Extended CMV Prophylaxis After Kidney, Pancreas Transplants Lowers Risk, Costs

Deborah Brauser

September 17, 2009

September 17, 2009 — Increasing the period of preventive treatment with valganciclovir from 3 to 6 months after kidney and/or pancreas transplantation can reduce the risk for cytomegalovirus (CMV) disease, leading to significant overall cost savings, according to results of a retrospective study reported online today in the Journal of the American Society of Nephrology.

"[CMV] infection remains one of [the] most common opportunistic infections in solid organ transplant patients despite availability of specific and efficacious antiviral drugs," write Fu L. Luan, MD, from the Department of Internal Medicine, Division of Nephrology, University of Michigan in Ann Arbor, and colleagues. In addition, the highest incidence of CMV disease is seen in solid organ transplant patients who have a negative CMV serology and receive an organ from a positive CMV serologic donor, with or without prophylaxis.

"Although the risk for CMV disease persists for life, the majority of cases occur shortly after completion of prophylaxis, often within the first year after transplant," the authors explain.

Because the optimal duration of prophylaxis remains unknown, Dr. Luan and team sought to examine the incidences of CMV infection and disease, as well as the cost-effectiveness of 6- vs 3-month prophylaxis with valganciclovir.

The investigators examined data from 222 seronegative patients who received seropositive kidney and/or pancreas transplants between March 2002 and March 2007. All patients received a daily 450-mg dose of valganciclovir for either 3 months (n = 131; mean age, 44.5 years; 64.1% men) or 6 months (n = 91; mean age, 45.8 years; 68.1% men) during 2 consecutive periods.

The participants were then followed up for 12 months after completion of prophylaxis (15 months total for the 3-month group and 18 months total for those in the 6-month group) to assess the incidence of CMV infection and disease.

Immunosuppression included cyclosporine or tacrolimus and prednisone. For the cost-effective analyses, both direct and indirect costs were considered.

The researchers found a total of 54 cases of CMV infection (24.3%) during the entire study period, as documented by CMV viremia.

Six-Month Prophylaxis Reduced Risk

The overall incidence of CMV infection for the 3-month group was 26.7% vs 20.9% in the 6-month group and 24.4% vs 12.1%, respectively, for incidence of CMV disease.

Although the 6-month prophylaxis was associated with a significant 26% risk reduction in CMV disease (risk ratio, 0.74; 95% confidence interval [CI], 0.60 – 0.93; P = .02), it showed only a 12% risk reduction in CMV infection (risk ratio, 0.88; 95% CI, 0.69 – 1.12; P = 0.32), which was not statistically significant.

In addition, Kaplan-Meier analyses showed that the extended 6-month prophylaxis, combined with protocol-driven testing for CMV viremia, resulted in a statistically significant improvement in disease-free survival (log-rank, P = .003), although the same improvement was not seen in infection-free survival.

Cost-effectiveness analyses showed that 6-month prophylaxis combined with the 1-time viremia determination at the end of the prophylaxis period incurred an incremental cost of $34,362 and $16,215 per case of infection and disease avoided, respectively, and $8,304 per 1 quality-adjusted life-year gained.

Sensitivity analyses supported the cost-effectiveness of 6-month prophylaxis over a wide range of valganciclovir and hospital costs, as well as variation in the incidence of CMV disease.

Limitations of the study included its design, which compared 2 sequential cohorts during 2 different time periods, and that the 2 groups had significant different uses of immunosuppression during the study.

"This study showed that extending prophylaxis to 6 [months], combined with one-time CMV viremia determination at the end of prophylaxis period, is effective in reducing the incidence of CMV infection and disease in...kidney and/or pancreas transplant patients," the authors write. "Furthermore, the cost-effectiveness analyses showed that such an approach saves dollars per [quality-adjusted life-year] gained."

But the authors point out that the rate of CMV infection and disease is still too high. "Additional studies are needed to test newer approaches to further reduce the incidence of CMV disease, which can have a significant impact on long-term graft and patient survival," they conclude.

The study authors have disclosed no relevant financial relationships.

J Am Soc Nephrol. Published online September 17, 2009.