Yearly Height Gain Is Dependent on the Truly Received Dose of Growth Hormone and the Duration of Periods of Poor Adherence: Practical Lessons From the French Easypod™ Connect Multicenter Observational Study.

Receiving a mean daily dose below 0.03 mg/kg/day with fewer than 3 injections per week over 12-month periods was associated with a 20% lower mean yearly height gain SDS compared to receiving more than 5 injections per week.

• The comparison was made between patients receiving <3 injections/week vs. >5 injections/week at a mean daily dose <0.03 mg/kg/day.
• The 20% lower yearly height gain SDS was observed when both the dose and injection frequency were low over 12-month periods.
• Maintaining a mean daily dose >0.03 mg/kg/day with <3 injections/week was NOT associated with a lower yearly height gain SDS compared to >5 injections/week.
• Linear mixed models were used to study the impact of variations in rhGH administration on yearly height change as SDS, with time on treatment as a covariate.

Changes in daily rhGH dose or number of injections per week over short 3-month periods did not influence the yearly height gain SDS.

• For 3-month periods, neither changes in daily rhGH dose nor number of injections per week impacted yearly height gain SDS.
• This finding suggests that poor adherence for short periods (<3 months) had no impact on height SDS.
• The analysis used a 3-month treatment model examining short-term periods of poor adherence designated as either poorly adherent or fully adherent.

The study enrolled 220 children from the French Easypod Connect Observational Study (ECOS) who used the Easypod electronic device to record rhGH injections.

• At treatment initiation, the mean ± SD age was 9.8 ± 3.7 years; 47% were female and 86% were prepubertal.
• The mean height at treatment initiation was -2.28 ± 0.92 SDS.
• The mean treatment duration was 3.2 ± 1.1 years, totaling 685.2 patient years.
• 122 patients were GH-deficient, 79 were small for gestational age, and 19 had Turner syndrome.

The true mean daily dose was calculated as the sum of doses truly received divided by the number of days, and the true mean number of injections per week was the number of injections truly performed divided by the number of weeks.

• The Easypod electronic device recorded actual rhGH injections, allowing calculation of truly received doses rather than prescribed doses.
• For each patient, several periods of 3 or 12 months were considered and designated as periods of poor adherence or full adherence.
• This methodology distinguished between prescribed and actually received doses, enabling assessment of true adherence impact on growth.

The key determinant of yearly height gain was the true mean daily dose received over 12-month periods, with injection frequency only mattering when it resulted in a reduced total daily dose.

• When daily dose was maintained above 0.03 mg/kg/day despite fewer injections per week, height gain was not compromised.
• The 12-month treatment model showed that poor adherence only affected yearly height gain when it led to a low true daily GH dose.
• The interaction between dose and injection frequency indicates that compensatory dosing on injection days may preserve overall exposure and growth outcomes.