# Persistence with daily growth hormone among children and adolescents with growth hormone deficiency in Japan

## TL;DR

This study examines how children in Japan stick to daily growth hormone treatment, finding that while most start well, many stop over time.

## Contribution

The study provides real-world data on growth hormone treatment persistence and discontinuation in Japanese children with growth hormone deficiency.

## Key findings

- High early persistence was observed, with over 80% of children refilling their initial growth hormone prescription.
- Using a 90-day gap definition, 35% in one database and 54% in another discontinued treatment by 48 months.
- Few predictors of discontinuation were identified, suggesting a need for new strategies to improve long-term adherence.

## Abstract

Pediatric growth hormone deficiency (pGHD) is treated with daily somatropin (recombinant human growth hormone) injections. High rates of discontinuation and poor adherence to treatment, which are associated with worse growth outcomes, have been documented previously, for example in the US and Europe. Discontinuation of somatropin has not yet been evaluated using real-world data in Japan.

To describe discontinuation of, and persistence to, daily somatropin treatment among children with pGHD in Japan.

This was a retrospective cohort study of children (≥3 and <16 years old) who were prescribed somatropin, using 2 Japan-based databases, Japan Medical Data Center (JMDC) and Medical Data Vision (MDV). Children were required to have ≥1 prescription for somatropin (first prescription = index date) within each study period (1 January 2002–30 September 2021 for JMDC and 1 January 2009–31 October 2021 for MDV) and ≥1 GHD diagnosis code without a somatropin prescription during the 6-months pre-index period. Children were required to be continuously enrolled in the database ≥6 months preceding and ≥3 months following index date. Children were followed for up to 48 months post-index.

Early persistence was defined as the proportion of children with ≥1 refill of somatropin subsequent to the initial prescription. Discontinuation was defined as the first observation of a gap in therapy (using >60, > 90, and 120-day gap thresholds) between successive somatropin prescription fill dates. Persistence was defined as continuous refills of somatropin with no gaps in therapy. Time to discontinuation/non-persistence was evaluated using Kaplan-Meier methods, and Cox proportional hazards models identified predictors of time to discontinuation.

This analysis utilized de-identified patient data from 2 large, Japanese-based retrospective databases; as such this study does not meet the requirements for institutional review board (IRB) review.

Among the children included in this study (JMDC N = 452, MDV N = 573), most were male (JMDC 64.8%, MDV 60.0%). Mean age (standard deviation) was 8.8 (3.6) years in JMDC and 7.5 (3.6) years in MDV. Early persistence was high across both cohorts (JMDC 91.2%, MDV 83.4%). Using the 90-day gap definition for discontinuation, a sizable proportion of children discontinued over the follow-up period: JMDC 19% at 12 months, 35% at 48 months; and MDV 33% at 12 months, 54% at 48 months. Fewer discontinuations were observed with the 120-day gap definition (~16% at 48 months in JMDC, ~ 28% at 48 months in MDV) and more were observed with the 60-day gap definition (~67% at 48 months in JMDC, ~ 83% at 48 months in MDV). No meaningful predictors of discontinuation were identified.

Despite high early persistence with somatropin, many children with pGHD in Japan were increasingly non-persistent over time: at 48 months post-index, at least 16% of children discontinued therapy, using the JDMC database and the most conservative measure of gap allowance. These results suggest a need for new strategies to support somatropin medication use over time among children with pGHD in Japan.