Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Idiopathic Short Stature
Treatment: Nutropin AQ
The insurer denied the Nutropin AQ.
The denial is overturned.

The patient is a male with the diagnosis of non growth hormone deficiency short stature based on a height at -2.45 normal bone age, growth velocity of 2.64 cm/yr (centimeters per year) or -5.4 SDS (standard deviation score), normal growth hormone stimulation test of 11.3 ng/dL (nanograms per deciliter) with an IGF-1 (insulin-like growth factor 1) of -1.1 SDS, patient has a height prediction of 159.70 cm or 62.8 inches.

Yes, the proposed treatment is medically necessary.

This patient has the diagnosis of idiopathic short stature (ISS). In the United States of America, children who meet FDA (Food and Drug Administration) criteria are considered candidates for GH (growth hormone) treatment based on studies that have shown GH treatment increases the mean height of treated cohorts. Growth hormone in the treatment of ISS is supported by randomized controlled trials and consensus guidelines. FDA approval for this indication is for "non-growth hormone deficient short stature, defined by height SDS less than or equal to -2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range < (greater than) 63 inches in boys, in pediatric patients whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means." This patient did have a pretreatment height less than or equal to -2.25 SDS, meeting the diagnosis of ISS criteria, his initial height was at -2.64 SDS with an extreme growth velocity and a height prediction that is less than 63 inches. These values were also suggested in a consensus statement from the Growth Hormone Research Society, Pediatric Endocrine Society (PES), and the European Society for Pediatric Endocrinology (ESPE). GH in the treatment of ISS is supported by randomized controlled trials and consensus guidelines.

There is enough data that suggests that patients with these characteristics are good candidates for treatment. In a recent study by Seul Ah Kim, et al, 12 patients in the ISS group who had a height SDS of -2.2 showed that GH treatment had a height gain after 1 year of growth hormone treatment of 7.68 (plus or minus) 1.44 cm. Similarly, in Ross, et al, ISS (n=733) with baseline height (H) SDS-2 were assessed over 5 years of growth hormone treatment, had a HSDS (height standard deviation score) at year 5 of 1.6, showing that Long-term growth hormone therapy resulted in a significant increase in mean HSDS and corrected HSDS from baseline values in ISS.

Another study by Counts, et al showed that in a 4-year, open-label, multicenter, randomized trial in prepubertal stage, had a bone age of 3-10 years for males and a HSDS of -3 to -2.25, a height velocity < (less than) 25th percentile for their bone age, and peak stimulated GH > 10 ng/ml (nanograms per milliliter). At 4 years, ISS subjects had an average height gain of +1.3 SDS.

Another study by Sotos, et al showed that in 123 children with ISS HSDS of -2 treated with rhGH (recombinant human growth hormone), 88 of the children (68 males and 20 females) attained an adult height or near adult height of -0.71 SDS (0.74 SD) with a benefit over untreated controls of 9.5 cm (7.4 to 11.6 cm) for males.

Another study by Kristrom B., et al that included non-GH deficiency children with height below 2 SDS chronological age 10-15 years for boys showed that GH treatment resulted in greater HSDS change than in the control group (1.1  0.84 vs 0.4  0.85).

In a meta-analysis by Finkelstein, et al which included patients with ISS: initial height below the 10th percentile, normal stimulated GH levels (> 10 microgram/liter), absence of comorbid conditions showed that 1-year growth velocity of the GH-treated group significantly exceeded that of controls by 2.86 cm/yr. Similarly, in uncontrolled trials, growth velocity increased after 1 year, and HSDS increased from -2.72 at baseline to -2.19. In controlled studies, the adult height of the GH-treated group significantly exceeded controls by 0.84 SD, and in uncontrolled trials the adult height attained after GH treatment (-1.62 SD) exceeded that predicted at baseline (-2.18 SD). Thus, the literature shows that the use of GH therapy promotes growth in children with ISS.

No, the health plan did not act reasonably, with sound medical judgment, or in
the best interest of the patient.