Original Research

Administrative Burden of iPLEDGE Deters Isotretinoin Prescriptions: Results From a Survey of Dermatologists

Cutis. 2022 July;110(1):44-47 | doi:10.12788/cutis.0558

The requirements of the iPLEDGE program place burdens on both patients with severe recalcitrant nodular acne and prescribers of isotretinoin. We sought to investigate the changes in dermatologists’ acne treatment patterns due to the administrative burden of iPLEDGE by assessing whether dermatologists chose not to prescribe isotretinoin to appropriate patients because of the labor of iPLEDGE requirements. Additionally, we investigated the medications that were substituted for isotretinoin. An anonymous online survey was created and posted on a dermatology group on social media. The survey respondents (N=510) consisted of board-certified dermatologists across the United States and comprised a wide variety of ages and practice types. This survey ultimately highlighted the burden of iPLEDGE for American clinicians and the need for a more streamlined risk-management program. This program is deterring some US clinicians, especially those younger than 46 years, from prescribing isotretinoin and limiting patient access to an effective medication.

PDF Download

Practice Points

Of clinicians who regularly prescribe isotretinoin, approximately 30% have at times chosen not to prescribe isotretinoin to patients with severe acne because of the burden of the iPLEDGE program.
The US Food and Drug Administration should consider further streamlining the iPLEDGE program, as it is causing physician burden and therefore suboptimal treatment plans for patients.

References

Prevost N, English JC. Isotretinoin: update on controversial issues. J Pediatr Adolesc Gynecol. 2013;26:290-293.
Tkachenko E, Singer S, Sharma P, et al. US Food and Drug Administration reports of pregnancy and pregnancy-related adverse events associated with isotretinoin. JAMA Dermatol. 2019;155:1175-1179.
Shin J, Cheetham TC, 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.
iPLEDGE Program. About iPLEDGE. Accessed June 13, 2022. https://ipledgeprogram.com/#Main/AboutiPledge
Marson JW, Baldwin HE. An overview of acne therapy, part 2: hormonal therapy and isotretinoin. Dermatol Clin. 2019;37:195-203.
Margolis DJ, Fanelli M, Hoffstad O, et al. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease. Am J Gastroenterol. 2010;105:2610-2616.
Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-973.e33.
iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). Updated January 14, 2022. Accessed June 13, 2022. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/ipledge-risk-evaluation-and-mitigation-strategy-rems
Huang YC, Cheng YC. Isotretinoin treatment for acne and risk of depression: a systematic review and meta-analysis. J Am Acad Dermatol. 2017;76:1068-1076.e9.

Isotretinoin is the most effective treatment of recalcitrant acne, but because of its teratogenicity and potential association with psychiatric adverse effects, it has been heavily regulated by the US Food and Drug Administration (FDA) through the iPLEDGE program since 2006.^1,2 To manage the risk of teratogenicity associated with isotretinoin, various pregnancy prevention programs have been developed, but none of these programs have demonstrated a zero fetal exposure rate. The FDA reported 122 isotretinoin-exposed pregnancies during the first year iPLEDGE was implemented, which was a slight increase from the 120 pregnancies reported the year after the implementation of the System to Manage Accutane-Related Teratogenicity program, iPLEDGE’s predecessor.³ The iPLEDGE program requires registration of all wholesalers distributing isotretinoin, all health care providers prescribing isotretinoin, all pharmacies dispensing isotretinoin, and all female and male patients prescribed isotretinoin to create a verifiable link that only enables patients who have met all criteria to pick up their prescriptions. For patients of reproductive potential, there are additional qualification criteria and monthly requirements; before receiving their prescription every month, patients of reproductive potential must undergo a urine or serum pregnancy test with negative results, and patients must be counseled by prescribers regarding the risks of the drug and verify they are using 2 methods of contraception (or practicing abstinence) each month before completing online questions that test their understanding of the drug’s side effects and their chosen methods of contraception.⁴ These requirements place burdens on both patients and prescribers. Studies have shown that in the 2 years after the implementation of iPLEDGE, there was a 29% decrease in isotretinoin prescriptions.^1-3

We conducted a survey study to see if clinicians chose not to prescribe isotretinoin to appropriate candidates specifically because of the administrative burden of iPLEDGE. Secondarily, we investigated the medications these clinicians would prescribe instead of isotretinoin.

Methods

In March 2020, we administered an anonymous online survey consisting of 12 multiple-choice questions to verified board-certified dermatologists in the United States using a social media group. The University of Rochester’s (Rochester, New York) institutional review board determined that our protocol met criteria for exemption (IRB STUDY00004693).

Statistical Analysis—Primary analyses used Pearson χ² tests to identify significant differences among respondent groups, practice settings, age of respondents, and time spent registering patients for iPLEDGE.

Results

Survey results from 510 respondents are summarized in the Table.

Burden of iPLEDGE—Of the respondents, 336 (65.9%) were frequent prescribers of isotretinoin, 166 (32.5%) were infrequent prescribers, and 8 (1.6%) were never prescribers. Significantly more isotretinoin prescribers estimated that their offices spend 16 to 30 minutes registering a new isotretinoin patient with the iPLEDGE program (289 [57.6%]) compared with 0 to 15 minutes (140 [27.9%]), 31 to 45 minutes (57 [11.3%]), and morethan 45 minutes (16 [3.2%])(χ²₃=22.09, P<.0001). Furthermore, 150 dermatologists reported sometimes not prescribing, and 2 reported never prescribing isotretinoin because of the burden of iPLEDGE.

Systemic Agents Prescribed Instead of Isotretinoin—Of the respondents, 73.0% (n=111) prescribed spironolactone to female patients and 88.8% (n=135) prescribed oral antibiotics to male patients instead of isotretinoin. Spironolactone typically is not prescribed to male patients with acne because of its feminizing side effects, such as gynecomastia.⁵ According to the American Academy of Dermatology guidelines on acne, systemic antibiotic usage should be limited to the shortest possible duration (ie, less than 3–4 months) because of potential bacterial resistance and reported associations with inflammatory bowel disease, Clostridium difficile infection, and candidiasis.^6,7

Administrative Burden of iPLEDGE Deters Isotretinoin Prescriptions: Results From a Survey of Dermatologists

References

Methods

Results

Pages

Recommended Reading