Arthritis drugs not as risky as first thought

Nov 8 2006

Researchers now say that two biotech drugs used to treat rheumatoid arthritis, Humira (Abbott Laboratories) and Remicade (Johnson & Johnson), may not raise the risk of cancer and infections as much as was initially feared.

A series of published letters from several teams of researchers show that after a fresh look at the safety of the two drugs, they may double the risk of cancer and infections rather than tripling such risks, as was first stated.

The majority of the researchers along with the U.S. Food and Drug Administration (FDA), believe that patients need to know about the risks but say the benefits mean the drugs should remain on the market.

It was in May that a study showed that Humira, known generically as adalimumab, and Remicade, known generically as infliximab, tripled the risk of cancer, particularly lymphoma, and some infectious diseases such as tuberculosis in patients who used them.

The information had already been included in labels put on the drugs after a directive from the FDA six months earlier.

Dr. Eric L. Matteson, a professor of medicine at the Mayo Clinic, New York and colleagues who did the original study, later re-analyzed the data and added more from other studies they had not considered before; the new analysis showed the cancer risk was 2.4 times greater among patients who used the drugs, and the risk of infectious disease was 1.8 times greater.

Matteson says though the risk is still higher in treated groups than in untreated groups, that is to some extent to be expected as rheumatoid arthritis is an autoimmune disease, in which the immune system mistakenly attacks the joints, and the drugs target TNF-alpha, one of the immune system's signaling compounds.

Matteson says anything that modifies the immune systems has the potential for causing cancers.

Matteson's team is now looking at a third drug in the same class, which they are also concerned about, Enbrel (Amgen), known generically as etanercept.

So far, studies have shown no link between Enbrel and cancer or infectious diseases.

Rheumatoid arthritis affects about 2 million Americans and the drugs approved to treat it often work against skin conditions such as psoriasis, ulcerative colitis and similar autoimmune conditions.

On another issue connected to Matteson's May study, the failure of researchers to fully disclose pharmaceutical-industry connections in the study has resulted in a letter of apology to the Journal of the American Medical Association - JAMA.

Fortunately all those involved in the issue regard both the findings of the study and the methods used as sound and there appears to be no question as to the validity of the science involved.

The problem arose because the researchers failed to tell JAMA they had allowed Abbott Laboratories to review the paper before it was published, because they had a prior agreement to do so. But they did not grant Centocor Inc., the maker of Remicade, the same opportunity as they had no such agreement with that company.

The Mayo researchers also omitted tell the journal they had received $25,000 from Amgen, the marketer of Enbrel, for the training of Dr. Tim Bongartz, one of the study co-authors.

They also failed to note that a TNF drug made by Wyeth was not included in the study, even though they were working with Wyeth on another study.

Matteson says he is embarrassed by the incident which was not intended to mislead; he and Dr. Bongartz have written an apology to JAMA.

Dr. Catherine D. DeAngelis, JAMA's editor-in-chief, says she was concerned as she was first notified of the situation by one of the drug companies involved.

As a result of her concern the Mayo Clinic investigated the issue and instituted conflict-of interest-education for its researchers.

This incident and other occurrences surrounding disclosures has resulted in JAMA tightening its disclosure policy on conflicts of interest and it now requires all authors to disclose all potential conflicts of interest in the 'Acknowledgment' section of the manuscript at the time of submission.

The original study appeared in the May 17, 2005, issue of JAMA. The letters concerning the study are published in the current edition of the Journal of the American Medical Association.