Adapalene 0.3% may help improve the appearance of atrophic acne scars

A group of researchers sponsored by Galderma, a subsidiary of Nestle, have published the results of a series of experiments looking at the effect that Adapalene had on the prevention and treatment of atrophic scarring as well as acne.

Source: Art of Dermatology

Atrophic scarring is caused by a loss of tissue, so they can appear as sunken areas in the skin or even as holes, commonly referred to as ‘ice pick’ scars.

There were three experiments in total, a pilot study with 20 participants that compared Adapalene 0.3% gel compared to a control vehicle, another pilot study with 31 participants comparing Adapalene 0.1% and Benzoyl Peroxide 2.5% gel with a control vehicle, and a larger study with 54 participants comparing Adapalene 0.3% and Benzoyl Peroxide 2.5% gel with a control vehicle.

All three experiments were pre-registered on ClinicalTrials.gov which helps reduce reporting bias. Often there is no incentive or reason to report on data from an experiment if there is no effect.

I’m going to focus on the latter paper as it has the most statistical power (> 80%) and the most clinically relevant results.

In brief, the experiment using Adapalene 0.1% with Benzoyl Peroxide 2.5% gel showed no change in the amount of atrophic scarring after 6 months of treatment, but people using the vehicle control saw an increase in scars (about 2 more scars after 6 months).

In the pilot study with Adapalene 0.3%, participants and investigators saw an improvement in scarring assessments at Week 1 and Week 24.

All three studies found a clinically relevant and statistically significant reduction in acne lesions for those using any Adapalene based gels.

With the Adapalene 0.3% with Benzoyl Peroxide 2.5% gel study, there was a statistically significant improvement in the scar assessment as early as Week 1.

By the end of the experiment at Week 25, there was a 15.5% decrease in a validated scar assessment scale – this worked out to about a mean decrease of 2 acne scars per half of the face.

Participants applied the Adapalene gel to only half of the face and the vehicle control on the other half, the researchers believe that if participants had applied the Adapalene gel to the whole face, there would be a decrease of a mean of about 4 acne scars for the entire face.

For the vehicle control side that contained no Adapalene, participants saw an increase of about 1.5 acne scars at the end of 24 weeks.

In terms of non-validated assessments, the amount of patients who responded to “How visible are the indents or holes to you?” with “A little visible” increased from 37.5% at Week 1 to 62.1% at Week 24.

Because some atrophic scarring can resolve on its own, the researchers believed the decrease in scarring with the Adapalene 0.3% and Benzoyl Peroxide 2.5% gel could be due to an increase in the speed of this resolution. For older scars, they believe that the Adapalene gel could be due to remodelling the dermis of the skin (possibly through stimulation of procollagen), improving their appearance.

Another factor would be the reduction in inflammatory acne lesions which could lead to new atrophic scarring formation.

The researchers point out that scar improvement was seen past 3 months, and that people using Adapalene may consider using the product for longer than 6 adapalene to help improve and prevent the appearance of atrophic scarring

In the US, Adapalene is now available over-the-counter as Differin with Adapalene at 0.1%. If you have moderate-to-severe acne with atrophic scarring you may consider speaking to your doctor and getting a prescription for the stronger 0.3%.

In terms of other retinoids, the researchers point out that there isn’t much research on topical use and improvement in atrophic scarring. For tretinoin I did find two studies, but they included other interventions in combination with the tretinoin. One used iontophoresis to enhance the penetration of tretinoin, and another used tretinoin in combination with microneedling. Both studies found improvement in atrophic scarring. Adapalene and other retinoids activate some of the same receptors, and since topical use of tretinoin has shown to increase procollagen as well, it’s likely that it will provide improvement on atrophic scarring as well.

B. Dreno, J. Tan, M. Rivier, P. Martel, R. Bissonnette, Adapalene 0.1%/benzoyl peroxide 2.5% gel reduces the risk
of atrophic scar formation in moderate inflammatory acne:
a split-face randomized controlled trial, Journal of the European Academy of Dermatology and Venereology (2016), DOI: 10.1111/jdv.14026

M.J. Loss, S. Leung, A. Chien, N. Kerrouche, A.H. Fischer, S. Kang, Adapalene 0.3% gel shows efficacy for the treatment of atrophic acne scars, Dermatology and Therapy (2018), DOI: 10.1007/s13555-018-0231-8

B. Dréno, R. Bissonnette, A. Gagné-Henley, B. Barankin, C. Lynde, N. Kerrouche, J. Tan, Prevention and reduction of atrophic acne scars with adapalene 0.3%/Benzoyl peroxide 2.5% gel in subjects with moderate or severe facial acne: Results of a 6-month randomized, vehicle-controlled trial using intra-individual comparison, American Journal of Clinical Dermatology (2018), DOI: 10.1007/s40257-018-0352-y

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In vivo study of comedone reformation

Using a microscopy technique researchers were able to “watch” what happened to a comedone a week after it was removed.

Previous research has shown that comedones have a cyclical nature, either forming into inflammatory acne, re-appearing, or resolving.

Based on clinical experience, this cycle was estimated to take between 2-6 weeks. However, no studies had been done that provided direct evidence for this timeline.

A week after the comedone was extracted the skin appeared to resolve – to the naked eye. Under a microscope, however, researchers found that dead skin cells and sebum were already beginning to accumulate and reform the comedone.

This highlights the importance of continuing acne treatment even after the skin looks like it has cleared. This may also provide evidence for the use of acne treatments over the entire face or affected area instead of spot treating.

Further research with this technique could show how acne treatments prevent this comedone reformation, if there is individual variation on this reformation, what changes in the skin cells is causing the excess build up, and how long a lesion needs to be treated before the pore returns to normal.

Study finds link between sleep times and sebum production of women’s skin

This paper found a correlation between the time that female subjects went to sleep and how much sebum their skin produced.

A slight increase in sebum production was seen the later they went to sleep. As well, sleeping less was correlated with a slight decrease in sebum production. This relationship wasn’t seen in the male participants of the study.

They also found a correlation between levels of free testosterone and 5α-reductase (an enzyme that converts testosterone in to dihydrotestosterone – a more active form).

Curiously this correlation was, again, only significant for women – despite men having 10 times more free testosterone than women. The researchers think that there may be a maximum threshold for how much testosterone can influence sebum production. There’s also research indicating that the sebaceous gland’s sensitivity to testosterone varies among individuals as well.

While the study’s sample size was quite small, and it’s completely possible this isn’t reproducible, due to random chance or some other variable…there is newer research describing a pathway between inflammation and sebum production – which may be what’s at play here.