Actemra Linked to Heart Attacks and Deaths, But Label Remains Unchanged

Washington, DCA recent presentation at the 2017 Annual Meeting of the American College of Rheumatology identified various factors that might predict the capacity for a patient suffering from rheumatoid arthritis (RA) to have success in tapering dosage of biologic medication such as Actemra (tocilizumab). The presentation was based on a study conducted by Dr. Takaaki Komiya and colleagues from Yokohama City University Graduate School of Medicine. However, according to WebMD (11/06/17), there was no mention of Actemra linked to heart attacks and deaths.

That’s not surprising, given a product label that STAT (06/05/17), a sister publication of The Boston Globe, identified back in June as sorely lacking. STAT reviewed more than a half-million report of Actemra side effects since tocilizumab first appeared on the market in 2010. Their investigation found clear evidence of risk for heart attack and heart failure, stroke and other issues: risk that was at the very least equally high, or higher than competing drugs prescribed for RA.

STAT noted that over 1,000 patients prescribed Actemra for RA had died. That fact alone highlights the potential for Actemra lawsuits.

And yet, there is more damning evidence that tocilizumab side effects were predicted even before Actemra achieved approval by the US Food and Drug Administration (FDA) in 2010.

Two years before tocilizumab was approved, an FDA advisory panel convened to debate the merits of approving Actemra. One of the participants, according to the STAT report was Dr. David Felson, a rheumatologist from Boston University. Felson had noted that blood test data from trial participants showed elevated levels of cholesterol and triglycerides, which suggested to the observer that tocilizumab, might well trigger serious heart issues over time.

The Vioxx debacle came to mind. Vioxx (rofecoxib) was an anti-inflammatory drug approved in 1999 but withdrawn five years later by manufacturer Merck & Co. over concerns related to increased risk for cardiovascular issues. In the official transcript of that 2008 meeting, Felson said “I can foresee the possibility that in five years there’s another hearing like the one on Vioxx, where the cardiologists … [sic] say to us, what were you guys thinking when you approved this drug?”

In the end, Felson and colleagues recommended Actemra be approved, provided manufacturers Roche and Genentech conduct multiyear studies going forward to monitor for cardiovascular events and other unforeseen issues, and to update the product label accordingly.

However, it is alleged the Actemra product label has not been updated in spite of numerous reports to the FDA of Actemra side effects deemed serious, and at a higher incidence level than that of other RA drugs.

In one example, a doctor reported to the FDA that no other factor could be considered for a fatal bleeding event of the brain suffered by a patient two days after receiving Actemra via intravenous injection. Another doctor, in referencing a fatal heart attack suffered by a 62-year-old woman in 2014, “the company assessed fatal myocardial infarction as related to (Actemra) [sic].” The doctor was referencing Roche and Genentech, the manufacturers of Actemra. The documents were obtained by STAT through an application under the Freedom of Information Act.

It should be noted that Actemra manufacturers petitioned the FDA to add a reference for ‘fatal anaphylaxis’ following the deaths of two patients. That was in 2011. The following year the FDA was petitioned for an expanded indication for Actemra, which is over and above the various situations where doctors can – by law – prescribe a drug for an indication outside FDA approval boundaries.

STAT interviewed a non-expert, consumer representative on the 2008 FDA panel who was identified as the lone dissenting vote with regard to the approval for Actemra. Diane Adronson told STAT that “as a ‘no’ voter, I felt there wasn’t enough data, it was too short-term. There were some red flags,” she told STAT. Those on the review panel who supported the drug did so because they “really believe that the long-term studies will be acted upon,” and that the warning label would be adjusted if needed, she said. “That’s why they voted ‘yes.’”

While studies have been duly carried out, the warning labels have not changed – at least for Actemra side effects related to heart attack, heart failure, or stroke.

However, it is not clear who is responsible for the lack of a label update: the manufacturers, or the FDA.

STAT noted that a full safety review analyzed by the FDA in 2013 noted 3,500 reports to the agency’s adverse events reporting system had come in as of August of 2012. Of those reports there were 118 deaths identified, with 42 deaths linked to either cardiac arrest or myocardial infarction. And yet the FDA said no further label changes were warranted.

This appears to fly in the face of concerns expressed by medical experts who examined the reports and data obtained by the publication. Those experts opined the FDA should immediately consider warnings for heart failure and pancreatitis. While the evidence that Actemra might increase the risk of heart attacks, strokes, and interstitial lung disease (a sometimes-fatal scarring of lung tissue) appeared to be less convincing, the experts nonetheless suggested that further review was warranted, given the Actemra side effects.
Plenty to chew on for plaintiffs contemplating Actemra lawsuits.