(106) Impact of Regulatory Interventions on Ulipristal Acetate (Esmya) Use in Spain: An Interrupted Time-Series Analysis

Publication Number: 437

Background: Since late 2017 the use of ulipristal acetate 5mg (Esmya) has been under review in the European Union, due to an emerging hepatic risk associated to its use. In February 2018 and in July 2018 the Spanish Agency of Medicines and Medical Devices issued two expedited communications for healthcare professionals that highlighted the importance of adhering to the changes in the authorization conditions regarding restriction of use, new contraindication and the need to monitor hepatic function during Esmya treatment. The marketing authorization holder delivered shortly after two Dear Health Care Professional letters, in order to inform about the new safety information.

Objectives: To assess the effectiveness of the risk minimization measures (RMMs).

Methods: Two quasi-experimental interrupted time-series analyses to examine the use of ulipristal acetate before and after the communication of the RMMs were performed: a) an ecological study using aggregated data from a drug consumption database and b) a study using primary healthcare data gathered from electronic clinical records. Both studies covered the period between 1st January 2014 to 31st December 2019.
The number of Defined Daily Dose dispensed per 100,000 inhabitants and day (DDD/100,000 inhabitants/day = DID) was calculated per quarter. The cumulative incidence was calculated per 100,000 patients by dividing the number of new Esmya users by the number of patients from the study population in the corresponding quarters. Since the release of the different interventions were close, an intervention period that covered the timing in which the corresponding RMMs under study were disseminated was considered. Therefore all interventions were assessed in a single stage.

Results: Regulatory actions taken were associated with an immediate and significant falling level of DID and incidence. The DID was 70% less than expected 12 months after the interventions. This value was 59% for the incidence. Despite the immediate high decrease of Esmya use after the intervention, a change in the slope was not observed and the use started rising again in the last segment of the study period from 1.0 DID and 0.4 new users per 100,000 patients in the third quarter 2018, to 7.0 DID and 5.0 new users per 100,000 patients in the last quarter 2019.

Conclusions: The RMMs had an immediate strong impact on Esmya use. Nevertheless, the downward trend in the long-term might have been affected by the lack of comparable effective drugs. Further studies will be needed in order to confirm the increase trend observed in the last segment of the study period in the long term.