This article includes discussion of birth defects that may be challenging for some readers.
May 25, 2023
By Clare Lipscombe, Drexel University College of Medicine
Isotretinoin, more commonly known by its brand name Accutane, is an approved therapy for the treatment of severe acne with unrivaled efficacy. However, its use can cause profound birth defects in a developing fetus. Because of this, the United States Food and Drug Administration created the iPLEDGE program in 2006 to remove the risk of fetal exposure to isotretinoin by ensuring patients are not pregnant or at risk of becoming pregnant while on a prescribed course of the medication. The iPLEDGE program is a mandatory monitoring system that requires patients, prescribers and pharmacies to enroll in a centralized database before prescribing, dispensing or receiving the medication. The program is meticulous, and disproportionately burdens women as it requires females of childbearing potential to have a pregnancy test with negative results and verification of two forms of contraception monthly. This places considerable time and financial strain on patients, and functions as a barrier to care. While a great idea in theory, in practice users have found the program to be burdensome, and prescribers worry that the imposing steps put in place by the program deter isotretinoin use in individuals who greatly need it.
Several studies have investigated the effectiveness of the iPLEDGE program in reducing pregnancy complications associated with isotretinoin use. One such study published in the Journal of the American Academy of Dermatology in 2019 found that the implementation of the iPLEDGE program did not eliminate pregnancy-related adverse events associated with isotretinoin use. Although there was an initial decrease in the number of pregnancy-related adverse events at the start of iPLEDGE in 2006, the progress has since been stagnant, with roughly 200-300 pregnancies occurring in individuals taking isotretinoin every year. Rates of pregnancy remain consistent within iPLEDGE participants, with 2.7 pregnancies exposed to isotretinoin per 1,000 treatment courses.
Not only has the program not been overwhelmingly effective, but the considerable impositions it introduces have decreased the access to isotretinoin. After the introduction of the iPLEDGE program, there was a 29% decrease in isotretinoin prescriptions despite its unrivaled efficacy and proven potential in treating acne. In a study performed in 2022 that surveyed over 500 dermatologists, it was found that more than 30% had chosen not to prescribe isotretinoin at some point because of the burden of iPLEDGE. Instead, they turned to less-efficacious alternative treatments, such as antibiotics, despite the patients being eligible for the medication. This introduces other complications such as antibiotic resistance.
The substantial financial burden placed upon patients is important as well. The routine office visits result in significant time missed from work and school for adults and children. Additionally, as iPLEDGE newly allows photo submissions of negative pregnancy tests since the move to virtual communication forms since the COVID-19 pandemic, the out-of-pocket expense required monthly by menstruating patients does not fall under insurance coverage. These statistics also fail to account for the ethical concerns with having to report contraceptive use and pregnancy status to a government agency, especially when considering that children are required to utilize iPLEDGE for isotretinoin use as well.
Given the considerable burdens and barriers that the iPLEDGE system places upon patients, new approaches for lowering fetal exposure to isotretinoin or an improved model of care delivery should be explored to ensure that patients receive the care they need.
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Sources/Resources:
- Barbieri JS, Frieden IJ, Nagler AR. Isotretinoin, Patient Safety, and Patient-Centered Care—Time to Reform iPLEDGE. JAMA Dermatol. 2020;156(1):21–22. doi:10.1001/jamadermatol.2019.3270
- Lee G, Wolf JR, Somers KE. Administrative Burden of iPLEDGE Deters Isotretinoin Prescriptions: Results From a Survey of Dermatologists. Cutis. 2022 Jul;110(1):44-47. doi: 10.12788/cutis.0558. PMID: 36179224
- Shin J., Cheetham T.C., Wong, L., et al. The impact of the iPledge program on isotretinoin fetal exposure in an integrated health care system. J Am Acad Dermatol. 2011; 65: 1117-1125
- 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. 2019;155(10):1175–1179. doi:10.1001/jamadermatol.2019.1388