High Cost of Arthritis Relief

Adverse side effects temporarily shelve a promising drug

When Eli Lilly & Co. introduced Oraflex last May, the new anti-inflammatory drug was hailed as a breakthrough for the 30 million Americans who suffer from arthritis. Oraflex (chemical name: benoxaprofen) seemed to be less irritating to the stomach than aspirin, the staple treatment for arthritis victims. The drug produced side effects, notably an increased sensitivity of the skin and nails to the sun, but these seemed minor compared with the benefits.

Within three months, however, the promise turned to peril. Several consumer organizations, including Ralph Nader's Health Research Group, went to court seeking a ban on the drug as an "imminent danger." Last week, spurred by reports that 72 Oraflex takers had died and hundreds had been injured in Britain and the U.S., Lilly said that it was recalling all supplies of the drug. Earlier that day Britain's Health Ministry suspended the supply and promotion of the drug for 90 days "on grounds of safety." Meanwhile U.S. officials were considering whether to prosecute the giant international drug firm ( 1981 pharmaceutical sales: $1.7-billion) for not fully informing the Food and Drug Administration about the serious adverse reactions to Oraflex.

Lilly's action followed hearings before a House subcommittee, during which FDA Commissioner Arthur Hayes Jr. said reports of 61 Oraflex-linked deaths in Britain and eleven in the U.S. were under investigation. An internal FDA memo given to the committee charged that in its application for approval of Oraflex in 1980, Lilly had seriously underreported the incidence of some negative side effects, such as failing to acknowledge 65 out of 173 cases of nonfatal adverse reactions. (It did report them later.) The memo said that some of the firm's reports to the FDA were "untrue or incomplete," and that Lilly had no explanation for the incomplete reporting. But not all the blame is attached to Lilly. The head of the FDA'S office of new-drug evaluation, Dr. Robert Temple, said that when Lilly later submitted reports that mentioned jaundice as a possible side effect, the FDA was so swamped with paperwork that it overlooked the information, and physicians were not warned of that danger.

The suspension of Oraflex in Britain, where it had been sold for the past two years under the name Opren, took place years under the name Opren, took place after the Committee on Safety of Medicines, the equivalent of the FDA, reported that it had received notice of more than 3,500 adverse reactions linked to the drug, including the 61 deaths, many of them associated with liver, kidney or gastrointestinal damage. U.S. consumer groups contend that there was no way that Lilly could not have known about the 28 British deaths that occurred prior to the drug's U.S. approval in April. Indeed, accounts of some deaths from liver disease, all among the elderly, were reported to the government in late 1981 and appeared in the Brit ish Medical Journal in May.

Not long afterward, Lilly sent out a letter to U.S. physicians emphasizing that elderly people with impaired kidney or liver functions should not be given the full recommended dosage of the drug. Last week a Lilly research vice president denied knowing about the British fatalities from liver disease until informed by the FDA in May. For his part, FDA Commissioner Hayes testified that his agency did not learn of them earlier because "we don't have the wherewithal to solicit information from all countries where a drug is used."

Lilly, despite its voluntary withdraw al of Oraflex, continues to defend the drug. Oraflex has had "demonstrable good results" on the 1.5 million patients who have taken it, Lilly maintains, and is "safe and effective when used as directed." In an earlier statement, Lilly took "vigorous exception to any implication that it has withheld data, maintained inadequate records or failed to comply with the scientific requirements of the FDA."

With any powerful drug, there is always a trade-off between the primary, beneficial effect and the cost in deleterious side effects: anticancer drugs kill healthy cells as well as malignant ones, and some drugs that relieve intense pain are highly addictive. A thorough review of the findings on Oraflex may show that given its benefits, the risks are as acceptable as those for other drugs in its class, including, significantly, aspirin. On the other hand, it may find that deliberate or inadvertent failure by Lilly to provide necessary but damaging information about Oraflex, coupled with a sloppy performance by the FDA, allowed on the market a drug whose risks were too high.

This file is automatically generated by a robot program, so viewer discretion is required.