Persistence of Use in Children Receiving Growth Hormone Therapy

Abstract

Abstract Background: Long-term persistence of use and starting at the earliest possible age are associated with attainment of near-normal adult or final height in children who are treated with growth hormone therapy. However, there are many factors associated with a lack of persistence. Our aim was to study persistence of use in children with growth disorders using the easypod™ connected autoinjector e-device, which automatically records adherence data and can transmit them via an online portal (easypod™ connect). We investigated persistence of use, defined indicators of a long persistence of use, and developed a model to predict and identify children at risk of discontinuing treatment in the following 6 months. Data and Methods: Anonymized data from children transmitting over 10 injections between January 2007 and April 2020 were analyzed. A child was considered to discontinue the use if they had no injection in the last 6 months (before April 2020) or had an injection pause of at least 6 consecutive months. Persistence was estimated by Kaplan-Meier analyses and Weibull accelerated failure time modeling. To predict the individual risk of discontinuing the use in the following 6 months, individual survival probabilities curves were estimated for each patient still using the system, and the survival probabilities were then recalculated such that they were conditional on the fact that a child had already used the device for a certain time. The Harrell’s c-index was used to assess the algorithm performance. Results: Data were available for 17,651 children of whom 11,056 discontinued the use and 6,595 were still persistent in April 2020. Median persistence of use for all patients using the device was 2.1 years. There was a highly significant difference in median persistence of use between the regions: 1.0, 1.5 and 2.8 years in the available countries in the Asia-Pacific, America and Europe regions, respectively. Other indicators that had a significant positive impact on persistence of use were: at least one dose change a year, having auxological measurements recorded in the system (and if ‘Yes’, height standard deviation < -2 at start of use had an additional effect), starting treatment at an early age, adherence ≥85%, customized injection speed setting and being male. For the individual prediction, random survival forests showed the best performance (Harrell’s c-index=0.72). Conclusions: Data from the connected autoinjector e-device showed that the persistence of use was approximately 2 years in children with growth disorders. We were able to define 8 indicators that had a positive impact on persistence of use of which several indicators were related to patient management. Our prediction model can be used to identify children needing support to reach longer persistence of use and subsequently optimal clinical outcomes.