AAP updates guidance on palivizumab prophylaxis for RSV

Leonard R. Krilov, MD, FAAP, FIDSA

These guidelines recommend drastically greater restrictions on palivizumab use than prior guidelines. Although in prior statements the COID has emphasized cost considerations in developing their recommendations, this statement emphasizes the limited clinical benefit from palivizumab instead of cost. Specifically three factors are cited to support this contention: palivizumab has limited effect on RSV hospitalizations on a population basis; no measurable effect on mortality has been demonstrated in palivizumab recipients; and only a minimal impact on subsequent wheezing has been demonstrated.

Regarding the final two points, it should be noted that a decrease in mortality with palivizumab has never been demonstrated. The decrease in the hospitalization rates and the decrease in severity of illness even when hospitalized are the primary benefits observed.

The impact of prophylaxis on subsequent wheezing has never been part of the recommendations and is just beginning to be elucidated. Blanken et al recently reported a 61% reduction in wheezing days over one year in a group of premature infants receiving prophylaxis compared to controls. If this is sustained and verified in other populations from a clinical and cost perspective, there would be more than a minimal benefit. It could be a very significant potential benefit.

The guidelines cite lower hospitalization rates than were seen in the clinical trials leading to FDA approval in 1998, which diminishes the potential benefits of palivizumab. Subsequent data also demonstrate a significant impact on preventing medically attended RSV infections in prophylaxed infants, which may offset some of this effect.

Additionally, the epidemiology studies in the technical report which suggest lower RSV-related hospitalization rates compared to those seen in the pivotal IMpact Trial, particularly among premature infants of more than 29 week gestational age, have limitations. Two of the studies come from the same network and, as noted by the authors, they may not be representative of the entire United States. Furthermore, palivizumab was used during the study period and it is not clear whether this impacted hospitalization rates for the high-risk infants and the number of premature infants included is small. In the Boyce study, a two-fold increase in hospitalization rates was seen up to 6 months chronological age for infants less than 33 weeks gestational age. This is 1.8 times higher for those born at 33 to 36 weeks gestational age.

As for the limited impact of palivizumab in decreasing RSV hospitalizations on a population basis, it is true in large part because these high-risk infants are a very limited part of the population. Thus, even under prior guidelines palivizumab is also only indicated for this very limited population.

Hopefully in the near future availability of a RSV vaccine will change the landscape and preclude, or at least diminish, the need for palivizumab prophylaxis. Until such time, palivizumab is the only available option for protection of high-risk infants. In the absence of more definitive data to help optimize the indication for prophylaxis I believe further discussion among all experts involved in the care of infants at high-risk for severe RSV disease is needed before the 2015 guidelines are adopted.