Compliance with Pregnancy Prevention Recommendations for Isotretinoin Following the Amendment of the European Union Pregnancy Prevention Program: A Repeat Study in Estonia.
Journal
Drugs - real world outcomes
ISSN: 2199-1154
Titre abrégé: Drugs Real World Outcomes
Pays: Switzerland
ID NLM: 101658456
Informations de publication
Date de publication:
18 Jul 2023
18 Jul 2023
Historique:
accepted:
27
06
2023
medline:
18
7
2023
pubmed:
18
7
2023
entrez:
18
7
2023
Statut:
aheadofprint
Résumé
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. 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. 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. 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). 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 37462893
doi: 10.1007/s40801-023-00381-3
pii: 10.1007/s40801-023-00381-3
doi:
Types de publication
Journal Article
Langues
eng
Informations de copyright
© 2023. The Author(s).
Références
Graber E. Acne vulgaris: overview of management. UpToDate, Post TW (Ed), UpToDate, Waltham, MA.
Rosa FW. Teratogenicity of Isotretinoin. Lancet. 1983;322:513.
doi: 10.1016/S0140-6736(83)90538-X
Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, et al. Retinoic acid embryopathy. N Engl J Med. 1985;313:837–41.
doi: 10.1056/NEJM198510033131401
pubmed: 3162101
Crijns HJMJ, Straus SM, Gispen-de Wied C, de Jong-van den Berg LTW. Compliance with pregnancy prevention programmes of isotretinoin in Europe: a systematic review. Br J Dermatol [Internet]. 2011;164:238–44. https://doi.org/10.1111/j.1365-2133.2010.09976.x .
doi: 10.1111/j.1365-2133.2010.09976.x
pubmed: 20716214
Retinoid-containing medicinal products | European Medicines Agency [Internet]. https://www.ema.europa.eu/en/medicines/human/referrals/retinoid-containing-medicinal-products . Accessed 28 Nov 2022.
Uusküla A, Pisarev H, Kurvits K, Laius O, Laanpere M, Uusküla M. Compliance with pregnancy prevention recommendations for isotretinoin in Estonia in 2012–2016. Drugs Real World Outcomes [Internet]. 2018;5:129–36. https://doi.org/10.1007/s40801-018-0135-z .
doi: 10.1007/s40801-018-0135-z
pubmed: 29790022
pmcid: 5984611
Henry D, Dormuth C, Winquist B, Carney G, Bugden S, Teare G, et al. Occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy. Can Med Assoc J [Internet]. 2016;188:723–30. https://doi.org/10.1503/cmaj.151243 .
doi: 10.1503/cmaj.151243
Pinheiro SP, Kang EM, Kim CY, Governale LA, Zhou EH, Hammad TA. Concomitant use of isotretinoin and contraceptives before and after iPledge in the United States. Pharmacoepidemiol Drug Saf [Internet]. 2013;22:1251–7. https://doi.org/10.1002/pds.3481 .
doi: 10.1002/pds.3481
pubmed: 23913625
Teichert M, Visser LE, Dufour M, Rodenburg E, Straus SMJM, De Smet PAGM, et al. Isotretinoin use and compliance with the Dutch pregnancy prevention programme: a retrospective cohort study in females of reproductive age using pharmacy dispensing data. Drug Saf [Internet]. 2010;33:315–26. https://doi.org/10.2165/11319190-000000000-00000 .
doi: 10.2165/11319190-000000000-00000
pubmed: 20297863
Hughes JE, Buckley N, Looney Y, Kirwan G, Mullooly M, Bennett KE. Evaluating awareness, knowledge and practice of healthcare professionals following implementation of a revised pregnancy prevention programme for isotretinoin in Ireland: a multi-stakeholder cross-sectional study. Pharmacoepidemiol Drug Saf. 2023;32:137–47.
doi: 10.1002/pds.5538
pubmed: 36073295
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61:344–9.
doi: 10.1016/j.jclinepi.2007.11.008
Estonian Health Insurance Fund (2022) [Internet]. https://statistika.haigekassa.ee/PXWeb/pxweb/et/kindlustatu/kindlustatu__Kindlustus/KN05.px/table/tableViewLayout2/?rxid=edfa6b1b-be27-4b15-86ef-1f0228a0af43 . Accessed 15 Mar 2022.
Rahvaarv | Statistikaamet [Internet]. https://www.stat.ee/et/avasta-statistikat/valdkonnad/rahvastik/rahvaarv . Accessed 15 Mar 2022.
WHOCC—Home [Internet]. https://www.whocc.no/ . Accessed 16 Apr 2022.
Estonian State Agency of Medicines. Register of Medicinal Products. [Internet]. https://ravimiregister.ee/en/publichomepage.aspx . Accessed 16 Apr 2022.
