Is Selective Use of Palivizumab Appropriate in Premature Infants?
Is Selective Use of Palivizumab Appropriate in Premature Infants?
MANAGED CARE September 2003. ©MediMedia USA
In reference to the article in the May 2003 issue of Managed Care entitled "A Health Care Management Company's Experience with Palivizumab," the assertions made by William Silverman, MD, in that article deserve comment.
The article indicates that Horizon/Mercy denied palivizumab immunoprophylaxis for 152 infants who qualified for such prophylaxis according to the American Academy of Pediatrics (AAP) guidelines, and for whom the request for coverage was made by the children's physicians. Dr. Silverman's post hoc conclusion seems to be that, inasmuch as no respiratory syncytial virus (RSV) hospitalizations occurred among this group of infants, the decision to deny prophylaxis was the "appropriate decision." Dr. Silverman implies that if a health plan denies a costly but effective preventive intervention deemed reasonably appropriate by both the AAP and the physicians caring for the plan's patients, then the denial is justified so long as no adverse outcomes occur.
Using a similar argument, a health plan might well deny other preventive measures for children — such as immunizations against pneumococcus, diphtheria, tetanus, pertussis, polio, varicella, measles, mumps, or rubella — for which preventive care is considered standard. If no adverse outcomes occurred — which would likely be the case — then the decision to deny the service would be considered "appropriate." This cost-driven approach seems a far cry from evidence-based medicine, a paradigm that is embraced by both physicians and managed care. This approach described here is akin to "gambling-based medicine."
A large scale, population-based analysis of Medicaid administrative data in Tennessee found that 33- to 35-week gestational age infants face elevated rates of RSV hospitalization similar to those of infants born at younger (¾32 weeks) gestational ages (Boyce 2000). Importantly, published data from a large clinical trial showed that RSV hospitalization rates were reduced by 80 percent among 32- to 35-week gestational age infants who received palivizumab compared with a placebo group (Impact-RSV Study Group 1998).
Data from the same geographic area in which Horizon/Mercy operates raise additional questions about Dr. Silverman's conclusions. My colleagues and I examined the severity of RSV infection in hospitalized premature infants, looking specifically at the effect of gestational age.
Understanding that some controversy remains as to whether premature infants of 32 to 35 weeks' gestation should routinely or selectively receive immune prophylaxis, we set out to compare the severity of illness of infants of different gestational ages who were hospitalized with RSV infection and who did and did not receive palivizumab prophylaxis. Our study design consisted of a retrospective chart review of 1,074 infants of <2 years of age, admitted to nine hospitals in the Delaware Valley with confirmed RSV infection during the 10/1/98 to 4/30/99 season. Once hospitalized, the severity of respiratory illness was similar in the two groups of nonimmunoprophylaxed premature infants, regardless of their gestational age (<32 weeks and 32 to 35 weeks) (Table 1).
|GA (wk)||N||LOS||O2 (%)||Ventilation||ICU (%)|
|LOS = length of stay; GA= gestational age. Results presented as mean and percentage.|
Despite the small sample size, none of the immunoprophylaxed premature infants required mechanical ventilation, and they had a shorter length of hospital stay. Our data suggest that palivizumab prophylaxis is beneficial for premature infants of 32 to 35 weeks' gestation, who were hospitalized for the treatment of RSV infection. This work was presented in a highly respected, peer-reviewed forum — the Pediatric Academic Societies Annual Meeting, held in Baltimore, April 27, 2001 through May 1, 2001. MedImmune Inc. supported the costs of data collection and analysis.
In a more recent large-scale Canadian study that was presented as a late-breaking abstract at the Pediatric Academic Societies Annual Meeting in Seattle, which took place from May 3, 2003 through May 6, 2003, Sampalis evaluated the impact of RSV-associated hospitalization on subsequent use of hospital services and mortality in healthy preterm infants born between 32 and 35 weeks' gestational age. This case-controlled study examined the experiences of 2,415 unprophylaxed cases of RSV-associated hospitalizations, [in infants] born between 1998 and 2001, who were matched to 20,254 controls who were not hospitalized. The mean follow-up was 1.66 years, and infants with congenital abnormalities and bronchopulmonary dysplasia were excluded.
