Although pregnancies and pregnancy-related adverse events among women taking isotretinoin (Accutane) decreased after an FDA risk evaluation and management strategy (REMS) was instituted in 2006, high-risk pregnancies still persist at a level warranting attention, researchers said.
A total of nearly 4,650 pregnancies were documented following the introduction of iPLEDGE REMS, intended to prevent fetal isotretinoin exposure and to inform clinicians about the drug’s safety and risk, reported Arash Mostaghimi, MD, MPA, MPH, of Brigham and Women’s Hospital in Boston, and colleagues.
Isotretinoin-exposed pregnancies declined over several years from 768 in 2006, stabilizing in a range of 218 to 310 after 2011, the authors wrote in JAMA Dermatology.
Pregnancies involving fetal defects were rare — just 40 during the 2006-2017 period — and eventually dropped to single digits annually after 2008, the researchers found. Some 28% of pregnancies ended in abortion, about 40% of which were spontaneous.
“Although we have made some strides, we need to continue to think about how we can improve our system to reduce risk even further,” Mostaghimi told MedPage Today.
There is a lack of evidence regarding whether iPLEDGE is effective in preventing fetal exposure to isotretinoin, noted Arielle Nagler, MD, of New York University School of Medicine in New York City, in an accompanying editorial. Although the present investigation does not provide conclusions regarding the efficacy of iPLEDGE, it is clear “fetal exposure persists at unacceptable levels,” Nagler continued.
“The REMS programs such as iPLEDGE must strike a careful balance between preserving access to medication and ensuring that the medication is used safely,” Nagler wrote. The FDA should prioritize data-driven, rate-based assessments that expand upon this study as efforts are made toward developing a successor to the iPLEDGE program, she added.
Mostaghimi’s group evaluated 6,740 pregnancies reported to the FDA from 1997 to 2017 for women taking isotretinoin. Mean age was 24.6 years. Adverse outcomes in such pregnancies were determined from the FDA Adverse Event Reporting System (FAERS), the agency’s database of drug adverse event briefs filed by manufacturers, prescribers, and consumers.
Each individual record of a pregnancy-related adverse event represented one pregnancy. Fetal defects, abortions, and pregnancies that happened while women were using contraception were counted as subgroups of the overall number of pregnancy events.
Limitations of the study include that FAERS data are submitted voluntarily and cannot be independently confirmed; adverse events related to isotretinoin-exposed pregnancy are probably underreported, the researchers indicated. Also, the FAERS data lack a denominator, i.e., the number of isotretinoin courses taken each year, making it difficult to estimate the true rate of pregnancy-related events. Nagler pointed to others, such as improved contraception efficacy in the general teen and young adult population, as well as the possibility that “reporting fatigue” reduced FAERS submissions in the study’s later years.
Overall, while it’s tempting to attribute the decline in pregnancies to the iPLEDGE REMS, the current study falls short of proving it, Nagler suggested. For their part, Mostaghimi and colleagues said more research is needed to determine how best to genuinely reduce pregnancies among isotretinoin users without unduly limiting access to the drug.
Mostaghimi disclosed relationships with Pfizer and Hims Inc.
Nagler reported no disclosures.