Cost-Effective Immunosuppression

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Azathioprine (AZA) could provide comparable protection against transplant rejection to mycophenolate mofetil (MMF) for kidney transplant patients taking a lower dose of a new more powerful formulation of cyclosporine while substantially reducing costs, according to another trial presented during the High Impact Clinical Trials session.

Paolo Cravedi, MD, PhD, assistant professor of nephrology at the Icahn School of Medicine at Mount Sinai Hospital in New York City, explained that in the mid-1990s two trials suggested that MMF provided a significant reduction in acute rejection compared to AZA when used with older formulations of cyclosporine. As a result, MMF, which costs 10 times more per dose, virtually replaced AZA.

“This choice had a major economic impact because switching patients from AZA to MMF over this time period cost over $1 billion,” Cravedi said.

But results from the ATHENA randomized trial presented by Cravedi add to a growing body of evidence that suggests that AZA offers comparable rejection protection to MMF in kidney transplant recipients on low-dose, newer formulations of cyclosporine.

In the trial, 233 patients were randomized to receive MMF or AZA with a low-dose more stable microemulsion formulation of cyclosporin. At 3 years, 31.9% of the MMF patients had developed chronic allograft nephropathy vs. 32.4% of the AZA group and 18.5% vs. 21.1% had biopsy-proven acute cellular rejection. At 1-year posttransplant, 9.2% of the MMF group vs. 7% of the AZA group had subclinical acute cellular rejection and 5% vs. 6.1% had graft failure. The two groups had similar 3-year eGFR, and 16.1% of the MMF group vs. 18.4% of the AZA group successfully tapered their cyclosporine with only one episode of acute cellular rejection in each group.

“When we compared MMF versus AZA with the background of the new cyclosporine formulation, we couldn’t find any benefit of MMF,” Cravedi said. “They are virtually identical in terms of patient survival and graft survival.” Cravedi said switching to AZA could save about $3500 per year per patient in costs.

Lane, who moderated a press briefing on the high impact trials, said the results of ATHENA were “very promising, especially from a cost saving perspective.” However, she cautioned that most kidney transplant patients in the United States are not taking cyclosporine. Instead, tacrolimus is the calcineurin inhibitor of choice at most US transplant centers. Lane said these results would likely also hold true for patients taking tacrolimus, but it would be necessary to do a clinical trial to confirm this. As US policies aim to shift away from dialysis and to more kidney transplants, such potential savings may be even more important.

“Transplants are already more cost efficient [than dialysis],” Lane said. “Saving roughly 90% of the costs of one of the immunosuppressive agents could only make it even more cost-effective.”

“Mycophenolate Mofetil vs. Azathioprine in Kidney Transplant Recipients on Steroid-Free, Low-Dose Cyclosporine Immunosuppression: The ATHENA Trial” Oral Abstract 135