Clues to Why Rheumatoid Arthritis Drug Humira Fails Some Patients
Posted Apr 12 2011 12:19pm
Nearly a third develop an immune reaction to the drug that thwarts its effectiveness, study finds.
By Jenifer Goodwin HealthDay Reporter
TUESDAY, April 12 (HealthDay News) -- In a new study, close to a third of patients taking the arthritis drug Humira developed an immune system reaction to it that rendered it ineffective.
Researchers say the finding helps to explain why some people get relief from their rheumatoid arthritis symptoms while on Humira (adalimumab), which is made by Abbott Laboratories, while others gain little or no benefit. Humira belongs to a class of drugs known as biologics.
In those people for whom the drug is ineffective, the immune system realizes the drug is a foreign substance and develops antibodies to it, researchers explained. Those antibodies bind to the drug and prevent it from working.
"What the publication shows is that Humira, like many other biologic agents, may induce an immunological response against the drug," said senior study author Dr. Gerrit Jan Wolbink, a rheumatologist at Jan van Breemen Research Institute in the Netherlands. "The immunological response works against the drug. This is one of the explanations why some patients do not respond the way we hope they will."
Patients who were also taking methotrexate, another arthritis drug and an immunosuppressant, were less likely to develop the antibodies, according to the study in the April 13 issue of the Journal of the American Medical Association.
Researchers followed 272 patients taking Humira for about three years.
About 28 percent developed immune system antibodies against the drug. The reaction tended to happen within the first few months of starting treatment: About 67 percent of those who developed antibodies did so during the first 28 weeks.
Patients without antibodies had more of the drug circulating in their blood. Lower levels of the drug are a sign that the body's immune system is fighting the drug and it's being removed from the body, Jan Wolbink explained.
Whether or not patients developed antibodies was also linked to whether they got relief from their rheumatoid arthritis while on Humira.
Nearly half -- 48 percent -- of those without antibodies experienced a significant reduction of their arthritis symptoms while taking the drug, while only 13 percent of those who developed antidrug antibodies got similar relief.
And while 34 percent of patients without antibodies experienced remission, only 4 percent of those who developed antibodies did.
Patients who developed antibodies were also more likely to drop out of the study because of "treatment failure."
Humira is a tumor necrosis factor (TNF) inhibitor, which works by blocking the action of TNF, a substance known as a cytokine that contributes to the inflammation of rheumatoid arthritis and other conditions.
"If you make antibodies, then Humira doesn't block the action of TNF, and it doesn't work," Jan Wolbink said.
Dr. Olga Belostotsky, a rheumatologist and chief of allergy and immunology at Lennox Hill Hospital in New York City, said the research helps explain why some patients don't respond to Humira, and yet they do respond when switched to another drug in the same class of TNF inhibitors.
"It's because they don't have antibodies to the other drugs, even when it's another drug in the same group of medications," she said.
Belostotsky said the research suggests it's very important that patients start methotrexate to suppress the immune system before starting Humira.
What isn't known is why those 28 percent of patients developed antidrug antibodies while the rest didn't.
"Why antibodies develop in some people more than the others is unclear, and why people react more to some drugs than others is unclear," Belostotsky said.
(SOURCES: Gerrit Jan Wolbink, M.D., Ph.D., rheumatologist, Jan van Breemen Research Institute, Amsterdam, Netherlands; Olga Belostotsky, M.D., Ph.D., rheumatologist and chief, allergy and immunology, Lenox Hill Hospital, New York City; Journal of the American Medical Association, April, 13, 2011)