAK inhibitors label changes:

1. Xeljanz FDA Drug Safety Communication in February 2021 Puts Heightened Scrutiny on Pfizer (February 11, 2021)
2. Xeljanz Has A New Drug Safety Issue, We Just Don't Know How Significant It Is, Yet (February 17, 2021)
3. Possible Ramifications of Recent FDA Alert About Xeljanz Heart Problems and Xeljanz-related Cancers (March 23, 2021)
4. Xeljanz and Other JAK Inhibitors: Drug Safety Concerns Indicated by Recent FDA Actions (April 15, 2021)
5. Possible FDA Advisory Committee Meeting for Xeljanz, Rinvoq, and Other Janus Kinase (JAK) Inhibitors (July 6, 2021)
6. Xeljanz: FDA Warnings Updated: There are Higher Rates of Blood Clots and Deaths for Both Doses of Xeljanz, Now (September 1, 2021)
7. Xeljanz: Drug-induced Peripheral Neuropathy as Possible Xeljanz Side Effect in 2 RA Patients (September 29, 2021)
8. Xeljanz Risks of Cardiovascular Events, as well as Cancers, Cause More Xeljanz Use Limitations (October 12, 2021)
9. Eli Lilly Attempts to Distance Olumiant From the Ominous JAK Inhibitors Drug Class Safety Issues Flagged by FDA (November 29, 2021)
10. December 2021 JAK Inhibitors Drug Class Label Changes: More Warnings and Use Restrictions (December 9, 2021)
11. Xeljanz Link to Cancers, Heart Attacks, Strokes, and Cardiovascular Deaths is Confirmed by Health Canada in January 2022 (January 14, 2022)
12. Xeljanz Safety Study Final Data Details the Increased Risks of Cancers and Major Adverse Cardiovascular Events (January 31, 2022)

Our law firm is investigating possible drug injury lawsuits involving Xeljanz, Rinvoq, and Olumiant for patients who have suffered serious side effects or adverse drug reactions. Feel free to contact us if you or someone you know might have a Xeljanz, Rinvoq, or Olumiant drug injury case. 

To learn more, you can visit the Xeljanz | Rinvoq | Olumiant Side Effects page on our Drug Injury Law website.

And, of course, we will continue to watch for future developments related to JAK inhibitors drug class safety and JAK inhibitors label changes, as we have done during the past 12 months.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

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Xeljanz Safety Study Final Data Details the Increased Risks of Cancers and Major Adverse Cardiovascular Events

January 2022 Medical Journal Article Presents Full Set of Findings for the Xeljanz "ORAL Surveillance" Trial Which Started in 2014

 

(Posted by Tom Lamb at Drug Injury Watch)

 

One year ago Pfizer released some preliminary results from the so-called "ORAL Surveillance" trial ordered by the FDA when Xeljanz (tofacitinib) was first approved for rheumatoid arthritis in 2012, and which started in 2014. In part, those early Xeljanz safety findings involved data about increased risks of cancer and heart-related side effects, which the FDA also considers applicable to Rinvoq and Olumiant, other medicines in the JAK inhibitors drug class.

In the January 27, 2022 edition of the New England Journal of Medicine (NEJM), there was this article, "Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis", which reported the final results of the ORAL Surveillance trial. In that same January 2022 NEJM edition there was an editorial piece, "Risks and benefits of Janus kinase inhibitors in rheumatoid arthritis -- past, present, and future", that discussed the significance of those Xeljanz safety findings.

The final results from this ORAL Surveillance Xeljanz safety study were examined in this January 26, 2022 article, "Trial Data Confirm Heightened Risks With JAK Inhibitor", by medical news reporter John Gever for MedPage Today.

That January 2022 MedPage Today news report provides a "snapshot" of the current safety profile for Xeljanz as regards cancer and heart-related side effects:

It's official: full data from a randomized trial evaluating safety of the oral JAK inhibitor tofacitinib (Xeljanz), approved for treating rheumatoid arthritis and related disorders as well as ulcerative colitis, are now published -- and they are not good.

