Acne and Treatment Updates

John Barbieri, MD, MBA, is the director of the Advanced Acne Therapeutics Clinic in the Department of Dermatology at Brigham and Women’s Hospital in Boston, MA. A graduate from Perelman School of Medicine at the University of Pennsylvania in addition to a MBA from the Wharton School, Dr Barbieri’s primary focus is on acne, antibiotic stewardship, patient-reported outcomes, and high-value care.

Prior to his session at the Society of Dermatology Physician Assistants 19th Annual Fall Dermatology Conference,¹ Dr Barbieri met with The Dermatologist to discuss his insights into acne and its treatment updates on the horizon.

What are the differences in the role of hormonal therapy between men and women with acne?
One of the most important differences between hormonal therapy for men and women is what patients you can use it in. For instance, with spironolactone, which is a hormonal treatment frequently used for women with acne, about 10% of men will develop gynecomastia if treated with spironolactone. That is a limitation in our ability to use it for male patients. Similarly, combined oral contraceptives are treatment that we really can only use for female patients with acne.

While our systemic antiandrogen treatments can only be used in female patients with acne, there are some topical antiandrogens that are coming out. The most important one is clascoterone, which was recently approved by the FDA. It is a topical antiandrogen that inhibits the androgen receptor in the sebaceous gland, meaning there is less oil production—less food for acne bacteria in the skin—so we see less pimples and manifestations of acne.

Since it's a cream and it only has local effects as it is rapidly metabolized to cortexolone, it is an exciting new development to have a product we can use for both male and female patients for acne.

What updates are there in utilizing topical regimens for mild to moderate acne?
I’ll just go through some of just the general principles of topical treatment. When we think about the pathogenesis of acne, we have issues with pores getting clogged, too much sebum production, oil in the skin, food for bacteria, and more Cutibacterium acnes. C acne is abacteria that is a key player in the disease, and different strains of C acne can predispose people to having acne or not having acne.

For all of those different mechanisms for acne development, we have treatments that can target them. There have been some new treatments over the past few years in each of those pathways. We already touched upon clascoterone, the antiandrogen that helps turn down the sebaceous glands to reduce oil production in the skin and reduce the acne. It is quite effective; when you look at the rates of Investigator Global Assessment success in the clinical trials, clascoterone does about as well as when you look at oral antibiotic trials. Further, a phase 2 study wherein clascoterone was compared with tretinoin revealed it was superior to tretinoin. I think it's going to be a helpful and promising treatment that will complement our other topicals.

We also mentioned bacteria; topical antibiotics are, of course, a mainstay of acne treatment. The classic ones, erythromycin and clindamycin, have been around for decades. We have used those for a long time. New players such as minocycline foam, which is another topical antibiotic, do not have any head-to-head trials with other top antibiotics, so I have no idea if it's better than clindamycin. All I really know is that it's going to be more expensive as a new branded product.

For me, minocycline foam maybe has some use somewhere, but it is not clear to me that it has any obvious advantages over clindamycin. There are certainly some marketing claims that you can make about it. It has a really high concentration, so maybe that has some impact on resistance, but these are all things that are really theoretical and haven't really been shown in well-designed clinical trials. When those comparative effectiveness studies happen, I'll be happy to review that evidence and rethink that position. For me right now, clindamycin is my mainstay, go to, top antibiotic. I don't see that much of a role for minocycline foam right now, other than in some select patients.

On the topical retinoid side, which are our first line topical treatment for acne, we nowo have tretinoin lotion and tazarotene lotion. The idea of both of those is that if we can distribute the retinoid more evenly on the skin, it might lead to less side effects and better efficacy. For tazarotene lotion, they seem to have some data to support that. In phase 2 studies, tazarotene lotion had about half the rate of dryness and other common side effects but similar efficacy to tazarotene cream. Tazarotene lotion does seem to be meeting up that promise of less irritation, but similar efficacy/effectiveness. However, is it worth the difference in cost? That is a decision between the physicians and patients, but certainly it does seem to have those advantages.

