(B-051) Evaluation of the effectiveness of pregnancy prevention programme (PPP) for oral retinoids (acitretin, alitretinoin, and isotretinoin): a European before-after drug utilisation study (DUS) using secondary data

Background: Oral retinoids are used to treat severe acne and other skin conditions. Retinoid therapy is associated with teratogenicity. Strict prescription guidelines and a PPP have been put in place, but exposure during pregnancy still occurs. The European Medicines Agency (EMA)requested MAHs to strengthen the PPP and mandated a DUS to assess the effectiveness of the updated risk minimisation measures.

Objectives: To evaluate changes in prescribing behaviour following the update of the PPP in females of childbearing potential receiving oral retinoids prescriptions.

Methods: The study employed a multisource, observational cohort design using secondary data in France, Germany, Spain, and Sweden with a pre-post comparison. Changes in prescribing were assessed across for the pre-referral period (July 2014 - June 2016), and the post-implementation period (from the implementation month of updated RMMs in each country to December 2020). The analysis focused on 3 key aspects of contraceptive prescription use: 30-day use prior to initiating oral retinoid treatment, continuous concomitant use during treatment, and 30-day use after treatment cessation.

Results: The study sample in the pre-referral period/post-implementation period comprised 87,818/92,582 patients on oral retinoid treatment in France, 1,953/1,598 patients in Germany, 3,004/4,100 patients in Spain, and 9,182/16,709 patients in Sweden.
In the pre-referral period, a 30-day contraceptive prescription prior to oral retinoid treatment start / continuous concomitant contraceptive prescriptions / a 30-day contraceptive prescription after treatment stop was observed in 38.9%/35.2%/43.8% (France), 8.6%/7.0%/8.8% (Germany), 14.5%13.5%/16.1% (Spain) and 33.1%/32.3%/38.9% (Sweden) of treatment episodes.
The corresponding numbers in the post-implementation period were 42.3%/38.1%/46.7% (France), 11.0%/9.4%/11.0% (Germany), 14.1%/13.0%/17.0% (Spain) and 39.2%/40.3%/44.6% (Sweden), respectively.

Conclusions: Positive trends were observed in the 3 countries (Germany, France and Sweden) with respect to PPP adherence from the pre- to the post-implementation periods of the updated PPP with respect to contraceptive use. It needs to be noted that these changes were generally of small magnitude and likely impacted by safety measures and behaviours associated with the COVID-19 pandemic in 2020.