(97) Impact of Risk Minimisation Measures on The Use of High-Dose Cyproterone Acetate in France

Publication Number: 428

Background: In 2018-19, the French health authorities conducted risk minimisation measures (RMMs) to address the risk of meningioma with prolonged use of cyproterone acetate (CPA) (>=25mg/jour), a potent progestogen with antiandrogen activity. At the end of August 2018, new results demonstrating a strong dose-effect relation were communicated to the general public in France and received considerable media coverage. Healthcare professionals (HPs) were asked to review ongoing CPA treatments and to prescribe MRI brain imaging (at CPA initiation, 5 years later and then every 2 years). In June 2019, letters were sent to HPs providing a list of their CPA patients and also to the CPA patients themselves. Both were asked to get in touch and were informed of the new “proof of information form” to be signed yearly and required for filling CPA prescriptions (from January 2020).

Objectives: To assess the RMMs’ impact on prescribing practices using the French national healthcare database (SNDS).

Methods: The monthly numbers of CPA users (prescription filled in month m or m-1) and initiators (365-day washout) per sex were calculated between January 2010 and June 2021, as well as the monthly proportion of patients with MRI brain imaging in the preceding 5 years, both among CPA users and initiators. Interrupted time series analyses were conducted and switches (within 1 year) were analysed.

Results: After a continuous decrease in CPA use from 2010 onwards, there was a sharp drop after 08/2018, accelerating further after 06/2019, but then easing after 12/2019: for women, totals were 72,923 (01/2010), 46,726 (08/2018), 9,105 (12/2019) and 5,983 (06/2021) and for men 12,784, 7,839, 3,337 and 2,586, resp.. The number of female and male CPA initiators decreased from 2,154 in 06/2018 to 183 in 06/2021 (-91.5%) and from 676 to 187 (-72.3%), resp.. For women, the proportion of CPA users with MRI brain imaging rose from 10.5% in 06/2018 to 69.2% in 06/2021 (9.8% and 43.7%, resp., in CPA initiators). For men, the proportions were 13.3% and 48.1% (11.4% and 32.1%), resp.. For women, among all CPA stops in the 2 years after 08/2018 , 40.8% were relayed by a drug with ATC code G (e.g. 8.2% by ‘levonorgestrel and ethinylestradiol’, 7.1% by desogestrel, 4.5% by progesterone); for the 2 years before 08/2018, proportions were 36.7% (6.2%, 3.4%, 3.1%), resp.. The proportions of CPA stops relayed by spironolactone were 5.3% and 2.1% after 08/2018 and before, resp..

Conclusions: In France, the use of high-dose CPA decreased sharply after the 2018-2019 RMMs (by 87% in women and 67% in men, until June 2021). No large-scale switches to alternative medications were observed. MRI brain imaging is now widely performed among prevalent CPA users.