Patients assigned to [Xeljanz] developed major adverse cardiovascular events (MACE) at a rate of 3.4% and new cancers were seen in 4.2% during a median 4 years of follow-up; for those treated with either adalimumab (Humira) or etanercept (Enbrel), the corresponding rates were 2.5% and 2.99%, respectively, according to a report in the New England Journal of Medicine.

This worked out to hazard ratios of 1.33 for MACE (95% CI 0.91-1.94) and 1.48 for incident cancers (95% CI 1.04-2.09), reported investigators led by Steven Ytterberg, MD, of the Mayo Clinic in Rochester, Minnesota....

In their paper, Ytterberg and colleagues stuck to reporting the trial's results, offering no advice to patients or clinicians on how to interpret them.

That was left to editorialist Jasvinder Singh, MBBS, MPH, of the University of Alabama at Birmingham. He noted that the drug -- along with its chemical cousins baricitinib (Olumiant) and upadacitinib (Rinvoq) -- already come with boxed warnings about the risk, which were stiffened again just last month. The agency also tightened eligibility criteria for [Xeljanz] and [Rinvoq] to allow the drugs only in patients failing on TNF inhibitors; previously, patients could receive them after failing nonbiologic drugs.

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Taking into account the above new information about Xeljanz safety findings, to date some of the serious side effects and adverse drug events that have been associated with Xeljanz, Rinvoq, and Olumiant are:

Heart Attacks
Myocardial Infarction (MI)
Strokes — Ischemic / due to a blood clot
Deep Vein Thrombosis (DVT)
Pulmonary Embolism (PE)
Arterial Thrombosis
Lymphoma
Lung Cancer
Other Cancers
Death

Our law firm is investigating possible Xeljanz, Rinvoq, and Olumiant lawsuits for patients who have suffered any of these serious side effects or adverse drug reactions. We would like to help you or someone you know with a Xeljanz, Rinvoq, or Olumiant drug injury case. Please feel free to contact us, at your convenience.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

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Xeljanz Link to Cancers, Heart Attacks, Strokes, and Cardiovascular Deaths is Confirmed by Health Canada in January 2022

Xeljanz Safety Alert for People Who Are (1) Older, (2) Current / Past Smokers, or (3) With Cardiovascular or Cancer Risk Factors

 

(Posted by Tom Lamb at Drug Injury Watch)

 

The drug regulatory agency Health Canada issued this news release item on January 12, 2022, which points out the results of their recent examination of some serious side effects associated with Xeljanz: "Advisory - Health Canada safety review finds link between the use of Xeljanz and Xeljanz XR (tofacitinib) and increased risk of serious heart-related issues and cancer". This January 2022 Health Canada news release is the latest development concerning Xeljanz drug safety, Xeljanz side effects, and Xeljanz warnings, topics which we began reporting on back in early 2019, starting with this article, "Xeljanz Recommended Dosage For Ulcerative Colitis Patients May Increase Risk Of Pulmonary Embolism".

This excerpt from the January 2022 Health Canada Xeljanz Advisory document provides an overview of the Xeljanz drug safety issue, and how the Xeljanz side effects risks may also apply to Olumiant and Rinvoq:

Health Canada completed a safety review that confirmed a link between the use of Xeljanz/Xeljanz XR and the increased risks of serious heart-related problems and cancer, especially in older patients, patients who are current or past smokers, and patients with cardiovascular or cancer risk factors. Health Canada's review also found that all patients treated with Xeljanz 10 mg twice daily had a higher risk of death, blood clots and serious infections, compared to patients treated with Xeljanz 5 mg twice daily or tumour necrosis factor inhibitors (TNFi)....

Health Canada has also initiated a new safety review of the potential risks of serious heart-related problems, cancer and blood clots with two other drugs of the same class as Xeljanz/Xeljanz XR (i.e. Olumiant and Rinvoq) that work similarly for the treatment of similar diseases.

As background, Xeljanz (tofacitinib), Olumiant (baricitinib), Rinvoq (upadacitinib) are Janus kinase (JAK) inhibitors. Xeljanz is a Pfizer drug, Olumiant is an Eli Lilly drug, and Rinvoq is an AbbVie drug.

