Compliance with Pregnancy Prevention Recommendations for Isotretinoin Following the Amendment of the European Union Pregnancy Prevention Program: A Repeat Study in Estonia

Maaja Ivask; Katrin Kurvits; Maia Uusküla; Anne Juppo; Ott Laius; Mia Siven

doi:10.1007/s40801-023-00381-3

Compliance with Pregnancy Prevention Recommendations for Isotretinoin Following the Amendment of the European Union Pregnancy Prevention Program: A Repeat Study in Estonia

Drugs Real World Outcomes. 2024 Mar;11(1):91-98. doi: 10.1007/s40801-023-00381-3. Epub 2023 Jul 18.

Authors

Maaja Ivask^{1

2}, Katrin Kurvits³, Maia Uusküla³, Anne Juppo⁴, Ott Laius³, Mia Siven^{4

5}

Affiliations

¹ Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. maaja.ivask@helsinki.fi.
² Roche International Pharmacovigilance, Roche Eesti OÜ, Tallinn, Estonia. maaja.ivask@helsinki.fi.
³ State Agency of Medicines, Tartu, Estonia.
⁴ Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
⁵ Helsinki Institute of Sustainability Science, HELSUS, Helsinki, Finland.

Abstract

Background: Isotretinoin, indicated for severe acne, is a potent teratogen and therefore contraindicated in pregnancy. Thus, the pregnancy prevention program (PPP) for isotretinoin has been introduced.

Objectives: The aim of this study was to assess the concomitant use of isotretinoin and effective contraception and the rate of potential isotretinoin-exposed pregnancies in females of childbearing age in 2017-2020 in Estonia. In addition, we aimed to evaluate whether compliance with the PPP has improved compared with the previous study conducted in Estonia covering the period of 2012-2016.

Methods: This retrospective, nationwide study using prescription and healthcare claims data included 2575 females aged 15-45 years who started using isotretinoin between 2017 and 2020.

Results: For 64.7% of females of childbearing age, no concurrent use of an effective contraceptive was detected while using isotretinoin. A moderately higher contraceptive coverage (35.3%) was observed compared with the previous study (29.7%) (p < 0.001). Complete contraception coverage was highest in females aged 30-39 years with an adjusted OR of 12.8 (p < 0.001) compared with the age group 15-19 years and 2.47 (p < 0.001) compared with the age group 20-29 years. 17 pregnancies coincided with the isotretinoin treatment-related period. The risk for potential isotretinoin-exposed pregnancy was 6.6 (95% CI 3.9-10.5) per 1000 treated females of childbearing age over the 4-year observation period. The risk for potential isotretinoin-exposed pregnancies per 1000 treated females was 1.0 in females aged 15-19 years, 11.6 in females aged 20-29 years, 8.8 in females aged 30-39 years, and 7.4 in females aged 40-45 years (p = 0.009).

Conclusion: A slight improvement in complete contraceptive coverage during isotretinoin use has not resulted in a decrease in the risk of isotretinoin-exposed pregnancies. The contraceptive usage and risk for pregnancy vary greatly across age groups, suggesting the need for a more targeted approach to improve the effectiveness of the PPP.