Rheumatoid Arthritis Drug Humira Linked to Psoriasis, Herpes, Possibly Cancer
"Arthritis Drugs Linked to Risks From Infection," flashed headlines from 622 news sites in early September.
"FDA Posts List of Drugs That May Be Unsafe," flashed 542 different headlines the next day.
In six short years, Humira (adalimumab), Abbott Laboratories' rheumatoid arthritis (RA) medication, cited in both articles, has gone from wonder drug to wonder-how-it-got-approved drug; more results from safety reviews are expected in November.
Forty-five people have died from invasive fungal diseases while taking Humira and its pharmacological cousins Enbrel, Remicade and Cimzia, the FDA said last week in recommending stronger warnings. That's almost 20 percent of the 241 people who were diagnosed with fungal diseases since the drugs came on market.
The opportunistic infections, clustered in fungal endemic areas like the Ohio and Mississippi river valleys, can appear like the flu and be missed by physicians, the FDA cautioned.
Humira also has a place on the FDA's first list of drugs under investigation for "Potential Signals of Serious Risks," newly published on a quarterly basis under a drug safety bill Congress passed last year.
Its potential "signals of serious risks"? Cancers in children and young adults.
As one of the new recombinant DNA monoclonal antibody biologic drugs tantalizing Wall Street, North Chicago, Ill.-based Abbott Laboratories' Humira had a charmed beginning as it came on the market in 2002.
In fact, the FDA was so impressed with Humira's "smart bomb" ability to search out and destroy the body's tumor necrosis factor (TNF), which attacks healthy tissue in rheumatoid arthritis and other autoimmune diseases, it approved the drug three months early.
More than a million people in the United States suffer from RA, a long-term inflammatory disease of the joints that can lead to disability and fatigue and can spread to the skin, lungs and other organs.
And there was more good news as Abbott enlisted PR giant Edelman to leverage the Arthritis Foundation in "educating" doctors about the new drug.
On the basis of pre-marketing presentations from Abbott and makers of drugs like Humira, the FDA Arthritis Advisory Committee announced in 2003 it found no, repeat no, increased risk of lymphoma -- cancer of the lymphatic system -- with TNF blockers.
And Humira had some other starting-lineup advantages.
Though an injectable drug -- and painful at that, say patients -- Humira was the first TNF blocker to use only human cells, not mice and hamster ovary cells, in drug synthesis. Think about that when you're eating dinner.
And, unlike its main competitor in 2003, Johnson & Johnson's Remicade, which a doctor had to administer in the office, you could inject Humira at home!
But even as Abbott lobbied Congress successfully in 2003 to get Humira's $15,000-a-year costs on the Medicare dole and seeded seniors with freebies before Humira's risks -- and especially higher risks for seniors -- were made public, Humira's safety profile had to be revised downward.
Clinical trials in 2004 revealed allergic reactions including anaphylactoid in 1 percent of Humira patients as well as cytopenia, a serious hematologic event, and pancytopenia and aplastic anemia, bone marrow conditions.
And a study at the Mayo Clinic in the May 17, 2006, JAMA found Humira patients faced triple the risk of developing several kinds of cancer and double the risk of getting serious infections. Oops.
Even the Associated Press put on its "ER" hat and observed that while earlier Humira research "focused mostly on one kind of cancer -- lymphoma -- and infections such as tuberculosis and pneumonia," the new Mayo Clinic study "found an apparent link to other cancers, too, including skin, gastrointestinal, breast and lung tumors."
Abbott won approval for Humira for use in the autoimmune diseases psoriatic arthritis and ankylosing spondylitis in 2006, Crohn's disease, the digestive disorder, in 2007 and psoriasis and juvenile rheumatoid arthritis in 2008.
But the bad ink continued.
Congestive heart failure, a lupus-like syndrome, lymphoma, blood disorders, herpes, menstrual disorders, sinus disorders and psoriasis (which Humira was supposed to treat) were some of the side effects appearing in medical journal articles.
Of course, some of the Humira rap comes from its action of suppressing the immune system in diseases where it is overactive. Why wouldn't opportunistic infections result?
Patients and doctors are well warned about the danger of pre-existing infections -- it says "Some patients have died from these infections" right on the package, hello! -- and some patients say the drug is worth the risks.
But another part of Humira's rap stems from the pharma two-step of prescribing uberdrugs for everyday ailments -- recognized or not -- and market blitzing the media before adverse reports and competitors surface.
And Abbott has excelled at the two-step, removing references to the damning JAMA study from Wikipedia, according to a Brandweek blog, and paying $622 million in 2003 to settle an investigation into illegal sales of liquid foods to nursing homes.
When asked by pharmaceutical reporters why Abbott's PR army of Edelman, Young & Rubicam, and Harrison and Star conducted direct-to-consumer advertising on a drug that costs $10,000 or $20,000 a year, Abbott Vice President of Specialty Operations Heather Mason said, "Rheumatoid arthritis is a market where people often don't know what they have for a while" and it is often "misdiagnosed."
Nor is Abbott content with Humira's reputation as a last-resort drug.
Sure, Humira is expensive, paid Abbott consultant Dr. Joel M. Kremer told the New York Times in August, but "inadequately treated rheumatoid arthritis typically leads to multiple joint replacements, lost productivity, lost tax revenue and a greatly diminished quality of life, as well as an increased risk of life-threatening infections and cardiovascular disease. ... You have to consider what it costs to fix a bridge against what it will cost when the bridge collapses."
Abbott consultant Dr. Stephen Hanauer, coincidentally, agreed that early Humira treatment reduces "overall costs" and enhances "patients' quality of life" in "Reviews in Gastroenterological Disorders" in 2007.
Still, the bad ink continues.
In June, the FDA announced a probe into whether Humira heightens the risk of lymphoma, leukemia and melanoma in children receiving it for juvenile idiopathic arthritis -- after receiving 30 reports of childhood cancer over the last 10 years.
While Abbott awaits the November results, don't expect any more free Humira samples.