The new guidelines include 18 evidence-based recommendations and 5 good practice statements resulting from a systematic review conducted by an expert panel. For patients over the age of 9 years, strong recommendations were made for the use of topical therapies such as benzoyl peroxide and retinoids (eg, adapalene, tretinoin, tazarotene, trifarotene), either as monotherapy or combined. Topical antibiotics were also strongly recommended though not as monotherapy. A strong recommendation was made for fixed-dose topical combination therapies as these agents could help with adherence, and in some cases, may be less expensive than prescribing the individual components separately.

With regard to systemic antibiotics, the panel strongly recommended the use of doxycycline and conditionally recommended minocycline and sarecycline based on the available evidence. In general, oral antibiotics should be used concomitantly with benzoyl peroxide and other topical therapies. Limiting the use of systemic antibiotics to the shortest possible duration helps to reduce the development of antibiotic resistance and antibiotic associated complications.

Additional good clinical practices highlighted in the guidelines include the following:

• Intralesional corticosteroid injections may be used as an adjuvant therapy in patients with larger acne papules or nodules.
  • Consider use in patients at risk for acne scarring and for those who need rapid inflammation and pain improvement.
  • Risk of local adverse events may be minimized by using a lower concentration and volume of corticosteroid. 
• Isotretinoin is recommended for patients with severe acne or for those who have failed other oral and topical therapies.
  • Patients with psychosocial burden or acne scarring should be considered candidates for isotretinoin.
  • Monitoring of liver function tests and lipids should be considered in these patients, though complete blood count is not necessary in healthy individuals.
  • Pregnancy prevention is mandatory for patients of childbearing age.

Based on individual patient factors, conditional recommendations were also made for the use of topical clascoterone, topical salicylic acid, topical azelaic acid, and hormone therapies (eg, combined oral contraceptives, spironolactone).

The full report, which also includes information on physical modalities (eg, acne lesion extraction, chemical peels, laser and light-based devices, microneedle radiofrequency devices, photodynamic therapy), complementary and alternative therapies (eg, vitamins, botanical and plant-derived agents) and diet, is available here.

The Food and Drug Administration (FDA) has approved Cabtreo (clindamycin phosphate 1.2%, adapalene 0.15%, and benzoyl peroxide 3.1%) topical gel for the treatment of acne vulgaris in adult and pediatric patients 12 years of age and older.

Cabtreo combines clindamycin phosphate, a lincosamide antibacterial, adapalene, a retinoid, and benzoyl peroxide, an oxidizing agent with bactericidal and keratolytic effects, into one topical gel. The approval of Cabtreo was based on data from 2 placebo-controlled phase 3 studies (Trial 1; ClinicalTrials.gov Identifier: NCT04214639 and Trial 2; ClinicalTrials.gov Identifier: NCT04214652) that included 363 patients 10 years of age and older with facial acne vulgaris.

Study participants were randomly assigned to receive Cabtreo (n=122) or vehicle (n=61) applied once daily for 12 weeks. At baseline, 91% of patients had moderate acne, based on Evaluator’s Global Severity Score (EGSS). The coprimary endpoints were success on the EGSS (defined as at least a 2-grade improvement from baseline and an EGSS score of clear [0] or almost clear [1]), absolute change in noninflammatory lesion count, and absolute change in inflammatory lesion count.

Results from Trial 1 showed that 49.6% of patients treated with Cabtreo achieved EGSS success at week 12 compared with 24.9% of those who received vehicle (treatment difference, 24.7% [95% CI, 10.7-38.7]). In the Cabtreo arm, the mean percent reduction in inflammatory lesions was 75.7% (27.7 mean absolute reduction) vs 59.6% (21.7 mean absolute reduction) in the vehicle arm. Mean percent reduction in noninflammatory lesions was 72.7% (35.4 mean absolute reduction) with Cabtreo and 47.6% (23.5 mean absolute reduction) with vehicle.

Similar results were seen in Trial 2, with 50.5% of Cabtreo-treated patients achieving EGSS success vs 20.5% of the vehicle group (treatment difference, 30% [95% CI, 16.4-43.6]). Mean percent reduction in inflammatory lesions was 80.1% (30.1 mean absolute reduction) with Cabtreo and 56.2% (20.8 mean absolute reduction) with vehicle. Mean percent reduction for noninflammatory lesions was 73.3% (35.2 mean absolute reduction) with Cabtreo and 49.0% (22.0 mean absolute reduction) with vehicle.

The most common adverse reactions reported with Cabtreo were application site reactions, pain, erythema, dryness, irritation, exfoliation, and dermatitis.

The triple combination gel is supplied in 20g and 50g pumps.

According to the new report from the independent laboratory Valisure, benzene “can form at unacceptably high levels” in both prescription and over-the-counter benzoyl peroxide products.

Some tests showed that certain products had more than 800 times the concentration limit for benzene that the US Food and Drug Administration allows.

What triggers the formation of benzene in these treatments?

Tests showed that when stored or handled at high temperatures, such as when left in a hot car for days, they can generate high levels of benzene.

In one test, an acne product was stored at 158 degrees Fahrenheit for nearly 17 hours. The lab not only detected benzene inside the product, but benzene gas found in the air around it was more than 1200 times the threshold that the US Environmental Protection Agency allows for long-term exposure.

Other types of acne treatment products that were tested, such as those containing salicylic acid or adapalene, did not have that issue, according to the lab.

Valisure also sent a citizen petition to the FDA in which it described an initial analysis of 175 acne treatment products, finding that 99 of them contained benzoyl peroxide, with benzene detected in 94 of those products.

The petition urges the FDA to “request recalls and a suspension of sales for products containing the active pharmaceutical ingredient benzoyl peroxide.”

An FDA spokesperson said in a statement Wednesday that it has received the citizen petition, CNN reported.

“The agency acts on information provided from a variety of sources, such as that provided by Valisure, but such data must be verified as accurate and reproducible before it can be utilized to make regulatory decisions such as recommending product sale suspensions and recalls,” the statement said.

Benzene is one of the 20 most widely used chemicals in the US, and people are exposed “mainly by breathing in air containing benzene,” according to the American Cancer Society.

Benzene is also used in a variety of products including lubricants, dyes, detergents and drugs.

This isn’t the first time Valisure has sent a citizen petition letter to the FDA regarding concerns about benzene. In 2022, the lab found benzene in dry shampoo products and urged the FDA to request recalls, and the lab detected benzene in sunscreen in 2021.

But this latest report differs in significant ways, Valisure officials noted.

“This discovery of benzoyl peroxide’s fundamental instability and formation of benzene is substantially different than Valisure’s previous findings of benzene in sunscreens, hand sanitizers and other consumer products,” Valisure co-founder and President David Light said in a statement Wednesday.

“The benzene we found in sunscreens and other consumer products were impurities that came from contaminated ingredients; however, the benzene in benzoyl peroxide products is coming from the benzoyl peroxide itself, sometimes at hundreds of times the conditional FDA limit,” he said. “This means the problem broadly affects benzoyl peroxide products, both prescription and over-the-counter, and necessitates urgent action.”

More information

Visit the National Cancer Institute for more on benzene.

SOURCE: Valisure, news release, March 6, 2024; CNN