Valacyclovir Equally as Effective as Ganciclovir in Head-to-Head Study

May 19, 2004 (Boston) — Valacyclovir is equally as effective as ganciclovir in preventing cytomegalovirus (CMV) in renal transplantation, and it may be more cost-effective as well, researchers reported in a poster session here Monday.

Tomas Reischig, MD, and colleagues, from Charles University Hospital in Pilsen, Czech Republic, reported their results at the 2004 annual meeting of the American Transplant Congress, the joint meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.

In the study, 83 patients were randomized to three months of oral therapy with either ganciclovir (1 g once daily) or valacyclovir (2 g twice daily). Twelve patients were given no drugs, and were defined as the "deferred therapy" group. Doses were adjusted according to renal function.

The only patients excluded were those who had seronegative status and had a seronegative organ. There was little difference in immunosuppressive regimens between the groups, with the majority receiving a cyclosporine plus mycophenolate mofetil combination. Three patients from each group were taking sirolimus, and three were taking azathioprine; two patients from the ganciclovir group and three from the valacyclovir group were receiving tacrolimus.

Patients were followed for up to 24 months and monitored for CMV status and rejection.

At one year, 67% of the deferred therapy group, 6% of the ganciclovir group, and 3% of the valacyclovir group had CMV disease. The difference between the two treatment arms was not significant, Dr. Reischig told Medscape. But there was a difference in biopsy-confirmed acute rejection, which occurred in 58% of the deferred therapy group, 34% of the ganciclovir group, and 12% of the valacyclovir group.

There was a higher incidence of treatment failure (defined as death, graft loss, CMV disease, or study withdrawal) in the ganciclovir (19%) and deferred therapy (67%) groups compared with the valacyclovir group (11%). At two years, the patient survival rate evened out for the two treatment groups, at about 89%, though graft survival was slightly lower for the ganciclovir group — about 80%, compared with 90% for the valacyclovir group.

Michel Paquet, MD, from the Hôpital Notre-Dame in Montreal, Quebec, said he was not surprised that the drugs would be equally effective, but he was uncertain why there would be less rejection in the valacyclovir group. "It seems like they have fewer acute rejections, which seems to be an additive effect," he told Medscape.

Dr. Reischig said that the acute rejection rate was highest in ganciclovir with delayed graft function — 15 of those 35 patients had delayed function, and of those, 53% experienced acute rejection compared with 20% of the 7 valacyclovir patients who had delayed graft function.

He also said that the valacyclovir patients had less CMV disease and therefore were more likely to avoid rejection.

Finally, when CMV-associated monitoring and treatment were taken into account, valacyclovir was more cost-effective than ganciclovir, Dr. Reischig said. Over 12 months, those costs were $3,348 (± $2,803) for valacyclovir, $3,539 (± $2,311) for ganciclovir, and $5,651 (± $6,550) for the deferred therapy group.

Valacyclovir, approved in the U.S. in 1995 for herpes infections, is sold as Valtrex by GlaxoSmithKline. Ganciclovir, marketed by Roche as Cytovene, is available in intravenous and oral formulations.

ATC 2004: Abstract 1225. Presented May 18, 2004.

Reviewed by Gary D. Vogin, MD