Advisors Express Concerns About Immune Effects, Drug Interactions
By Steve Mitchell, MS
WebMD Medical News
Reviewed by Jacqueline Brooks, MBBCH, MRCPsych
Aug. 16, 2001 (Washington) -- Rheumatoid arthritis sufferers soon could have a completely new type of drug available to them. A panel of experts convened by the FDA recommended Thursday that this medicine is safe and effective and should be approved.
The drug, which is called Kineret and is given by injection, is a recombinant interleukin-1 receptor antagonist. Interleukin-1 receptor antagonists balance interleukin-1 activity to reduce inflammation. However, with persistent activation of the immune system in rheumatoid arthritis, they are overwhelmed.
Three clinical trials involving nearly 2,000 patients with rheumatoid arthritis found that more patients receiving Kineret plus other arthritis drugs experienced relief from their symptoms than patients receiving only the other drugs.
Panel members agreed, however, that Kineret appears to be less effective at relieving symptoms than some of the newer arthritis drugs recently made available. Several members justified voting for its approval by noting that Kineret might help patients who fail to improve on the other arthritis therapies.
These types of patients were not included in clinical trials, so there is no data to show whether it will help these patients or not, pointed out Jay Siegel, MD, of the FDA.
Even so, panelist James Williams, MD, of the University of Utah School of Medicine, noted that Kineret is just as effective as some older arthritis drugs that are still in use.
The advisors did express concern that the drug may cause leukopenia in some people. They requested that this risk be noted in labeling, as well as a statement to advise physicians that they should monitor for it.
Williams said he thinks the drug is just as safe as current standards of therapy. In addition, "a lot of drugs cause leukopenia, and we're used to monitoring for it," he said.
However, panel member David Felson, MD, of the Boston University School of Medicine, said, "I think the ... safety issues are substantial." Felson voted against approval.
The committee was also concerned about combining Kineret with a commonly used class of arthritis drugs known as tumor-necrosis-factor inhibitors, or TNF inhibitors, which includes infliximab and etanercept. Clinical trials found that patients taking both types of drugs were more likely to develop serious infections, such as pneumonia.
This is a major concern; many patients take TNF inhibitors because they have been shown to slow down the structural damage that rheumatoid arthritis can cause. In addition, combining different types of arthritis drugs is becoming standard practice across the U.S., Michael Schiff, MD, of the Denver Arthritis Clinic, tells WebMD.
The data suggest that this combination is "dangerous and could kill people," Felson said. He recommended that the drug carry a warning that it not be given in conjunction with TNF inhibitors.
Several members agreed with this recommendation.
Schiff, who worked on the clinical trials with Amgen but is not financially connected to the company, notes that there are a substantial proportion of rheumatoid arthritis patients who fail on currently available therapies, so there is a need for a new type of drug, such as Kineret. "I hope the FDA approves it so we can use it in the clinic," he tells WebMD.
The FDA generally follows the advice of its advisory panels but is not bound by their recommendations.