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The Health Canada Xeljanz Advisory gives some more detailed information in a section intended for healthcare professionals but, no doubt, of interest to patients using Xeljanz -- as well as Olumiant or Rinvoq, perhaps:

• Inform patients that Xeljanz/Xeljanz XR may increase their risk of major adverse cardiovascular events including non-fatal myocardial infarction. Instruct all patients, especially geriatric patients, current or past smokers, or patients with other cardiovascular risk factors, to be alert for signs and symptoms of cardiovascular events.
• Inform patients that Xeljanz/Xeljanz XR may increase their risk of certain cancers, and that lung cancer, lymphoma and other cancers have been observed in patients taking Xeljanz. Instruct patients to inform their healthcare provider if they have ever had any type of cancer.

Our law firm is investigating possible drug injury lawsuits for patients who used Xeljanz, Olumiant, or Rinvoq and then suffered one of the serious side effects associated with these JAK inhibitors drugs. In particular, heart problems such as heart attacks, strokes, pulmonary embolism (PE), and deep vein thrombosis (DVT), as well as cancers such as lymphoma and lung cancer.

We will continue to watch for further developments concerning Xeljanz drug safety, Xeljanz side effects, and Xeljanz warnings in the drug regulatory sector.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

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December 2021 JAK Inhibitors Drug Class Label Changes: More Warnings and Use Restrictions

Risks of Cancers, Blood Clots, Heart Problems, and Deaths Associated with Xeljanz, Olumiant, and Rinvoq

 

(Posted by Tom Lamb at Drug Injury Watch)

 

As background, in September 2021 the FDA announced that it was requiring revisions to the "Black-Box" warnings already on the drug labels for Xeljanz, Olumiant, and Rinvoq "to include more information about the risks of serious heart-related events, cancer, blood clots, and death." (See: "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")

Before going into some commentary found in news reports about the effects of this December 2021 JAK inhibitors drug class safety development, here are links to the "new" drug label for Xeljanz, Olumiant, and Rinvoq:

• Current Prescribing Information for Xeljanz (Revised: 12/2021)
• Current Prescribing Information for Olumiant (Revised: 12/2021)
• Current Prescribing Information for Rinvoq (Revised: 12/2021)

Xeljanz is a Pfizer drug, Rinvoq is an AbbVie drug, and Olumiant is an Eli Lilly drug. As we wrote about in this recent article, "Eli Lilly Attempts to Distance Olumiant From the Ominous JAK Inhibitors Drug Class Safety Issues Flagged by FDA", the pharmaceutical companies AbbieVie and Eli Lilly have attempted to distinguish the safety profile of their respective JAK inhibitors drug product from the various adverse drug reactions that have been observed in the Xeljanz clinical trial that have driven the FDA regulatory actions driving these December drug label changes.

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One pharmaceutical industry commentator thinks that AbbVie may have an advantage in "market share" going forward as regards the three JAK inhibitors drugs approved for the treatment of rheumatoid arthritis, given some details of the new drug label for Rinvoq. From this December 6, 2021, Fierce Pharma news report, "AbbVie's Rinvoq, Pfizer's Xeljanz and Lilly's Olumiant slapped with new FDA warnings amid JAK safety crackdown", we get the following:

Rinvoq appears to have got what [SVB Leerink analyst Geoffrey Porges] called “milder language” on the risks. The new Rinvoq boxed warning specifies that the higher rates of the safety problems over TNF blockers are observed in another JAK inhibitor. What’s more, there were no restrictions on how long a patient can take Rinvoq.

The somewhat better-than-expected wording will “make a modest difference” only to new physicians or those who aren’t familiar with JAKs, he said in a Monday note.

Nevertheless, Porges believes Rinvoq is in a better position than the other two JAK inhibitors “given the strength of the data and AbbVie’s well-entrenched position in immunology.” Plus, no other drug regulators outside the U.S. have posted similar restrictions, he noted.

