On June 19, 1998, the Food and Drug Administration licensed palivizumab, as the first monoclonal antibody introduced into clinical practice for the prevention of an infectious disease, respiratory syncytial virus (RSV) disease. In the November 1998 issue of Pediatrics, the American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and the Newborn published guidelines for the use of palivizumab.1
Horizon/Mercy, a health care management company jointly owned by Horizon HMO of New Jersey and Sisters of Mercy of Pennsylvania, currently has approximately 235,000 members.
The membership of this health maintenance organization exclusively comprises publicly insured enrollees, including those enrolled in Medicaid and NJFamilyCare (SCHIP:State Children's Health Insurance Program).
Enrollees include about 6,000 newborns a year. Of these, 1.4 percent are under 32 weeks' gestation and 2.9 percent are between 32 and 35 weeks gestation.
The investigators for this study reviewed the data on palivizumab following its second season of use, which was between Oct. 1, 2000 and April 30, 2001.
When making a determination as to the approval of palivizumab, our medical directors consider the recommendations of the American Academy of Pediatrics. After a review of the literature on the subject, however, our group determined that it would be best not to approve palivizumab if the only risk factors mentioned were considered "additional risk factors" (See below table.).
|Additional risk factors for RSV infection|
|Reported additional risk factors for RSV infection||Number of patients*|
|Exposure to tobacco smoke in the home||16|
|Crowding in the home||7|
|On apnea monitor for apnea of prematurity||9|
|History of apnea — off monitor||2|
|History of reactive airway disease ||9|
|History of respiratory distress syndrome ||9|
|History of RSV in previous season||1|
|31 weeks' gestation without chronic lung disease (CLD), more than 6 months of age at start of RSV season||1|
|Full term with PDA†; no CLD||1|
|Full term with laryngotracheomalacia||2|
|34 weeks' gestation, history of bronchopulmonary dysplasia (BPD); no treatment for more than 6 months||1|
|36 weeks' gestation; gastroesophageal reflux disease; no CLD||1|
|24 weeks' gestation; history of BPD; no therapy for 9 months; 15 months old at start of season||1|
|36 weeks' gestation; small for gestational age||1|
|33 weeks' gestation; as newborn, required oxygen for 3 days||1|
|*Total number exceeds 79 patients, because some patients had >1 factor.|
†PDA = Patent ductus arteriosus (a form of acyanotic congenital heart disease: the connection between pulmonary artery and aorta present during fetal life that should close shortly after birth, as the circulation changes).
Our group approved those requests if the children had any of the following risk factors:
- Children under 2 years of age who have chronic lung disease and who require medical therapy for their disease in the 6 months prior to the RSV season.
- Infants born under 29 weeks' gestational age, who are less than 12 months old at the onset of the RSV season.
- Infants born under 29 weeks' gestational age, who have chronic lung disease and are less than 24 months of age at the onset of the RSV season.
- Infants born between 29 and 32 weeks' gestational age, and who are less than 6 months of age at the onset of the RSV season.
- Infants born between 32 and 35 weeks' gestational age, if they have other risk factors, such as severe immunodeficiency (SCIDS or AIDS) or acyanotic, asymptomatic congenital heart disease.
During the 2000–2001 RSV season, we approved 212 requests for palivizumab. 12 of these members, 5.7 percent, required hospitalization for proven RSV lower respiratory tract disease, either RSV bronchiolitis (ICD-9 code 466.11) or RSV pneumonia (ICD-9 code 480.1). The average length of stay was 4.6 days. These results are consistent with the results of the original randomized clinical trial of palivizumab. In that study, known as the Impact-RSV trial, there was a 55-percent overall reduction in RSV-related hospitalizations (11 percent compared to 5 percent in placebo vs. palivizumab recipients).2
Nevertheless, the big question is: What about the requests that were denied? What about the patients who were between 32 and 35 weeks' gestation whose only risk factors were the "additional risk factors" listed in the accompanying table? In the American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and the Newborn article on RSV infections and indications for the use of palivizumab, there is a section entitled "Costs-Benefit Analysis," and therein, the following statement is made: "For many infants, qualifying for the approved indications, risk of rehospitalization for serious respiratory illness will be low, and the cost and logistical difficulties associated with prophylaxis may outweigh the potential benefits."1
Importantly, of the 79 members for whom the request for palivizumab was denied, none of those members required hospitalization for RSV-related lower respiratory tract illness.
The authors conclude that these results demonstrate that they have made the appropriate decision not to approve palivizumab for the above-mentioned additional risk factors. The importance of this managed care organization's experiences to other managed care organizations is that it demonstrates that, by appropriate application of criteria for the use of palivizumab, a significant amount of money ($6,000 per case, and in this incident, $6,000 multiplied by 79 cases, which equals $474,000) can be saved while at the same time demonstrating no additional risk to the patient. The investigators therefore have determined that the issue of these additional risk factors should be revisited. Hopefully, other managed care organizations and other medical institutions will supply data that will be helpful in making a decision on this matter.
- American Academy of Pediatrics Committee on Infectious Diseases. Prevention of respiratory syncytial virus infections: Indications for the use of palivizumab and update on the use of RSV-IGIV. Pediatrics. 1998;102:1211–1216.
- The 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.
William Silverman, MD, FAAP
275 Phillips Boulevard
Trenton, N.J. 08618