Can Topical Retinoids Decrease Atrophic Scars?

Topical retinoids such as trifarotene and fixed combinations of adapalene and benzoyl peroxide may be able to decrease atrophic scars in patients with active acne, according to Linda Stein Gold, MD. During the 2023 Acne and Rosacea Meeting’s (ARM) Yourself With Knowledge webinar, organized by Masterclasses in Dermatology, Stein Gold reviewed different topical retinoid formulations and their ability to decrease atrophic scars at 3 and 6 months.

Stein Gold, a board-certified dermatologist and the director of clinical research in the department of dermatology at Henry Ford Hospital presented previous studies that looked at the fixed combination of adapalene 0.1% and 2.5% benzoyl peroxide in a split-based study to prevent atrophic scars. Compared to vehicle, no new scars developed with adapalene and benzoyl peroxide. In an additional split-based study, investigators studied a stronger concentration of adapalene, adapalene .3%, in a fixed combination with 2.5% benzoyl peroxide and patients with a mean of approximately 12 scars on each side of the face. The study found that the higher fixed combination not only prevented atrophic scars, but also decreased the number of scars from 12 down to 9.5.

Trifarotene is a RAR-γ receptor that was also evaluated in a split-based study that found over the course of 6 months of treatment, scars were reduced by 6. “We can now decrease scars potentially with a topical retinoid, and these atrophic scars are kind of in flux, so we have a narrow window of opportunity to really get control of these [scars] when a patient still has active acne,” said Stein Gold.

Transcript

Linda Stein Gold, MD: What's new in topical retinoids? We have some new developments actually with each one of them. Tretinoin, which was kind of the grandfather of topical retinoids, has been developed in a lotion formulation of .05%, and it appears to be better tolerated than the other tretinoin formulations. Tazarotene lotion is now available in a 0.45% with an enhanced vehicle. This gives us the same efficacy as the .1% cream, but it's better tolerated. And then finally, we have trifarotene which was specifically formulated to the RAR-γ receptor. And in clinical trials we had the unique pleasure actually of studying this not only on the face but also on the trunk, and it worked well and was equally well tolerated both on the face as well as the body. We talked about the fact that we can have sequelae of acne, including atrophic scarring. We know that we can use devices to try to get this going under control. But is there a way to do this with topical medication? What about retinoids?

In the past, we had a study that looked at the fixed combination of adapalene 0.1% and 2.5% benzoyl peroxide, and they did a split-based study looking to see if they could prevent the development of atrophic scars. And what they found was as compared with vehicle, there were no new scars that developed over the course of 24 weeks on the active side. But there were increased scars that developed on the vehicle side. So here we saw that over 6 months we could prevent the development of atrophic scars. But taking it a step further, we then had a study using the stronger concentration of adapalene, the .3% in fixed combination with a 2.5% benzoyl peroxide. Again, a split-based study looking at patients over the course of 24 weeks, and they had a minimum or a mean of about 12 scars on each side of the face. And they treated half and half. And what we found was this time, with the higher concentration of adapalene, not only could we prevent scars from developing, but we actually saw a decrease in the number of scars. They went from 12 down to about 9.5, and on the vehicle side, it increased from 12 to about 13.3. So, this was the first time we actually found that we could actually decrease atrophic scars by using a potent topical retinoid. Here's an example of a patient and these patients had moderate acne at baseline. Notice that the acne at the end of 12 weeks and this is when we stop our clinical trials. We see a nice improvement, but the improvement is much more dramatic as we go from month 3 to month 6. We also see an improvement in the scars.

So, can we do even better? We have this new topical retinoid trifarotene which was targeted for the RAR-γ receptor, and we have a scar study here that again does a split-based study, half the study active drug half the study vehicle. They gave them a strict skin care regimen of gentle cleanser moisturizer and sunscreen. And we look to see what happens when you treat over the course of 6 months. And here we found an even more potent and more substantial reduction in the atrophic scars. We reduced the scars over 6 months by about 6. There was a little bit of a decrease on the vehicle side by 2.7. But we're really seeing that we can now decrease scars potentially with a topical retinoid and that these atrophic scars are kind of in flux and we have a narrow window of opportunity to really get control of these when a patient still has active acne. Here's a patient in the trifarotene study over the course of about 3 months and then 6 months, and then another patient with a really nice improvement, not only the acne but also the appearance of scars.

[Transcript lightly edited for clarity]

Reference

Stein Gold L. New developments in topical retinoids and scar minimization. Presented at: 2023 ARM Yourself With Knowledge: Acne and Rosacea Meeting; October 3, 2023.