Pittsburgh Reports Continued Success in Cutting Back Need for Anti-Rejection Drugs

The University of Pittsburgh reported continued encouraging results for its against-the-grain approach aimed at enabling new transplant recipients to dramatically reduce their lifelong dependence on a combination of immunosuppressive medications.

Reporting in the journal The Lancet, Dr. Thomas Starzl provided an update on the center's success in enabling kidney, kidney-pancreas, liver and intestinal transplant patients to cutback to only one anti-rejection drug taken in some cases only once or twice a week (see earlier Transplant Week story).

Unlike the standard approach in which transplant recipients are started on high doses of immunosuppressive drugs, the Pittsburgh approach relies on pretreatment with a large dose of thymoglobulin to deplete immune cells in the hours preceding transplantation, followed by twice-daily treatment with just Prograf starting the day after transplantation.

The doctors after about four months begin what is called "spaced weaning" by first reducing the patients' doses of Prograf to once a day.

For the first 18 patients on this regimen, 13 to 18 months after their transplants, the transplanted organ continued to function in 72 patients, and 43 were on "spaced doses" of Prograf, the researchers reported.

• Of the 25 transplant patients with a functioning kidney, one was taking Prograf every other day, six patients were taking it three times a week, 11 patients were on a twice-a-week dose, and seven were taking the anti-rejection drug just once a week.
• Of the 11 liver recipients, three were down to a once-a-week dose, two to twice a week, four to three times a week, and two patients were taking Prograf every other day.
• Of the 12 pancreas recipients, two were on a once-a-week dose, two on a three-times-a-week regimen and one patient was taking Prograf every other day.
• Of the eight small bowel transplant recipients, two were taking Prograf twice a week, one was taking it three times a week and three patients were taking it every other day.

None of the patients has stopped taking the drugs completely .

"Our animal studies indicate that a maintenance dose of [Prograf] given just once a week can prevent the undesirable outcome of chronic rejection, so we believe it wise for the time being to aim for the lowest dose possible short of complete drug discontinuance in our patients," explained Dr. Ron Shapiro, director of kidney transplantation.

More than 500 transplant patients are currently being treated at the University of Pittsburgh under the new protocol, and at a meeting of the American Surgical Association a week earlier, Shapiro presented further updated results for 150 kidney recipients.

He said one year after transplantation, 63 percent were taking reduced drug doses.

"If you had told me this [was possible] two years ago, I wouldn't have believed it," he said.

Other Sources: Lancet, University of Pittsburgh