Amid warnings, Partners to cut anemia drug doses

Amid warnings, Partners to cut anemia drug doses
Higher use tied to death risk
By Christopher Rowland, Globe Staff | December 28, 2006

Boston’s largest hospital system, Partners HealthCare , says it plans to reduce doses of antianemia drugs given to kidney disease and chemotherapy patients in response to warnings that aggressive use increases the risk of fatal heart attacks and strokes.

Partners, the nonprofit parent corporation of Harvard University-affiliated Massachusetts General Hospital and Brigham and Women’s Hospital , would be the first hospital network in the country to order the reduction in dosage levels. The plan contrasts with practices at the largest for-profit dialysis chains, which have said they do not intend to cut doses.

Antianemia drugs have been the subject of debate among kidney doctors, dialysis clinics, and federal regulators since November, when the New England Journal of Medicine published results of a halted clinical trial that showed that Procrit, one of the drugs, was responsible for more deaths when given in larger doses. As a result, the Food and Drug Administration warned doctors not to use the drugs, known generically as epoetin, to boost red blood cell counts excessively .

“Too much of a good thing can have bad side effects, and that seems to be what’s happening with epoetin,” said Dr. Jessica Dudley , a Brigham and Women’s Hospital physician who is part of a task force examining Partners’s use of specific high-cost, heavily prescribed drugs.

People suffering from kidney failure or undergoing chemotherapy almost always become anemic because their bodies do not produce enough red blood cells. Antianemia drugs are synthetic hormones that trigger production of red blood cells. Without the drugs, patients would have to receive blood transfusions. In addition to Procrit, made by Johnson & Johnson, the drugs include Amgen Inc.'s Epogen and Aranesp. Under Amgen’s patent, dialysis clinics can use only Epogen.

The New England Journal of Medicine article documented a clinical trial of Procrit. The trial, called CHOIR, attempted to elevate red blood cell counts in kidney disease patients close to normal levels, but was stopped prematurely by a safety review committee.

The study findings appeared to support earlier trials of epoetin in kidney and cancer patients that found an increased risk of death or other health problems with treatments that were more aggressive than what the FDA recommends.

Last month, the FDA strongly urged doctors to strictly observe its guidelines, which say antianemia drugs should not be used to raise red blood cell counts above 12 grams per deciliter of blood. In the trial, researchers sought to elevate red blood cell counts above 13 grams. About half of dialysis clinic patients in the United States are routinely given epoetin doses that drive their red blood cell counts higher than 12 grams, according to federal Medicare data.

Partners said its new dosing guidelines are designed to ensure the drug is not used to exceed the recommended 12 grams and will likely be adopted in early 2007. The initiative is being led in part by Dr. Ajay Singh , the Brigham and Women’s Hospital kidney doctor who oversaw the CHOIR trial and was surprised by the negative results.

“Clinical trials make us humble,” Singh said.

The Partners move is expected to influence other hospitals, but is unlikely to affect for-profit kidney dialysis clinics, including the nation’s two largest chains, Fresenius North America and DaVita Inc. Under a 1972 federal law, Medicare pays for most dialysis treatment in the United States, spending about $2 billion annually on Epogen. Medicare guarantees dialysis clinics a profit of at least 6 percent on the drug, and last spring it loosened its reimbursement guidelines to allow its use to raise blood cell counts as high as 13 grams per deciliter.

Medical directors for Fresenius North America and DaVita have said they won’t modify their use of the drug because they do not believe the data published in the CHOIR study applies to dialysis patients. The trial tested the drug in patients with earlier-stage kidney disease who did not yet need dialysis .

“These are different populations of people,” said Dr. J. Michael Lazarus, Fresenius medical director. DaVita said its medical director, Charles McAllister , was unavailable for comment.

Medicare said its reimbursement policy accounts for how individual patients respond to anemia treatment. Amgen said it has always recommended following the lower FDA dosing guidelines for Epogen and that Medicare’s policy change has not encouraged more use of the drug. The company declined to comment on Partners HealthCare’s plan to reduce doses.

Sales of Epogen for dialysis patients are expected to decrease about 3 percent to 5 percent as a result of doctors’ concerns about the CHOIR study, said Michael Aberman , an analyst for Credit Suisse in New York who rates Amgen’s stock as overpriced. A more dramatic drop is unlikely, he said, unless Medicare payment policy changes, or the National Kidney Foundation tightens its own anemia treatment guidelines, which were also loosened last spring.

“The bottom line is that most of the dialysis providers have a financial incentive to continue to use epo, which underlines how important it is for [Medicare] to change their reimbursement,” Aberman said.

Partners, a nonprofit organization, said it did not consider the potential loss of revenue when deciding to cut back on epoetin use. “This system doesn’t do things because we can do them and get paid for them,” said Dudley. “We do them because they are the right things for patients.”

The Partners guidelines have been drawn up by committees of doctors and are being reviewed at the system’s hospitals, which include Newton-Wellesley Hospital in Newton, North Shore Medical Center in Salem, and Faulkner Hospital in Boston.

But until there is consensus nationwide, dialysis patients will likely receive different doses of antianemia drugs depending on where they seek care. Dr. Wayne M. Trebbin , who treats dialysis patients at North Shore Medical Center and at a DaVita clinic in Salem, where he is medical director, is among the doctors who are wondering where the science and debate over reimbursements will lead. Although federal data show DaVita clinics nationally treat anemia aggressively and have large numbers of patients with red blood cell counts above FDA guidelines, Trebbin said the target count for patients at the Salem clinic has always been 11.5 grams per deciliter, below FDA guidelines.

“This is in a state of flux right now,” he said of the dosing debate. “We don’t know what the final answer is going to be.”

Christopher Rowland can be reached at