FDA urges more caution over TNF blocker infections

WASHINGTON (Reuters) - U.S. health regulators ordered stronger warnings for prescription drugs to treat rheumatoid arthritis, Crohn's disease and other conditions on Thursday after dozens of patients contracted severe fungal infections and died.

The so-called TNF blocker medications include Johnson & Johnson's Remicade, Abbott Laboratories Inc's Humira, UCB SA's

Cimzia and Amgen Inc and Wyeth's Enbrel, the U.S. Food and Drug Administration said.

Current warnings "must be upgraded to strongly warn doctors to consider" the possibility of fungal infections in patients who are seriously ill or who are not responding to current antibiotics, said Jeffrey Siegel, a clinical team leader in the FDA's Division of Anesthesia, Analgesia and Rheumatology Products.

"These infections need to be identified early enough so that treatment is not delayed," he added.

Rheumatoid arthritis, Crohn's disease and other diseases targeted by the four medications are caused in part by inflammation. The drugs work by suppressing the immune system to combat such flare-ups, but that can leave patients vulnerable to other complications.

Agency officials reviewed 240 reported infections caused by the fungus Histoplasma capsulatum in patients taking Enbrel, Humira or Remicade.

In at least 21 of the 240 cases, the infection was initially not caught in time by doctors and 12 of those 21 patients died, the FDA said.

The agency reviewed one reported case of histoplasmosis involving UCB's Cimzia, which was just recently approved in April.

Overall, 45 patients died, Siegel said.

The FDA has also received reports of other fungal infections including coccidioidomycosis and blastomycosis, in patients taking the tumor necrosis factor, or TNF, alpha blockers.

Strong "black box" warnings about the serious risk for fungal and other infections are already on some of the drugs' labels, but the FDA wants them to be consistent for all products and to be strengthened in an effort to draw more attention to histoplasmosis, Siegel said.

Part of the problem is that patients and doctors may not quickly recognize the infection, delaying treatment that could help prevent hospitalizations or deaths, Siegel said.

The FDA said the companies must submit new warning language for approval within 30 days or give a reason to protest the changes.

Abbott spokeswoman Laureen Cassidy said Humira's label already notes histoplasmosis risk but the company would comply with the agency's request.

Representatives for UCB and Amgen also said their companies would cooperate with the FDA. Wyeth referred calls to Amgen. Representatives for Johnson & Johnson's Centocor Inc unit that makes Remicade did not respond to requests for comment.

Abbott's shares closed down 2.4 percent at $56.57 in afternoon trading, while Amgen and Wyeth shares closed down 3.5 percent at $60.88 and 3.6 percent at $41.05, respectively. Johnson & Johnson shares fell 1.5 percent to close at $70.45.

UCB's shares earlier closed down 2 percent on the Brussels exchange.

Most of the infected patients lived in the middle part of the United States, near the Ohio River and Mississippi River valleys, the FDA said.

Histoplasmosis targets the respiratory system and can be difficult to diagnose because of its flu-like symptoms, such as a fever and cough, Siegel said, adding that current treatments for serious cases include drugs that can be highly toxic.

The FDA is also reviewing whether the TNF blocker drugs are linked to an increased risk of cancer in children and teenagers. Siegel said the agency in June committed to concluding its review in 6 months.

"We intend to meet that timeline," he added.

(Additional reporting by Lisa Richwine; editing by Gerald E. McCormick and Andre Grenon)