SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.
In regard to topical treatments, the guidelines make a "strong" recommendation for topical retinoids based on "moderate" evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, at Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks vs those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).
The updated guidelines were published on January 30, in the Journal of the American Academy of Dermatology.The previous guidelines were issued in 2016.
"We have four current retinoids that we use: Adapalene, tretinoin, tazarotene, and trifarotene," Zaenglein said. "Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions."
Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. "I always ask teenage kids about that: Are they using those protein powders?"
Recommendations for 'Multimodal Therapy', Especially With Antibiotics
Zaenglein highlighted a "good practice statement" in the new guidelines that says, "when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action."
Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as "moderate," do not recommend them as monotherapy because of the risk for antibiotic resistance.
The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, "and we also recommend fixed combination products because they're associated with increased adherence."
Dermatologists are familiar with several of these products because "we've been using them for years and years," she said. The guidelines note that "compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72)."
Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has "moderate" evidence regarding preventing the development of antibiotic resistance. "Lower strengths tend to be less irritating, and over-the-counter formulations are readily available," she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.
Now, there's a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.
The new AAD guidelines note that "potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately." The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered "moderate."
Dapsone gel, 7.5% (Aczone) is another option for acne. "It's a topical so you don't need to do G6PD [glucose-6-phosphate dehydrogenase] testing," Zaenglein said. "It's well-tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle," in a 2018 study, which she said also found that females benefited more than males from this treatment.
Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Zaenglein said. She noted that it's the only topical anti-androgen that can be used in males. However, while it has a "high" level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone "may impact equitable acne treatment access." The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube of as ranging from $590 to $671.
"One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy," she said. "Much like other hormonal therapies, it works better over the long term."
Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered "low" for salicylic acid and "moderate" for azelaic acid, the guidelines say, and azelaic acid "may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation."
As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are "preferred" during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should only be used in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is "not recommended."
The recommendations also add that "available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other."
Could BP Post a Risk From Benzene?
Zaenglein highlighted a recently released reportby Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. "They didn't release all of the ones that they evaluated, but there were a lot…that we commonly recommend for our patients," she said.
On March 6, CBS News reported that Valisure "ran tests at various temperatures over 18 days and found some products 'can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene' in 2 weeks at 50° C (122° F)," but that benzene levels "at room temperature were more modest, ranging from about one to 24 parts per million."
Zaenglein said she's not ready to urge patients to discontinue BP, although in light of the findings, "I will tell them to store it at room temperature or lower."
For now, it's important to wait for independent verification of the results, she said. "And then it's up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat."
Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).
Randy Dotinga is an independent medical journalist and board member of the Association of Health Care Journalists.
