Oct. 21 (Bloomberg) -- One in four biotechnology drugs causes side effects that led to safety warnings within a decade after the treatments were first sold, a study found.

The results in the Journal of the American Medical Association show close monitoring is needed for the drugs, made from living cells of animals and humans, said researchers from the Netherlands' Utrecht Institute for Pharmaceutical Sciences. The greatest risk came with new drug classes and within the first few years of reaching the market, the study said.

Infections triggered safety alerts for the arthritis medicines Enbrel, sold by Amgen Inc.; Johnson & Johnson's Remicade; and Abbott Laboratories' Humira. ImClone System Inc.'s cancer drug Erbitux got a warning for its ties to cardiopulmonary arrest, while Genentech Inc.'s Herceptin was linked to infusion-site reactions and lung toxicity. The risk from biotechnology products was higher than earlier studies found with conventional pharmaceutical drugs.

``Knowledge of a new drug is incomplete at the time of approval, especially with reference to its safety profile,'' the researchers said. ``Health-care professionals should be aware of the specific risks related to the relatively new class of biologicals to be able to provide a link between the use of the biological and the patient presenting with a clinical problem.''

The researchers tracked all biological drugs approved in the U.S. and Europe from 1995 through 2007, including insulin, blood products, cancer and cardiovascular medicines, and agents to fight infections. Regulators took safety-related actions for 41 of the 174 products approved. Nearly 30 percent of products that had been on the market for 10 or more years were the subject of a safety alert.

Black-Box Warnings

The alerts, including the most stringent black-box warnings included in the product's prescribing instructions, stemmed mostly from injection site reactions, infections, immune system disorders and cancers. Since the first biological was approved in 1982, more than 250 have been sold in the U.S. The drugs now represent about one in four approvals. There were black-box warnings for 17 percent of the biotech medicines. None of the drugs were withdrawn from the market.

Many biotech drugs affect the immune system, raising a risk that the drug may alter its function in unintended ways, the researchers said.

Rituxan, which Genentech sells with Biogen-Idec Inc. for lymphoma, caused rare cases of life-threatening infections called progressive multifocal leukoencephalopathy. The condition is also tied to Biogen's multiple sclerosis drug Tysabri, which was temporarily taken off the market as a result. Last week, Genentech added a highlighted warning about the risk of PML to its psoriasis drug Raptiva.

No Comment

The Biotechnology Industry Association had no immediate comment on the findings, said Stephanie Fischer, a spokeswoman.

A similar review of pharmaceutical products approved through 1999 found a 10 percent chance of a black-box warning within a decade, suggesting the risk may be higher with biotechnology drugs. Differences between the studies make it impossible to directly compare the two types of medications, the researchers said.

The findings show biotechnology drugs should be used with caution, said Lisa Saubermann, a pharmacist and specialist in infectious disease and transplant immunology at the University of Rochester Medical Center. The risks often can be managed by carefully selecting and closely monitoring patients, said Saubermann, who wasn't involved in the study.

``Biological drugs should be used by providers who have experience with them and know about the side effects,'' she said in a telephone interview. ``They should not be used right out of the gate. But sometimes there are no other agents we can use for these patients, because no other therapies work.''

New Method Needed

Regulatory agencies need a better method to identify complications caused by new medicines, said Sidney Wolfe, director of Public Citizen's Health Research Group, a Washington-based advocacy organization. Biotechnology drugs can cause widespread side effects in the body that aren't always understood, said Wolfe. Public Citizen conducted the previous study on conventional drugs.

``There should be much more intensive surveillance at the beginning, and data should be collected in a more orderly way,'' he said in a telephone interview. ``Some of these drugs are screaming for better surveillance so that if problems arise, we'll find them sooner rather than later.''

Wolfe said regulatory agencies like the U.S. Food and Drug Administration need to do more, particularly for biotechnology drugs that aren't as well understood as pharmaceutical products. The FDA has the authority to force the companies to conduct additional studies after new medications are on the market to undercover the risks, he said.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

Last Updated: October 21, 2008 12:57 EDT