Cost-effectiveness of cidofovir treatment of polyomavirus nephropathy in kidney transplant recipients.

BACKGROUND: BK virus nephropathy (BKVAN) causes about 10% of late kidney graft loss. Cidofovir is widely used to treat BKVAN, but the magnitude of the health benefits and costs are largely unknown. We aimed to evaluate the incremental health benefits and costs of cidofovir and immunosuppression reduction compared with immunosuppression reduction alone in kidney transplant patients with BKVAN. METHODS: A probabilistic decision analytic model was developed to simulate a cohort of kidney transplant recipients aged 45 years and above with BKVAN who received cidofovir treatment compared with those who received standard care. The duration of the cycle was 1 year, and the model terminated when all recipients were deceased. RESULTS: Compared with immunosuppression reduction alone, in the base-case, the incremental health benefits of cidofovir were 0.0061 life-years saved (2.2 days), with savings of $20,756 over the lifetime of a transplant recipient. When varying the most influential variables (the probability of response to treatment and graft loss) between best and worst case scenarios, the incremental health outcomes ranged from -0.967 to 1.093 life-years saved, with incremental costs ranging from an extra $27,313 to saving $20,756. CONCLUSIONS: Compared with immunosuppression reduction alone, based on best available data, cidofovir treatment and immunosuppression reduction for BKVAN seem to be cost saving and improves health outcomes. However, because of weak clinical data, particularly around comparative effectiveness, there is still moderate uncertainty in the incremental cost effectiveness. Adequately powered trials are still needed to better define optimal treatment strategies for BKVAN before cidofovir can be recommended strongly as routine therapy.

Economic evaluation of systemic treatments for cytomegalovirus retinitis in patients with AIDS.

OBJECTIVE: To determine the cost of using systemic therapy to treat newly diagnosed cytomegalovirus (CMV) retinitis in persons with AIDS. DESIGN: Incidence-based simulation model of CMV treatment from a government payer perspective. SETTING: Swiss healthcare system. PATIENTS AND PARTICIPANTS: Patients with AIDS and newly diagnosed CMV retinitis. INTERVENTIONS: Patients were assigned to 1 of 4 treatment regimens for induction and maintenance therapy: (i) intravenous (IV) cidofovir induction and maintenance (cidofovir IV/IV); (ii) IV foscarnet induction and maintenance (foscarnet IV/IV); (iii) IV ganciclovir induction and maintenance (ganciclovir IV/IV); and (iv) IV ganciclovir induction and oral (PO) ganciclovir maintenance (ganciclovir IV/PO). Following a second relapse, patients were assigned to one of the other regimens. MAIN OUTCOME MEASURES: Time to first and subsequent progression, duration of maintenance treatment and direct medical expenditures [1998 Swiss francs (SwF)] . RESULTS: The median time to first progression was longest for cidofovir IV/IV, followed by foscarnet IV/IV, ganciclovir IV/IV and ganciclovir IV/PO. Mean survival was 13 months and mean costs for this period in the base case were lowest in those initially treated with cidofovir (SwF146,742), followed by initial treatment with foscarnet IV/IV (SwF194,809), ganciclovir IV/PO (SwF195,190) and ganciclovir IV/IV (SwF243,964). Costs were most sensitive to changes in efficacy estimates. CONCLUSIONS: Of the regimens studied, initiation of treatment with systemic cidofovir appears least costly over a 13-month period.

Cidofovir in the treatment of cytomegaloviral disease.

OBJECTIVE: To review the clinical pharmacology and microbiology of cidofovir in the therapy of cytomegalovirus (CMV) disease. DATA SOURCES: Pertinent literature was identified via a MEDLINE search (October 1986-February 1997), and data from abstracts presented at recent scientific meetings were also included; unpublished information was provided by the manufacturer. STUDY SELECTION: Antiviral activity data were included if widely accepted methodology was used. All clinical data currently available from human studies were also included. DATA SYNTHESIS: Cidofovir is similar to ganciclovir in mechanism of action; however, cidofovir does not require viral enzymes for activation. Although the half-life of cidofovir in plasma is only 2.6 hours, the intracellular half-life may be much longer, allowing efficacy with biweekly maintenance dosing. In vitro, cidofovir appears to be equally or more effective than the other agents currently available for the treatment of CMV. In vivo, cidofovir appears to be effective in delaying the progression of CMV retinitis, although no clinical trials to date have directly compared cidofovir with either ganciclovir or foscarnet. Current intravenous dose recommendations are 5 mg/kg once weekly for two doses (induction), and then 5 mg/kg once every other week (maintenance). Since cidofovir is cleared almost entirely by the kidneys, dosage adjustments must be made in patients with impaired renal function. Disadvantages of cidofovir primarily include its risks of adverse drug reactions, such as nephrotoxicity, which is likely to occur in up to 50% of patients if appropriate preventative measures are not taken. Neutropenia and constitutional reactions to probenecid are also commonly encountered during the course of cidofovir therapy. CONCLUSIONS: Cidofovir is the first acyclic phosphonate nucleoside antiviral agent to be approved for general use in the US. In addition to delaying the progression of CMV retinitis, cidofovir may provide some protective benefits to patients at risk for developing the disease and may be active against certain strains of virus resistant to other currently available therapies. Another advantage of cidofovir is its infrequent dosage schedule, which may prove beneficial in patients who are not compliant with daily intravenous dosing regimens. When determining the appropriate treatment for a patient with CMV retinitis, the benefits of using cidofovir must be weighed carefully against the risk of potentially serious adverse effects.