From Cost-Benefit Concerns to Personalized Medicine: What's New in Treating the Youngest Patients

Some of the same themes being raised across medicine—how to balance the quality of care with soaring therapy costs, and how to unleash the power of genomics to tailor treatment—were part of Saturday’s workshop “Hot Topics in Pediatric Allergy and Immunology.” The session of the American Academy of Pediatrics took place during the 2014 Annual Meeting of the American Academy of Allergy, Asthma & Immunology in San Diego, California.

Chitra Dinakar, MD, professor of pediatrics at the University of Missouri-Kansas City, and a physician at Children’s Mercy Hospital, included some eye-opening observations about the cost and benefits of prevention efforts involving preterm infants, as part of her review of recent studies of involving pediatric respiratory allergies.

A study from Finland examined the effects of supplementing the diets of preterm infants with prebiotics and probiotics; the first are nondigestible carbohydrates that act as “food” for the probiotics, which in turn may help ward off harmful bacteria in these fragile patients. Use of supplements would appear to be a cost-effective way to prevent respiratory tract infections (RTIs) before they occur.

The study, published in October 2013, found a much lower incidence of RTIs among infants receiving the prebiotics (rate ratio [RR] = .24, 95% confidence interval [CI] 0.12-0.49; P <.001) or probiotics (RR = .50, 95% CI, 0.28-0.98; P = .51) compared with a placebo.¹ The incidence of rhinovirus was also reduced among the group receiving treatment compared with that receiving a placebo. The infants’ protection from RTIs seemed to extend throughout the first 12 months after treatment, Dr Dinakar noted.

Unlike the Finish group’s relatively inexpensive use of supplements, Dr Dinakar said a study and accompanying editorial in Pediatrics discussed whether the use of palivizumab in preventing wheezing in preterm infants is cost-effective. Results of a study involving 349 infants who received palivizumab for 6 months and 95 who did not were published in November; wheezing was reduced significantly, and the benefit appeared to last until age 3.²

As Dr Dinakar observed, the accompanying editorial questioned whether the cost could be justified.³ “When they did the analysis, the acquisition cost (of the therapy) is $200,000 just to save $8000 in hospitalization costs,” she said. “When you look at it that way, it was not that beneficial.”

Genomic Testing of Infants Saves Lives

Thomas A. Fleisher, MD, senior investigator at the National Institutes of Health Clinical Center, discussed promising improvements in genomic screening that are leading to earlier and better treatments of immunologic disorders, including those caught early in newborns as a result of screening done at birth.

Dr Fleisher discussed an assay of T-cell receptor excision circles (TREC), based on work in California, which initiated newborn screening for severe combined immunodeficiency (SCID) in 2010.

Dr Fleisher said the results, published in July 2013, offer a glimpse of what could happen as this kind of screening becomes widely available.⁴ Of nearly 1 million infants screened, 50 had significant T-cell lymphopenia; 15 required hematopoietic cell or thymus transplantation or gene therapy. At the time of the study’s publication, the survival rate of this group was 93%.

What’s more, the TREC test specificity was excellent, only 0.08% of infants required a second test, with 0.16% requiring lymphocyte phenotyping by using flow cytometry.⁴

Having this information guides families and physicians, and it saves lives, he said. Infants who test positive for SCID, for example, do not receive the vaccine for rotavirus, based on a June 2011 advisory from the Centers for Disease Control and Prevention. Even before the announcement, Merck and GlaxoSmithKline, the makers of the RotaTeq and Rotarix, respectively, updated their labeling with approval from the US Food and Drug Administration to reflect the contraindication.⁵

“This shows that screening newborns is working,” Dr Fleisher said of the California results. “Eighteen states now have routine screening for T-cell immunodeficiency,” which covers more than 50% of the infants born in the United States. As time goes on and data accumulate, he said, “We will understand more about the TREC results.”

Genomics will be “front and center” over the next 10 years, he said. Dr Fleisher was among the speakers of the day who said a $1000 price tag to map an individual genome was “not far away.”

The use of genomics for personalized—and especially preventative&mdash;medicine will only increase. “There are 250 genes associated with immunology disorders and that number will grow,” Dr Fleisher said. For all the excitement, however, he cautioned that there are ethical concerns about storage and access of the information that must be addressed, in addition to the question of how much information is extracted about a newborn who has no say in how much information is gleaned from his or her genome.

References

1. Luoto R, Ruuskanen O, Waris M, Kalliomaki M, Salminen S, Isolauri E. Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2013;S0091-6749(13):1307-1309.
2. Yoshihara S, Kusuda S, Mochizuki H et al. Effect of palivizumab prophylaxis on subsequent recurring wheezing in preterm infants. Pediatrics. 2013;132(5):811-818.
3. Meissner HC, Kimberlin DW. RSV immunoprophylaxis: does the benefit justify the cost? Pediatrics 2013;132(5):915-918.
4. Kwan A, Church JA, Cowan MJ et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California: results of the first 2 years. J Allergy Clin Immunol. 2013;132(1):140-150.
5. Martin BN. Rotavirus vaccine contraindicated in infants with severe combined immunodeficiency. Medscape. http://www.medscape.com/viewarticle/723369 Published June 11, 2010. Accessed March 2, 2014.