Make lab monitoring of patents taking isotretinoin less routine, more based on symptoms

Ask Claude, the artificial intelligence agent, whether isotretinoin causes liver damage, and the answer it gives is that for most people the acne medicine doesn’t, but that it can cause a measurable increase in liver enzyme,“ which is why it's not an over-the-counter or unsupervised medication — it requires blood work before and during treatment, and dermatologists adjust or stop the drug if levels rise too much.”

But in a viewpoint published in JAMA Dermatology today, three University of Vermont dermatologists call for the end of routine testing of liver enzymes for people taking isotretinoin. For people without risk factors, the testing should be based on symptoms, say the viewpoint authors. They argue for taking a similar symptom-based approach to testing for increased levels triglycerides, which

Symptom-based monitoring would reduce patients’ worries about what may be temporary increases in liver enzyme and triglyceride levels and lower costs for patients and the healthcare system overall, write Joseph C. Pierson, M.D., chair of the University of Vermont Health dermatology department and two residents, Taylor M. Pong, M.D., and Mark L. Derbyshire, M.D.

Costs are becoming increasingly problematic as health insurance increasingly tilts toward coverage with high deductibles, Pierson, Pong and Derbyshire write. “We have a responsibility to be better stewards of healthcare resources and, when evidence supports it, seize opportunities to conserve, especially when our efforts reduce financial strain on patients and the system overall.”

Isotretinoin has a fraught history. Developed by Hoffman-La Roche and sold under the brand name Accutane, concerns about possible side effects emerged soon after it was approved by the FDA in 1982. When it was linked to an increased risk of birth defects, the FDA required that Accutane have a boxed warning. A special risk evaluation and mitigation strategies (REMS) program was created to steer people who are pregnant or might become so from taking isotretinoin. Some adverse event data has suggested a link to suicide, and there has been litigation about whether isotretinoin might cause inflammatory bowel disease.

But studies have also shown that isotretinoin is effective and that the side effects, which include mucocutaneous dryness and joint aches, can be managed or avoided through patient selection. In 2022, an international group of experts using a Delphi consensus process backed away from recommendations for monthly testing for liver enzymes, specifically alanine aminotransferase, and triglycerides to what Pierson and his colleagues referred to as a “more streamlined approach” of a baseline test and then another once the peak dose is reached. In their JAMA Dermatology viewpoint, they argue for raking back routine testing even further to a protocol that would reserve it for patients experiencing symptoms.

To back up their opinion, Pierson, Pong and Derbyshire cite a review published in the British Journal of Dermatology in 2022 that included 125 articles. The authors found that adverse events detected by blood tests occurred less than once in every 10, 000 tests. Their takeaway was similar to the case that Pierson, Pong and Derbyshire are making. “We suggest that in healthy young people laboratory monitoring for oral isotretinoin is unnecessary and risks detecting nonserious biochemical abnormalities. However, we recognize that new information about adverse events may change that recommendation,” they wrote in the abstract.

The National Institute of Health’s LiverTox database assigns isotretinoin a drug-induced likelihood score of D, which translates into it being a possible cause, according to Pierson, Pong and Derbyshire. That rating means there is at least one case report but no more than three, and “no characteristic signature has been identified,” they wrote. Other dermatologic drugs with a D score include spironolactone, ivermectin and acyclovir. They note that terbinafine, an antifungal sold under the brand name Lamisil, has an A score and evidence of drug-induced injury once every 50,000 to 120,000 prescriptions. Yet it has a symptom-based approach to liver testing.

John S. Barbieri, M.D., MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, was the lead author of one of the studies cited by Pierson, Pong and Derbyshire. In an email interview with Managed Healthcare Executive, Barbieri said many dermatologists who order blood tests for their patients taking isotretinoin on a regular, sometimes monthly, basis. He said his standard approach is the one that emerged from the Delphi consensus project: tests for alanine aminotransferase and triglycerides at baseline and at the peak dose. Barbieri said that that approach to blood tests for isotretinion is most aligned with the current American Academy of Dermatology Acne Guidelines.

“That being said,” Barbieri added, “I do not believe that laboratory monitoring is required and that it can be deferred after a thorough discussion of risks and benefits as part of shared decision-making.”

Barbieri said it was important to monitor patients taking isotretinoin for “addressable” side effects such as mucocutaneous dryness, joint pains and muscle aches. Those side effects can often be managed by reducing the dose or advising patients to take supplements such as omega-3 fats and L-carnitine, respectively. It is rare, he said, but mood changes and vision changes can occur and might require a change in treatment. Barbieri added that pregnancy prevention and counseling is paramount among persons of childbearing potential.

“I think the key point is that monitoring strategies should be individualized based on patient risk factors rather than applying intensive laboratory surveillance to all patients receiving isotretinoin,” Barbieri summed up..