Persistence With Growth Hormone Therapy in Pediatric Patients | Page 3

Published Online: February 19, 2014
Bradley S. Miller, MD, PhD; Deborah Rotenstein, MD; Larry C. Deeb, MD; John Germak, MD; and Tami Wisniewski, MPH
The mean corrected HSDS in the combined IGHD and MPHD groups also increased significantly from baseline to the year 3 visit (Table 3) in patients in all categories (Figure 2B, P <.0001). Pairwise comparisons showed that mean corrected HSDS at last visit for patients who discontinued due to final height achieved (−0.3 ± 0.98, n = 258) was significantly higher than the mean corrected HSDS for other (−1.0 ± 1.07, n = 139; P <.0001), insurance issues (−0.9 ± 1.03, n = 190; P <.0001), and patient and caregiver decision (−0.5 ± 1.18, n = 110; P = .05). Mean corrected HSDS for final height achieved at year 3 (−0.3 ± 0.90, n = 179) was significantly higher than that for other (−1.0 ± 1.03, n = 55; P = .0006) and insurance issues (−0.6 ± 0.81, n = 63; P = .0269), but it was not significantly higher than that for patient and caregiver decision (−0.5 ± 1.07, n = 39; P = .23).

A higher percentage of children in the fi nal-heightachieved discontinuation category reached HSDS greater than −2 at year 3 (96.4%) compared with children in the other 3 discontinuation categories: patient and caregiver decision (94.1%), insurance issues (88.6%), and other (78.5%). Annualized growth rates for the 6 to 12 months prior to discontinuation showed that children who discontinued due to final height achieved had the lowest HV (3.4 ± 2.06 cm/y, n = 249) compared with children in the other categories (Table 3); this is consistent with children in the final-height-achieved group approaching their fi nal height and fusion of their epiphyseal growth plates.


Persistence and adherence are necessary to ensure that GHD patients who receive GH treatment attain their genetic height potential.8,13 Good adherence to prescribed regimens, including GH therapy, wanes beyond 2 years of treatment.10,13,16,17 Good medication adherence among patients is considered to range from 80% to 95% of prescribed doses taken.16 Objective assessments of poor adherence to GH have included analyses of prescription data; patient/caregiver questionnaires, which were followed up with serial clinical assessments to capture HSDS and HV; and the association between HV SDS and the number of GH vials requested or returned empty.9,11,12 By any measure, outcomes have consistently shown that significantly greater linear growth and attainment of genetic height potential are positively associated with adherence to prescribed GH therapy.9,11,12 Adherence to GH regimens is important, but persistence may be even more critical because gaps in therapy that lead to delayed or missed GH doses over the prescribed duration of time from therapy initiation to discontinuation cause suboptimal response to GH treatment that negatively impacts growth outcomes.8,9,12,13

In the current study, patients who were most persistent with GH therapy (ie, those who reached the category of final height achieved) attained a statistically significant increase in linear growth with a final HSDS of –0.6 compared with –2.1 at baseline. This result is consistent with increasing linear growth patterns to near-adult height in prepubertal children with GHD or MPHD from other large patient registry databases.7,18 Current analyses of data from the ANSWER Program showed that patients who reached final height achieved were the most persistent with GH therapy and achieved a corrected HSDS of −0.3 compared with a baseline corrected HSDS of −1.8; that indicates that these patients, on average, had reached an adult height consistent with their genetic height potential. This result compares favorably with published target adult or genetic HSDS values within normal standards (±0.5) for North American adults and children.13,19 The fact that children in the final-height-achieved group had the slowest HV in the period prior to discontinuation but had the highest percentage in the normal adult height range also provides evidence that final height achieved was the primary reason for discontinuing therapy. Although MPHD patients in the final-height-achieved group had a longer duration of treatment, overall persistence was similar between patients with IGHD or MPHD, regardless of the reason for discontinuation.

The second-most common reason for patients discontinuing GH therapy was insurance issues; patients in this category were less persistent with GH treatment. Although patients discontinuing GH for insurance issues did not achieve height outcomes comparable to those of patients in the other categories, a shorter duration of treatment in this cohort may be a factor in their decreased height outcomes. However, even at the same duration of treatment at year 3, children in the final-height-achieved group attained greater HSDS and corrected HSDS than children in insurance-issues group and the other group; the final-height-achieved group also had the highest percentage of patients reaching an HSDS greater than −2. These results could imply that patients in the insurance-issues and other categories may already have had some adherence challenges related to insurance or other reasons. We were unable to evaluate the long-term effects of interrupted GH therapy in this cohort due to a lack of follow-up data once these patients were discontinued from the registry.

Additionally, although the baseline HSDSs for groups characterized by reason for discontinuation were comparable, there did appear to be differences in the mean age and proportion of males in the insurance-issues group compared with the other 3 groups. For these reasons, it is difficult to conclude that ultimate adult height values would differ among these groups. However, given the younger baseline age and bone age of the insurance-issues group, it might be expected that these patients would have shown a better growth response, which was not the case either at the last visit or after 3 years of treatment.

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Issue: January/February 2014
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