Can you describe isotretinoin side effects and how physicians should approach managing them?
Isotretinoin is a really helpful treatment for acne. It is the one treatment we have that’s reliable in improving acne. After a typical 5 to 7 month course of isotretinoin, patients often will have a  durable remission of their acne, which is a unique aspect of isotretinoin.

That is a special property, but it's not without important side effects. The most important one is that it can have harmful effects to a developing fetus. It is a medicine that has to be used cautiously in persons who are of childbearing potential and can become pregnant. We have to think about ways to mitigate that potential risk.

Another common side effect that we run into is dryness. Almost every patient we treat will have dry lips and maybe some dry skin. Even at low doses, dryness happens. Often, we can help manage that using moisturizers or products such as petroleum jelly before different kinds of good, rich emollients on the lips and other areas that get dry.

Through randomized controlled trials, we also know that taking a gram of omega-3 supplementation a day reduces these mucocutaneous side effects by about half. So, omega-3 supplementation is a frequent recommendation I make for my patients to help make isotretinoin more tolerable and reduce that common issue of dryness.

A smaller number of patients will have dry eyes or dry skin in other areas, such as retinoid dermatitis on the arms or hands. These side effects can be managed with topical steroids for the skin or eye drops for the eyes, but they typically are not too hard to address and often get better with time.

The next main set of side effects that we frequently run into are joint symptoms. Joint aches or muscle aches can happen in up to a quarter of patients who are treated at high doses. It is very dose-dependent. An easy way to address the symptoms is to decrease the dose, and another approach we have used is ibuprofen.

A question that often comes up is the issue of growth plates potentially becoming prematurely fused, leading to people who are treated with isotretinoin being shorter. In patients who are treated with years of isotretinoin, we can see some changes to bones, and there have been some reports of premature closure of the growth plates. For acne, however, I don't think that is as much of an issue. We don't seem to see that with short courses. The other thing for me is usually the people who are treated with isotretinoin have pretty severe acne. I know these patients have a higher risk for scarring, and their acne has important consequences for social relationships and psychosocial functioning. If I don't treat someone's acne, those things are still going to be an issue. Because there is a lot of uncertainty and it doesn't seem very likely that isotretinoin is going to cause a meaningful issue in someone's height, for me there really is little to no downside to treating someone with isotretinoin. I think that risk benefit often just goes towards treating the patient given the likely benefit and uncertain to minimal risk of premature growth plate fusion.

We do have other rare side effects with isotretinoin to consider. Patients can get pancreatitis, which is why monitoring lipids comes into play. Interestingly, in patients who get pancreatitis, many of them don't actually have lipid abnormalities, which does call into question this practice. When we've looked at lipids abnormalities, they're extraordinarily rare; less than 1% of patients get elevated triglycerides above 500. There has been a push to reduce ongoing laboratory monitoring for patients on isotretinoin, down to a baseline before they start and then when they are at peak dose.

I still check aspartate aminotransferase and alanine aminotransferase, although the more data we get, the more it seems like those tests really have minimal clinical usefulness. Patients are just as likely to have abnormalities before they started on treatment, which is often a signal of just background noise. I have never seen a report of true lasting hepatic injury for isotretinoin that was clearly associated with the drug. In that way, I think we often end up treating the numbers instead of the patient. I hope it's something that we rethink over time.

Are there any other insights you would like to share with your colleagues on acne vulgaris?
A really important thing is just making sure to understand your patient's lived experience of acne. I think sometimes we can look at people and it can go both ways. We think, "That acne looks really bad," when the patient isn’t actually that bothered by it and vice versa.

We have to make sure we understand that lived experience and that we're tailoring our treatments to our patients’ needs. We also need to think about acne-associated comorbidities and complications, such as depression, acne-associated erythema, or hyperpigmentation darkness, especially in patients with skin of color. Thinking about ways to address those issues in addition to the pimples is crucial as we care for this patient population.   

Reference
Barbieri J. Acne vulgaris. Presented at: Society of Dermatology Physician Assistants 19th Annual Fall Dermatology Conference; November 4-7, 2021; Los Angeles, CA.