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Among nearly 20 different agents and treatment combinations, topical triple-agent fixed-dose combination (FDC) gel emerged as the most efficacious for moderate-to-severe acne.

Researchers who conducted the systematic review and network meta-analysis included 85 studies in their investigation. Topical triple-agent FDC gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments and oral antibiotics (TOA3) consistently ranked in the top three.

The analysis, published in the , was conducted by an international team of researchers based mainly in Canada and the U.S. The following paper excerpts have been edited for length and clarity.

What was the impetus for this investigation?

Guidelines from the U.S., Canada, and Europe recommend topical combination treatments, with consideration of oral drugs, as the first-line approach in moderate-to-severe acne. Topical benzoyl peroxide, topical retinoids, topical antibiotics, and systemic drugs are all effective, but there is a lack of clarity about the most efficacious, researchers wrote.

Four existing systematic literature reviews and network meta-analyses have examined the relative efficacy of numerous acne treatments. Two were specific to patients with mild-to-moderate acne, while the other two included patients with any severity of acne. No prior analysis had addressed patients with moderate-to-severe acne, researchers wrote, despite this subgroup bearing a greater disease and economic burden.

Therefore, the current analysis evaluated the relative efficacy of available treatments for moderate-to-severe acne.

Which treatments were included in the current analysis?

Investigators considered several treatment categories based on American Academy of Dermatology guidelines.

First, researchers included monotherapies including topical (benzoyl peroxide, antibiotics, or retinoids) and oral (antibiotics, retinoids, spironolactones, or contraceptives).

The second category was various combination treatments including topical triple-agent fixed-dose FDC gel, topical double-agent FDCs, pharmacologic and physical treatment combinations, and various other topical and oral therapies.

A third category covered physical treatments alone, including chemical peels, comedone extraction, photothermal and photochemical therapies, photodynamic therapy, photopneumatic therapy, and radiofrequency therapy.

A final category included metformin and combined oral contraceptives.

What were the key findings?

There was a 90% or greater likelihood that triple-agent FDC gel was the most efficacious treatment for each outcome evaluated in the analysis.

TOA3 was numerically superior to triple-agent FDC gel in reducing inflammatory and noninflammatory lesions.

What are the takeaway messages?

The research team concluded that topical triple-agent FDC gel was superior to all treatments for moderate-to-severe acne. Its use makes it possible to reduce the need for oral antibiotics, thereby minimizing the risk of antibiotic resistance.

The findings also suggest that adding an oral antibiotic to double-agent FDC gel does not offer significant benefits compared with triple-agent FDC gel.