The results of the study revealed a statistically significant (P=.001) increase in hospitalization, special care unit visits, respiratory therapy visits, MD consults, in-hospital procedures, outpatient visits, and total in-patient days for the cases as compared to the controls. A combination of increased use of hospital resources and recent acquired knowledge on the long-term consequences of RSV infection due to an initial RSV infection adds to the cost of these patients. Of great concern is the more than 20-fold increase in the risk of SIDS in the case group of healthy 32- to 35-week gestational age infants as compared to the nonhospitalized control group.
Given the seasonal variability of RSV severity, as documented by the Centers for Disease Control «www.cdc.gov/ncidod/dvrd/revb/nrevss/rsvtre1.htm», published hospitalization rates among 32- to 35-week gestational age infants, our data pertaining to severity of illness among 32- to 35-week gestational age infants hospitalized in the Delaware Valley, and the increased use of health care resources and the associated greater risk of sudden infant deaths in the Canadian study as a result of RSV infection, Dr. Silverman's policies can only serve to harm children at risk; it is just a matter of time.
Sonia Imaizumi, MD
Associate Director, Neonatal Services
The Children's Regional Hospital
The Cooper Health System
Chair Elect, Home Health Care Section
American Academy of Pediatrics
Boyce TG, Mellen BG, Mitchel EF, et al. Rates of hospitalization for respiratory syncytial virus infection among children in Medicaid. J Pediatr. 2000;137:865-870.
Impact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics. 1998;102:531-537.
Imaizumi S, Agarwal S, Pereira G. Severity of respiratory syncytial virus (RSV) infection in hospitalized premature infants: the effect of gestational age and immune prophylaxed with palivizumab. 2001 APS/SPR/APA Annual Meeting, Baltimore, Md.
Sampalis J. Morbidity and mortality following RSV associated hospitalization among premature Canadian infants. 2003 Pediatric Academic Societies' Annual Meeting, Seattle.
The study's author responds to Dr. Imaizumi's letter regarding his paper on palivizumab, which appeared in the May 2003 issue of Managed Care:
Although Dr. Imaizumi correctly points out that some controversy remains as to whether premature infants of 32 to 35 weeks' gestation should routinely or selectively receive immune prophylaxes with palivizumab, the studies that she goes on to quote do not specify which risk factors were present in the infants of 32 to 35 weeks' gestational age.
Two distinct groups of risk factors are involved in RSV infection. One group (cyanotic congenital heart disease, chronic lung disease, immunodeficiency disease, severe neuromuscular disease, and significant congenital abnormalities of the airways) increases the severity of RSV disease. The other group of risk factors that increases the chances of acquiring RSV infection is the one addressed in our articles (Silverman 2002, Silverman 2003). Again, bear in mind that one can acquire RSV infection and end up with a runny nose. The risk factors that I label as environmental risk factors may increase the incidence of acquiring RSV infections, but there is no evidence in the literature that these factors increase the severity of RSV infection. These environmental risk factors, such as smoking in the household, child-care attendance, and school-aged siblings were not derived from "evidenced-based medicine," and Dr. Imaizumi, in the studies that she quoted in her letter, does not specify or single out any risk factors.
In the 2003 Red Book, the recommendations for the use of palivizumab have been updated. Some of these significant changes are as follows: exposure to tobacco smoke is a risk factor that can be controlled by the family of an infant at increased risk of RSV disease, and preventive measures will be far less costly than palivizumab prophylaxis. High-risk infants should never be exposed to tobacco smoke; high-risk infants should be kept away from crowds and from situations in which exposure to infected individuals cannot be controlled; participation in child care should be restricted during the RSV season for high-risk
infants, whenever feasible.
There are other recommendations concerned with the use of palivizumab in hemodynamically significant congenital heart disease rather than in hemodynamically insignificant heart disease.
I feel that the changes in the 2003 Red Book recommendations support the conclusions that I came to in my article.
William Silverman, MD, FAAP
American Academy of Pediatrics. 2003 Red Book: Report of the Committee of Infectious Diseases. 26th edition: pp. 523-528.
Silverman W. A healthcare management company's experience with palivizumab. Manag Care. 2002:11(1);45-46.
Silverman W. A healthcare management company's experience with palivizumab - 1 year later. Manag Care. 2003:12(5);49-50.
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