For a similar viewpoint, we move to this December 6, 2021, Evaluate Vantage piece, "New label warnings raise hopes for Jak safety closure", which also indicates that this December 2021 JAK inhibitors drug class FDA regulatory action could have been worse:

The full fallout from the FDA’s safety review of the Jak inhibitors remains unknown, amid concerns about moves to curb these drugs’ use drastically. But two label updates that emerged late Friday are raising hopes that draconian measures are off the table. Abbvie and Pfizer announced new boxed warnings for their respective products, Rinvoq and Xeljanz. These black boxes now highlight the higher rate of major adverse cardiac events seen versus anti-TNF agents in the Oral Surveillance trial of Xeljanz. As expected, both have also had rheumatoid arthritis indications scaled back, with patients required to have failed at least one TNF blocker. Analysts believe that Abbvie has come off as well as could be expected, with the label wording making it clear that the [major adverse cardiovascular events (MACE)] signal was seen with “another Jak inhibitor”, and no restrictions on duration of use; some were expecting harsher action from the regulator.

We will continue to monitor the pharmaceutical regulatory sector as well as the medical literature for future developments as regards the increased risks of cancers, blood clots, heart problems, and deaths associated with Xeljanz, Olumiant, and Rinvoq.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)

Eli Lilly Attempts to Distance Olumiant From the Ominous JAK Inhibitors Drug Class Safety Issues Flagged by FDA

Xeljanz, Rinvoq, and Olumiant Are the Three Janus Kinase (JAK) Inhibitors Getting "Black-Box" Warnings Revisions, Soon

 

(Posted by Tom Lamb at Drug Injury Watch)

 

In September 2021 the FDA announced it was requiring revisions to the "Black-Box" warnings for Xeljanz, Rinvoq, and Olumiant to include information about the increased risk of various adverse drug reactions, including serious heart-related events, cancer, blood clots, and death. Xeljanz (tofacitinib), Rinvoq (upadacitinib), and Olumiant (baricitinib) are the three Janus kinase (JAK) inhibitors currently approved by the FDA for the treatment of arthritis and other inflammatory conditions. As such, this September 2121 FDA action can be characterized as a JAK inhibitors drug class label change.

For more information about the basis for that JAK inhibitors drug class label change, we point out an excerpt from 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":

We are requiring new and updated warnings for two other arthritis medicines in the same drug class as Xeljanz, called Janus kinase (JAK) inhibitors, Olumiant (baricitinib) and Rinvoq (upadacitinib). Olumiant and Rinvoq have not been studied in trials similar to the large safety clinical trial with Xeljanz, so the risks have not been adequately evaluated. However, since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.

As background, Xeljanz is a Pfizer drug, Rinvoq is an AbbVie drug, and Olumiant is an Eli Lilly drug. Not surprisingly, the pharmaceutical companies AbbieVie and Eli Lilly have attempted to distinguish the safety profile of their respective JAK inhibitors drug product from the various adverse drug reactions that have been observed in the Xeljanz clinical trial referenced by the FDA, above.

For example, there is this Lilly News Release document, "OLUMIANT® Long-Term Safety Profile Established Up to 9.3 Years in Integrated Analysis of More Than 3,700 Patients with Rheumatoid Arthritis", which was issued on November 9, 2021.

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For some analysis and context about that November 2021 Olumiant press release from Eli Lilly, we refer you to this Fierce Pharma news report, "Eli Lilly touts long-term safety data for Olumiant amid classwide scrutiny on JAK meds", published on November 10, 2021. In part, the article dissects a pooled analysis across nine clinical trials -- and one long-term extension study -- in rheumatoid arthritis patients who received Olumiant for up to 9.3 years, which was presented by Eli Lilly at the recent American College of Rheumatology annual meeting.

In the new pooled analysis, the incidence of major adverse cardiovascular events (MACE) for Olumiant was 0.51 per 100 patient-years of exposure, which Lilly said falls within the range in the general rheumatoid arthritis population as described in epidemiological studies. The analysis covered 3,770 patients taking Olumiant at 4 mg and 2 mg doses for a median of 4.6 years.

In a subgroup of patients over 50 years old who had at least one existing heart risk factor, the incidence rate of MACE was higher at 0.77 per 100 patient-years.

That latter patient population was targeted in Pfizer’s postmarketing safety study for Xeljanz. As the New York pharma disclosed earlier this year, Xeljanz’s MACE incidence rate was 0.91 per 100 person-years at the 5 mg dose, compared with 0.73 for TNF blockers. The difference translated into an increased risk of 24% for Xeljanz.