Health Products Regulatory Authority. Depo-Provera 150 mg/ml Suspension for injection. Summary of product characteristics. 2021. http://www.hpra.ie/img/uploaded/swedocuments/Licence_PA0822-124-001_21062021164149.pdf . Accessed 16 Apr 2022.
R Core Team (2021). R: a Language and Environment for Statistical Computing. R Foundation for Statistical Computing [Internet]. Vienna, Austria; https://www.r-project.org/ .
Kurvits K, Laius O, Uusküla M, Laanpere M. Trends in the use of hormonal contraception in Estonia 2005–2019 and the risk of arterial and venous thromboembolism: a population-based study. Eur J Contracept Reprod Heal Care [Internet]. 2021;26:413–20. https://doi.org/10.1080/13625187.2021.1931839 .
doi: 10.1080/13625187.2021.1931839
21st ISoP Annual Meeting "A New Era of Pharmacovigilance: Challenges and Opportunities” 20–23 September 2022 Verona, Italy. Drug Saf [Internet]. 2022;45:1111–327. https://doi.org/10.1007/s40264-022-01219-7
The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. Impact of EU label changes and revised pregnancy prevention programme for oral retinoid containing medicinal products: utilization and prescribing trends [Internet]. https://www.encepp.eu/encepp/viewResource.htm?id=45887 . Accessed 4 Dec 2022.
Lõhmus L, Lemsalu L, Rüütel K, Vals K. Eesti täiskasvanud elanikkonna seksuaalkäitumine. Uuringuraport 2017. [Internet]. Tallinn: Tervise Arengu Instituut; 2018. https://tai.ee/sites/default/files/2021-03/153501440828_Eesti_täiskasvanud_elanikkonna_seksuaalkäitumine_2017.pdf
Biset N, Lelubre M, Amighi K, Bugnon O, Schneider MP, De Vriese C. Assessment of medication adherence and responsible use of isotretinoin and contraception through Belgian community pharmacies by using pharmacy refill data. Patient Prefer Adherence. 2018. https://doi.org/10.2147/PPA.S149355 .
doi: 10.2147/PPA.S149355
pubmed: 29403267
pmcid: 5783016
Ottep K, Laanpere M, Ringmets I. Rasestumisvastaste meetodite kasutamine 16–44 aastaste naiste hulgas Eestis: levimus, sotsiaal-majanduslikud ja tervishoiuteenustega seotud võimalikud barjäärid. Eesti Arst. 2019;98:135–43.
The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. Study of impact of EU label changes and revised pregnancy prevention programme (PPP) for oral retinoid-containing medicines: risk awareness and adherence [Internet]. https://www.encepp.eu/encepp/viewResource.htm?id=40650 . Accessed 4 Dec 2022.
Lelubre M, Hamdani J, Senterre C, Amighi K, Peres M, Schneider MP, et al. Evaluation of compliance with isotretinoin PPP recommendations and exploration of reasons for non-compliance: survey among French-speaking health care professionals and patients in Belgium. Pharmacoepidemiol Drug Saf [Internet]. 2018;27:668–73. https://doi.org/10.1002/pds.4441 .
doi: 10.1002/pds.4441
pubmed: 29726056
Brinker A, Kornegay C, Nourjah P. Trends in adherence to a revised risk management program designed to decrease or eliminate isotretinoin-exposed pregnancies: evaluation of the accutane SMART program. Arch Dermatol [Internet]. 2005;141:563–9. https://doi.org/10.1001/archderm.141.5.563 .
doi: 10.1001/archderm.141.5.563
pubmed: 15897377
Crijns I, Straus S, Luteijn M, Gispen-de Wied C, Raine J, de Jong-van den Berg L. Implementation of the harmonized EU Isotretinoin Pregnancy Prevention Programme: a questionnaire survey among European Regulatory Agencies. Drug Saf [Internet]. 2012;35:27–32. https://doi.org/10.2165/11595570-000000000-00000 .
doi: 10.2165/11595570-000000000-00000
pubmed: 22050373
Tkachenko E, Singer S, Sharma P, Barbieri J, Mostaghimi A. US food and drug administration reports of pregnancy and pregnancy-related adverse events associated with isotretinoin. JAMA Dermatol [Internet]. 2019;155:1175–9. https://doi.org/10.1001/jamadermatol.2019.1388 .
doi: 10.1001/jamadermatol.2019.1388
pubmed: 31314041
Lee G, Wolf JR, Somers KE. Administrative Burden of iPLEDGE Deters Isotretinoin Prescriptions: Results From a Survey of Dermatologists. Cutis [Internet]. Frontline Medical Communications Inc; 2022;110:44–7. https://www.mdedge.com/dermatology/article/256053/acne/administrative-burden-ipledge-deters-isotretinoin-prescriptions .