RSV-IGIV Therapy: A Cost/Benefit Analysis

To the Editor. RSV-IGIV (RespiGam, MedImmune Inc, Gaithersburg, MD 20878, USA) was approved by the Food and Drug Administration in 1996, and recently endorsed by the American Academy of Pediatrics for prophylaxis against respiratory syncytial virus (RSV) infection in children under 24 months of age with history of bronchopulmonary dysplasia or premature birth (35 weeks or less). In the current environment of cost-consciousness, the drug's high cost, modest clinical efficacy, and potential for serious adverse reactions are critical concerns.Based on a cost of $699.50 per 2.5-g RespiGam vial and $234.50 per intravenous infusion charges (“cost to the patient” as charged in a large, urban teaching hospital), we calculated that RSV-IGIV therapy at a dose of 750 mg/kg/infusion per month through the RSV season (November through April) for a 3.3-kg, 6.6-kg, and 10.0-kg infant would cost $5604, $9801, and $13 998, respectively. A cost analysis of RSV-IGIV therapy, based on RespiGam efficacy data from the PREVENT trial,1 is shown in the Table. The estimated cost of RespiGam therapy for a 6.6-kg infant for preventing: a) one RSV admission is $179 505; b) one RSV hospital day is $14 204; and c) one RSV hospital day with supplemental oxygen is $19 218. These calculations do not account for the following additional costs: charge for the hospital room, oxygen saturation monitoring and other skilled nursing services, attending physician's services, therapy for RSV-IGIV infusion-related complications, screening for IgA deficiency, and additional doses of DTP, DTaP, Hib, OPV, and MMR vaccines. Thus, in many cases, the actual cost to the patient for the RSV-IGIV infusion therapy may be much higher than those shown in the Table. Previously, Hay et al2 had calculated that RSV-IGIV prophylaxis for all eligible high-risk children in the United States would reduce RSV-related medical cost from $628 million to $178 million (a savings of $450 million) but the RSV-IGIV therapy per se would cost $1.871 billion annually!Despite its high cost, does RSV-IGIV therapy save lives or prevent serious complications? The PREVENT Trial1 did not show a statistically significant difference between the control and the RSV-IGIV groups on the following outcomes: 1) RSV-related ICU admission rate, 2) RSV-related intensive care unit days per 100 children, 3) RSV-related mechanical ventilation per 100 children, and 4) RSV-related ventilator days per 100 children. The Cardiac Trial3 had failed to show benefit from RSV-IGIV therapy in the children with congenital heart diseases. Further, RSV-IGIV therapy has not been shown to be effective for treatment of RSV infection3 nor to reduce RSV-related mortality.134 Similarly, prophylactic or therapeutic efficacy of RSV-IGIV in immunocompromised children or against nosocomial RSV infection in hospitalized high-risk infants remains to be proven. This limited clinical benefit from passively transfused antibodies is not surprising in view of recent evidence implicating significant roles for cell-mediated immune responses5 as well as cytokines6 in host defense against RSV infection.RSV-IGIV has a potential for adverse reactions134 such as fluid overload, decreased oxygen saturation, and respiratory failure requiring mechanical ventilation. In the RSV-IGIV trials,14 11 children died in the RespiGam group. Although the authors did not attribute the deaths to RSV-IGIV therapy, it is notable that there were only two deaths in the control groups.1 Immunoglobulin infusions may also result in aseptic meningitis syndrome, anaphylactic reaction in an IgA-deficient person, transmission of serious infections such as hepatitis C, and interference with immune response to MMR vaccine.Therefore, based on currently available data for safety, efficacy, and cost, one must seriously question if RSV-IGIV therapy is really cost-effective.In Reply. Thakur et al superficially cover a number of different topics regarding RSV-IGIV (such as lack of efficacy in treatment, lack of data for immunocompromised patients, and guidelines for noscomial disease). This has nothing to do with the current published recommendations of the Food and Drug Administration or the American Academy of Pediatrics. They also include costs that are not necessary (such as the need to test for IgA deficiency before use). Also, there is misinformation such as the need to repeat all immunizations with RespiGam.Hay et al1-1 in their cost analyses factored in all of those items that are only vaguely alluded to at the end of the second paragraph of the letter by Thakur et al. The last sentence of this paragraph is pretty far-fetched. I would not call RSV-IGIV of “limited clinical benefit” and his tie-in with the immune response is too loose.The most important point, however, is that the cost-benefit analyses are currently based on cost per year of life saved. When evaluated from this perspective, RSV-IGV is cost-effective.1-1To summarize, the aforementioned letter is not carefully researched and it is too simplistic. It reads more like a “smear campaign” rather than as a well-thought-out editorial.