As for the cancer rates, the age-adjusted number for Olumiant was 0.92 per 100 person-years, which Lilly again said appeared similar to the general U.S. population. In the Pfizer trial, Xeljanz recorded a cancer rate of 1.13, compared with 0.77 for TNF inhibitors.

While Eli Lilly, AbbieVie, and Pfizer are jockeying for the future market share of Olumiant, Rinvoq, and Xeljanz as treatments for arthritis and other inflammatory conditions, the FDA is still considering the details of the JAK inhibitors drug class "Black-Box" warnings label change it announced in September 2021.

Our law firm is investigating possible drug injury lawsuits for patients who used Olumiant, Rinvoq, or Xeljanz and then suffered one of the serious side effects associated with those JAK inhibitors drug by the FDA.  In particular, heart problems such as heart attacks, strokes, pulmonary embolism (PE), and deep vein thrombosis (DVT), as well as cancers such as lymphoma and lung cancer. Feel free to contact us if we can be of assistance to you or someone you know.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

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Xeljanz Risks of Cardiovascular Events, as Well as Cancers, Cause More Xeljanz Use Limitations

October 2021 UK's MHRA Xeljanz Action Follows September 2021 FDA Xeljanz Drug Safety Communication Update

 

(Posted by Tom Lamb at Drug Injury Watch)

 

On September 1, 2021, we posted this article, "Xeljanz: FDA Warnings Updated: There are Higher Rates of Blood Clots and Deaths for Both Doses of Xeljanz, Now", in which we listed the five Drug Injury Watch articles we wrote earlier in 2021 about Xeljanz drug safety developments. Now we are covering the latest drug regulatory action taken due to the Xeljanz risk of cardiovascular events as well as the Xeljanz risk of cancers, or malignancies, this one by the UK's Medicines and Healthcare products Regulatory Agency (MHRA).

This Drug Safety Update document, "Tofacitinib (Xeljanz▼): new measures to minimise risk of major adverse cardiovascular events and malignancies", issued by the MHRA on October 6, 2021, states that Xeljanz should not be used by these patients in the groups identified below unless there is no suitable drug treatment alternative:

• people older than 65 years of age;
• people who are current or past smokers;
• people with other cardiovascular risk factors, such as diabetes or coronary artery disease;
• people with pre-existing cancer or malignancy risk factors.

As regards the Xeljanz side effects findings underlying these new Xeljanz use limitations, from the Safety Review part of this October 2021 MHRA Xeljanz document:

Study ORAL Surveillance (A3921133) was a large, randomised, active-controlled, clinical safety trial to evaluate the safety of tofacitinib versus tumour necrosis factor (TNF)-alpha inhibitors....

The co-primary endpoints of study A3921133 were adjudicated major adverse cardiac events and adjudicated malignancies (with the analysis excluding non-melanoma skin cancer)....

In 2021, final results from study A3921133 showed tofacitinib to be associated with an increased incidence of non-fatal myocardial infarction and malignancies, particularly lung cancer and lymphoma.

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About the Xeljanz risk of cardiovascular events, we find this important information in the October 2021 MHRA Xeljanz document:

Predictive factors for development of myocardial infarction (fatal and non-fatal) were identified using a multivariate Cox model with backward selection. These factors were age older than 65 years, male sex, current or past smoking, history of diabetes, and history of coronary artery disease (which includes past myocardial infarction, coronary heart disease, stable angina pectoris, or past coronary artery procedures).

And about the Xeljanz risk of cancers, that document provides this information:

Predictive factors for development of malignancies (excluding non-melanoma skin cancer) were identified using a multivariate Cox model with backward selection. These were age older than 65 years and current or past smoking.

We will watch for possible additional drug regulatory actions due to the Xeljanz risk of cardiovascular events as well as the Xeljanz risk of cancers, and report significant developments here.

Our law firm is handling Xeljanz drug injury lawsuits for patients with cases of Xeljanz causing heart problems such as heart attacks, strokes, pulmonary embolism (PE), and deep vein thrombosis (DVT), as well as Xeljanz causing lymphoma, lung cancer, and other cancers. Feel free to send me an email if we can be of assistance to you or someone you know.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)

Xeljanz: FDA Warnings Updated: There are Higher Rates of Blood Clots and Deaths for Both Doses of Xeljanz, Now

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....

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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.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)