Isotretinoin Retrial in Patients with Acne Relapse
In this video, John Barbieri, MD, MBA, FAAD, dermatologist and epidemiologist at Brigham and Women’s Hospital and Harvard Medical School, discusses his recent study examining factors that influence acne recurrence following isotretinoin treatment. Dr. Barbieri highlights the importance of flexible dosing strategies to balance efficacy and side effects and suggests tailoring cumulative doses to optimize outcomes and prioritized shared decision-making with patients.
Additional Resource:
- Lai J, Barbieri JS. Acne Relapse and Isotretinoin Retrial in Patients With Acne. JAMA Dermatol. 2025;161(4):367-374. doi:10.1001/jamadermatol.2024.5416
TRANSCRIPTION:
John Barbieri, MD, MBA, FAAD: Hey everyone, I'm Dr. John Barbieri. I'm a dermatologist and epidemiologist at the Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts.
Consultant360: What motivated you to conduct this study?
Dr Barbieri: We were interested in trying to understand what are factors that lead to patients needing to get additional treatment after isotretinoin because when we're using isotretinoin, we're often trying to achieve a long-term acne clearance and we wanted to understand other factors in terms of dosing or patient selection that are predictive of this so that we can be thoughtful about our approach to using isotretinoin to try to maximize patient outcomes.
C360: How did you approach answering those questions?
Dr Barbieri: To get at this question, we used a claims database called MarketScan, so this is data about healthcare encounters, medication prescriptions, and demographic information. And we created a cohort of individuals who are receiving their fourth treatment course of isotretinoin. We wanted them to have at least several months of treatment to really ensure that they didn't just stop it after a month because the logistical barriers or side effects, so patients who really got at least some of a course of treatment. And then we looked in the subsequent time period for, did those individuals who completed that course of isotretinoin, did they end up getting another topical medication for acne, another systemic medication for acne, or another course of isotretinoin? And we also tried to look at different factors like dosing, age, and sex while we were doing that.
C360: Did you find any variation across different demographics?
Dr Barbieri: When it comes to our findings, one of the first things we found is that about 10% of people end up going on to have a second course of isotretinoin, and about 20 % of people will end up having some systemic treatment for acne after finishing that first course of isotretinoin. And I think this fits with some other studies in the literature that suggest about a fifth of people will have some meaningful recurrence of acne after completing a course of isotretinoin.
We also looked at different factors like age, sex, and dosing. We found that in general, people who are older when they started this first course of isotretinoin were less likely to have acne to come back. That's, I think, been shown some other studies. We also found that women were more likely to have acne come back than men.
Finally, we looked at dosing, and we found that cumulative dose, so having higher total amounts of milligrams of isotretinoin per estimated body sizes individuals, was generally associated with lower rates of acne recurrence. However, at cumulative doses above 220 milligrams per kilogram, we started to not see that effect anymore. In addition, we really didn't see any effects of daily dose. So long as people were reaching a sufficient cumulative dose, it didn't seem to matter that much whether they were getting a low dose, kind of a more standard, or a high daily dose of isotretinoin in terms of milligram per kilogram per day.
C360: Did anything about the study results surprise you?
Dr Barbieri: One of the things that I was surprised by was that we kind of saw this plateauing effect of cumulative dose. We had seen in some earlier observational studies that it seems like higher cumulative doses were associated with better rates of long-term clearance, and there had been this general push towards using higher and higher cumulative doses over time, I think. It was interesting in our data that we do seem to see, again, that effect that more cumulative dose is helpful in terms of preventing recurrence, but also there seems to be some point where it doesn't really help that much more. I do experience these patients in my practice who will get like 90 or 95% better on isotretinoin and kind of just get stuck, even when using better adsorbed formulations like micronized isotretinoin, often sometimes there's some other contributing factor like polycystic ovarian syndrome and typically in my experience, switching actually and going to hormonal therapy or some other treatment option can work really well in these people, even if that didn't work before who get a lot better but don't get fully clear.
C360: What are the most important takeaways for clinicians treating this cohort?
Dr. Barbieri: For me, one of the first takeaways is, I think the study really gives us some new insights about the potential to be more flexible in our dosing approaches. I think we often kind of feel like higher is better when it comes to isotretinoin, but I do think we want to be thoughtful about balancing the benefits of higher doses with the potential side effects and risks, so in our data, we really don't see much advantage using higher daily doses of treatment. And we know that most of the side effects of isotretinoin are pretty dose dependent, so higher dose has more dryness, more joint pains, more of most of those kinds of side effects we worry about. So for those who are willing to have potentially a longer course to reach that same cumulative dose, but would like to have less side effects, using a lower daily dose, our data supports, this can be done and lead to good long-term outcomes as well. Certainly there might be other reasons we to do a higher daily dose to try and get done faster because of concerns about eye pledge logistics or pregnancy prevention, those types of things. But I think this, these data give us some flexibility to use lower dose regimens as long as we're getting to a sufficient cumulative dose and still achieve really good long-term outcomes.
I think they also give us some insights into what populations might be at higher risk of having their acne come back. So younger individuals, we note, are more likely to have acne recurrence after isotretinoin, and since we know cumulative dose is protective for recurrence, we might want to go to a higher cumulative dose in a younger individual with acne than an older individual all else equal to try to minimize the likelihood that acne comes back after they stop.
And then finally, when it comes to cumulative dose, I do think we have to be thoughtful about long-term risk of isotretinoin. People I do think can get sometimes long-term skin or eye dryness and so especially in those who are having a lot of dry skin symptoms, I think we have to be careful about trying to go for the highest possible cumulative dose and accept some potential higher risk of recurrence to try to minimize long-term risk of side effects and just to be thoughtful about always balancing those and having shared decision-making with the patients.