Biologic medicine linked to deaths

FDA has gotten 34,000 fatality reports since 2004

As her kidneys and liver failed and a 106-degree temperature smoldered for days, Helen Tschannen was being kept alive on a ventilator. Doctors were not certain what was happening, but the family knew this: Tschannen, 77, did not want to be kept alive by machines. After 21 days in an Illinois hospital, they gathered at her bedside. A nurse unhooked the equipment. Tschannen took one breath and died. It was Oct. 19, 2004. In the weeks after Tschannen’s death, her family learned she had suf

fered from a common fungal infection known as histoplasmosis. For most people, it produces no symptoms or only mild ones.

Tschannen was at special risk of a bad infection because of a drug she started taking a few months earlier to tame her rheumatoid arthritis.

The drug, Remicade, had been approved for her condition in 1999. It was at the forefront of a class of drugs known as biological medicines, or biologics, that treat autoimmune diseases of the skin, joints and gastrointestinal system.

In the past 20 years, the drugs – which can cost $40,000 a year – have flooded the market. Ads for several, including Humira and Cosentyx, are fixtures on television, promising relief of gastrointestinal symptoms or clearer skin with “sexy elbows.”

Preliminary numbers for 2018 show that group of biologics was on pace to top 6 million prescriptions last year, a nearly 50% increase from 2013, according to data from IQVIA, a pharmaceutical market research firm.

The drugs are effective in treating rheumatoid arthritis, psoriasis and other autoimmune disorders. They often lead to significant improvement in symptoms, even remission.

Less known to the public: They leave patients more susceptible to infections and other serious side effects.

Tschannen’s case is one of at least

34,000 reports to the Food and Drug Administration of people who died while using biologic drugs since 2004, according to an extensive analysis by the Milwaukee Journal Sentinel of data from the agency.

More than 1 million “adverse events” were reported in people using the drugs during that time, including nearly 500,000 that were serious, the investigation found. The FDA’s database does not verify any cause-and-effect relationship between the drug and what happened.

Among all prescription drugs over the past 15 years, the biologics Humira and Enbrel are the most-cited in the FDA’s database, the Journal Sentinel review found.

Humira was linked to 169,000 reported serious adverse events and 13,000 reports of deaths, followed by Enbrel with 135,000 serious events and 8,000 deaths.

There are 21 biologic drugs on the market, up from seven in 2004; two others were launched but taken off the market. Many of the drugs are approved to treat multiple conditions.

Since 2000, the FDA has issued more than 25 warnings and safety communications regarding biologic drugs or required the drugs’ labels be updated to list information about serious risks – all after the drugs were approved for use in patients.

The Journal Sentinel review found warnings for fungal and bacterial infections, as well as a rare viral brain infection. Other warnings included tuberculosis, a flesh-eating bacteria, neurological conditions, liver and heart failure and lymphoma and other cancers.

In 2001, the FDA issued a “black box” warning, its most stringent, alerting doctors to the potential of histoplasmosis infections in patients on biologic drugs.

It was not until 2008 – four years after Tschannen’s death – that the FDA issued such a warning for Remicade and three related drugs, Humira, Enbrel and Cimzia. The warning noted fungal infections “are not consistently recognized in patients” taking those drugs.

According to data from the U.S. Centers for Disease Control and Prevention, histoplasmosis infections leading to hospitalization increased by 15% a year from 2001 to 2012 with a reported mortality rate of 20%. Biologics are “likely to be one of the factors behind the increase in hospitalizations,” CDC spokeswoman Brittany Behm said.

FDA spokesman Nathan Arnold said there is intense scrutiny of drugs by his agency before they are approved, but he acknowledged “much work still remains to monitor approved drugs over time.”

Linda Davis, a spokeswoman for Johnson & Johnson, the maker of Remicade, said in a statement that Remicade’s safety has been established in nearly 3 million patients worldwide.

“Enbrel’s benefits outweigh its risks,” said Trish Hawkins, a spokeswoman for Amgen, the maker of Enbrel.

Jillian Griffin, a spokeswoman for Abbvie, said Humira “has a well-established safety profile and is a trusted treatment that is supported by more than 16 years of physician and patient experience.”

Tschannen, 77, who died of a histoplasmosis infection, went to the doctor as soon as symptoms emerged.

Tschannen had suffered from rheumatoid arthritis for years.

She had been taking three other drugs for the condition and added Remicade a few months before she got ill. The drug was given by infusion every few weeks.

“She only had two doses,” said her daughter Bev Webber, a retired nurse.

She said she realized Remicade had helped many patients.

“I also know my mother died a horrible death,” she said. “I wish we had never heard of this medication.”

This story was produced with the support of the National Institute for Health Care Management Foundation. Officials from the organization played no role in the reporting, editing or presentation of the project.

BEV WEBBER Bev Webber, left, a retired nurse, says her mother, Helen Tschannen, had only two doses of Remicade. “I wish we had never heard of this medication,” Webber says.