Isotretinoin prescribers frustrated with stalled iPledge modifications

Key takeaways:

• The AAD and the FDA recommended changes to the iPledge system, but none have yet taken place.
• The AAD’s iPledge workgroup is concerned with a lack of communication and possible defects in rollout.

It has been 9 months since the FDA released recommended changes to the iPledge Risk Evaluation and Mitigation Strategy, and providers are growing increasingly frustrated at a perceived lack of transparency and implementation plan.

The iPledge program is aimed at preventing fetal exposure to isotretinoin. It includes a centralized system used by physicians, pharmacists and patients.

For years, the American Academy of Dermatology’s iPledge workgroup has been requesting modifications to the program to increase accessibility and minimize procedural burdens.

“For 5 to 7 years my colleagues and I have been trying to work on getting some general, commonsense reforms to the iPledge program,” John S. Barbieri, MD, MBA, assistant professor at Harvard Medical School, director of the advanced acne therapeutics clinic at Brigham and Women’s Hospital and co-chair of the AAD’s iPledge workgroup, told Healio. “We know the program is designed to prevent fetal exposure to isotretinoin, but unfortunately there have been some unintended harms in terms of reducing access.”

In a 2020 article published in JAMA Dermatology, Barbieri and colleagues documented the harms of the iPledge system, which included a 30% decrease in isotretinoin prescriptions affecting both those who could and could not get pregnant, a risk for antibiotic-associated complications promoting antibiotic resistance and a delay in treatment due to administrative burdens.

They also reported an economic burden on patients, as 55% of adults and 80% of caregivers had to miss school or work for isotretinoin-related office visits.

Following a March 2023 meeting with the workgroup’s representatives, the FDA released a list of recommended modifications on Nov. 30, 2023.

Proposed modifications include:

• no longer requiring pregnancy tests be performed in a specially certified laboratory, and instead allowing home pregnancy tests during and after treatment with prescribers taking steps to minimize patient falsification;
• removing the required waiting period for patients if they do not obtain isotretinoin within the first 7 days of receiving the prescription, and instead requiring a repeated confirmation pregnancy test in a medical setting before initiating treatment;
• no longer requiring pregnancy and fetal outcome documentation; and
• only requiring documented patient counseling at enrollment vs. monthly for patients who cannot become pregnant.

The Isotretinoin Products Manufacturing Group (IPMG), a consortium of companies that make isotretinoin products, was given 6 months to respond with their own proposed modifications.

For the members of the AAD workgroup, waiting for a response has become disheartening. They are concerned not only about the recommendations and modifications themselves, but a lack of information from both the IPMG and the FDA regarding the process and the potential ramifications of a program change rollout that does not include the key stakeholders.

In 2021, the IPMG implemented a change to the iPledge online system, which caused “systemwide malfunctions,” according to an editorial published in Baylor University Medical Center Proceedings. There were hours-long wait times on support phone lines, disruptions to medication disbursement and months of work to get the new system up and running properly.

The iPledge workgroup is now worried that even if the proposed modifications to the REMS program are accepted, a similar situation could occur without input from the system’s users before rollout.

Ilona J. Frieden

“There was a complete meltdown of the entire system because of the transition,” Ilona J. Frieden, MD, professor of pediatrics and dermatology at University of California, San Francisco, and a member of the iPledge workgroup, told Healio. “We offered to beta test it ... because we are the main users. But they did not communicate with us about it. Finally, it did get resolved, but not without patients missing weeks to months of therapy.”

Having a say in how modifications go into effect could be key in a seamless transition and in ensuring patients do not miss necessary treatments, according to Barbieri.

“These are much needed reforms,” he said. “We want to make sure that they’re implemented in a way that makes sense for patients, prescribers and pharmacists. Because even if these reforms might be good, if they’re implemented poorly, it might not actually help patients at all. And that is our goal.”

Getting in contact with the IPMG, however, has proven difficult. A generic email address is the only point of contact, which the workgroup’s members say routinely goes unanswered. Multiple emails from Healio regarding this topic also did not receive a response.

“I don’t feel that we have a good partnership of trust,” Frieden said.

Andrea L. Zaenglein

“Communication is one of the biggest issues,” added Andrea L. Zaenglein, MD, professor of dermatology and pediatrics at the Pennsylvania State/Hershey Medical Center and a member of the iPledge workgroup. “Unfortunately, they are very nonresponsive and avoid collaboration with stakeholders. In this era of transparency, it is incredulous that members of the IPMG ae not made public. We are not even sure that there is a dermatologist involved in the decision making.”

The FDA’s Center for Drug Evaluation and Research, in response to a request for more information, did not confirm if the IPMG has submitted its response, but stated that the submission “will be a major modification and the review timeline is generally 6 months.”

They added that time will be needed to implement any changes once recommendations are approved and that they were not able to give any further information on its status.

As more time passes, the work group continues to grow more frustrated as implementing these changes can have a huge impact on not only their workflow, but their patients’ lives.

“Our ultimate goal is to improve outcomes for patients,” Barbieri said. “We just want to be involved in the process, or at least know what is going on in a transparent manner. We continue to be stonewalled effectively by these other parties who run the program and I worry that it will lead to poor implementation, bad outcomes and patient harm.”

References:

• Barbieri JS, et al. JAMA Dermatol. 2020;doi:10.1001/jamadermatol.2019.3270.
• Zamil DH, et al. Proc (Bayl Univ Med Cent). 2022;doi:10.1080/08998280.2022.2111643.

For more information:

John S. Barbieri, MD, MBA, can be reached at jbarbieri@bwh.harvard.edu.

Ilona J. Frieden, MD, can be reached at ilona.frieden@ucsf.edu.

Andrea L. Zaenglein, MD, can be reached at azaenglein@pennstatehealth.psu.edu.