Introduction: Achieving/maintaining effective hormone suppression is fundamental in treating Central Precocious Puberty(CPP). CPP patients are vulnerable to late dosing as they cannot self-administer and require clinic/hospital visits for injections, currently exacerbated by COVID-19. In children, the hypothalamic-pituitary-gonadal axis may rebound faster than elderly oncology patients, so hormone escapes are possible with late dosing. Additionally, the stimulatory flare from GnRH agonists (GnRHa) increases risk of escapes with late injections. Longer duration formulations demonstrating hormone suppression through the dosing interval should be considered. 6-month formulations typically require two office visits/year with only two opportunities to be late. A novel 6-month small-volume, subcutaneously administered GnRHa treatment for CPP approved in 2020 effectively suppressed pubertal hormones and pubertal progression. As large numbers of CPP patients are not present in real-world databases, we present data below in prostate cancer (PCa) patients treated with drugs with the same active ingredient and similar mechanisms of action.
Methods: A retrospective analysis (1/1/07-6/30/16) of US oncology/urology hospitals, multispecialty practices, small group practices, and physician offices EMR of PCa patients receiving GnRHa injections (n = 85,030) was conducted to evaluate the frequency of late injections and testosterone(T) >50/20ng/dL (target levels in PCa). Mean late doses/year for 1,3,4,6-month GnRHa doses were calculated by multiplying late dose proportion and number of doses/year. Late dosing was defined as occurring after days 33,98,129,195, respectively.
Results: 84% of GnRHa were administered later than scheduled. Number of late doses/year for 1,3,4,6-month GnRHa formulations were 5.4,0.8,0.8,0.6 respectively. 27% of T values exceeded 50ng/dL with late dosing compared to only 4% with early/on-time doses. 43% of T values exceeded 20ng/dL for late injections compared to only 21% for early/on-time injections.
Conclusions: 6-month GnRHa formulations require fewer visits for treatment, which will likely be preferred by patients and clinicians, especially during a pandemic. 6-month formulations had fewer late doses/year vs. 1,3,4-month formulations. Late injections in PCa patients were correlated with ineffective T suppression: T levels were >50ng/dL over 25% of the time. Late dosing increased the proportion of T >20ng/dL compared to early/on-time dosing. Clinicians should ensure dosing is on time or consider using 6-month formulations that have less frequent opportunities for late dosing and demonstrate/maintain efficacy through the labeled dosing. This will give greater confidence in continued hormone suppression when late. Similar studies should be conducted to assess the impact of late dosing of GnRHa in CPP patients.
22 Sep 2021 - 26 Sep 2021