Topical agents for acne
When it comes to choosing topical agents for treating acne, separating fact from fiction can be challenging for dermatologists.
“We receive a lot of mixed messages regarding treatments,” says Linda Stein Gold, M.D., director of clinical research for the Department of Dermatology at Henry Ford Hospital in Detroit. “Patients also receive a lot of mixed messages, primarily from the media.”
In an interview with Dermatology Times, following her presentation on topicals at the American Academy of Dermatology (AAD) Acne Boot Camp held in Oralndo, Florida during March 2017, Dr. Stein Gold says there are several “great” topical treatment options to treat anything from mild to severe superficial inflammatory acne.
“Although patients will not achieve results overnight, they generally can see good results by 12 weeks,” Dr. Stein Gold says. “In addition, in most instances, combination therapy is the best approach.”
Early last year, AAD issued new acne treatment guidelines. Among topical therapies, the highest level of evidence is for benzoyl peroxide; topical antibiotics (including clindamycin and erythromycin); combination of topical antibiotics and benzoyl peroxide; topical retinoids (such as tretinoin, adapalene and tazarotene); combination of topical retinoids and benzoyl peroxide/topical antibiotic; azelaic acid; and dapsone.
“I use multiple different regimens of these drugs to individualize patient care,” says Dr. Stein Gold, who dissuades clinicians from using topical antibiotics as monotherapy, due to the development of bacterial resistance. “We should always combine a topical antibiotic with a benzoyl peroxide, which not only increases efficacy but also decreases the potential for bacteria resistance.”
A recent study combining adapalene 0.3% with benzoyl peroxide 2.5% in moderate-to-severe patients found the therapy to be particularly effective in severe patients, even without an oral antibiotic.
“As with any topical retinoid, though, patients can expect to have some local irritation for the first two weeks,” says Dr. Stein Gold, division head of dermatology at Henry Ford Hospital. “Therefore, I generally recommend using the medication on a dry face, applying it every other night, then increasing as tolerated.”
Dr. Stein Gold also reinforces the use of gentle cleansers, a moisturizer and a sunscreen.
Topical dapsone is now available in a 7.5% formulation which is beneficial, as most physicians prescribe it as combination therapy. “Patients had been using the dapsone 5% once daily and not receiving the full efficacy of the BID formulation,” Dr. Stein Gold says.
Medications on the horizon to treat acne include topical minocycline, topical sebum reducers and seracycline.
“Minocycline is a large molecule that is very challenging to deliver topically,” Dr. Stein Gold explains. “It is also very challenging to maintain stability in a topical formulation that is cosmetically acceptable.”
The antibiotic, which is in clinical trials, “appears to be effective and well tolerated,” Dr. Stein Gold says. “It is being studied in both a foam formulation and a gel formulation.”
Minocycline topical gel is a fully solubilized minocycline that is readily bioavailable in a hydrophilic gel and that penetrates directly into the epidermis and pilosebaceous unit.
“The topical gel is also highly lipophilic and miscible with sebum,” Dr. Stein Gold states.
A phase 2 clinical trial of minocycline (FMX010) foam found that after 12 weeks of treatment, minocycline 4% had significantly more subjects with an investigator’s global assessment (IGA) improvement of at least two grades compared to the vehicle group.
Furthermore, the minocycline 4% group had significantly more patients achieving IGA success than the minocycline 1% group and the vehicle groups.
On the other hand, sebum reducers “potentially offer a new mechanism of action to treat acne,” Dr. Stein Gold says. “Thus far, we have not been able to reduce sebum with any topical medicine.”
Olumacostat glasaretil targets acetyl coenzyme-A carboxylase, a key regulator of sebum production, and has shown promise in phase 2 trials.
“SB204, a nitrous oxide-releasing agent, met all of its endpoints in one of two phase 3 clinical trials, but only noninflammatory lesion reduction in a second phase 3 study,” Dr. Stein Gold says.
Seracycline is a new oral antibiotic that has completed phase 3 clinical trials for acne, using weight-base dosing, and is awaiting FDA approval. “Compared to existing tetracycline antibiotics, seracycline has shown improved anti-inflammatory properties and a narrower spectrum of activity,” Dr. Stein Gold reports. Plus, because the drug has weight-based dosing, “efficacy may improve.”
One promising topical antiandrogen in development is crotexolone 17a-propionate, 1% cream, derived from 11-deoxycortisone. The product competes with androgen receptor and is three times more potent than flutamide.
“I believe it is an exciting time in acne therapy,” Dr. Stein Gold observes. “We have a lot of research going on. I think we can expect new treatments in the near future that will help our acne patients achieve better control of their condition.”
Dr. Stein Gold is financially compensated by Galderma, Valeant, Allergan, Dermira and Novan.