Topical combination, physical treatments best for mild-to-moderate acne

Topical pharmacological treatment combinations, chemical peels, and photochemical therapy are deemed to be the best and the most effective options for mild-to-moderate acne vulgaris.

In a meta-analysis of 179 randomized controlled trials (RCTs) with about 35,000 observations across 49 treatment classes, the treatments that showed the greatest effect on total acne lesion count as compared with placebo for patients with mild-to-moderate acne were combined retinoid with benzoyl peroxide (BPO; mean difference [MD], 26.16 percent, 95 percent credible interval [CrI], 16.75–35.36), chemical peels (eg, salicylic or mandelic acid; MD, 39.70 percent, 95 percent CrI, 12.54–66.78), and photochemical therapy (combined blue/red light; MD, 35.36 percent, 95 percent CrI, 17.75–53.08). [Br J Dermatol 2022;doi:10.1111/bjd.21739]

“Oral pharmacological treatments (eg, antibiotics, hormonal contraceptives) did not appear to be effective after bias adjustment, [whereas] BPO and topical retinoids were less tolerated than placebo,” according to the investigators.

For moderate-to-severe acne, on the other hand, the most effective treatments vs placebo were topical combination of retinoid plus lincosamide (clindamycin; MD, 44.43 percent, 95 percent CrI, 29.20–60.02), oral isotretinoin of total cumulative dose ≥120 mg kg⁻¹ per single course (MD, 58.09 percent, 95 percent CrI, 36.99–79.29), light therapy enhanced by a photosensitizing chemical (MD, 40.45 percent, 95 percent CrI, 26.17–54.11), combined BPO with topical retinoid, and oral tetracycline (MD, 43.53 percent, 95 percent CrI, 29.49–57.70). Topical retinoids and oral tetracyclines were inferior to placebo.

Meanwhile, no evidence was identified for hormone-modifying agents (metformin, spironolactone) regardless of acne severity.

“The quality of included RCTs was moderate to very low, with evidence of inconsistency between direct and indirect evidence. Uncertainty in [the] findings was high, in particular for chemical peels, photochemical therapy, and photodynamic therapy. However, conclusions were robust to potential bias in the evidence,” the investigators said.

The present data regarding mild-to-moderate acne vulgaris are consistent with the results of two previous network meta-analyses (NMA). One reported that adapalene combined with BPO was the most effective topical treatment but had a slightly higher incidence of withdrawal than monotherapy. The other found that combined topical retinoids with BPO were the best option, followed by topical antibiotics and BPO. [Br J Dermatol 2021;185:512-525; Front Pharmacol 2020;11:592075]

“A strength of our review and network meta-analyses was the inclusion of a wide range of acne treatments and, subsequently, a much larger number of RCTs (112 for mild-to-moderate and 67 for moderate-to-severe acne) than either of the two previously published NMAs. Furthermore, our NMA assessed treatments for moderate-to-severe acne,” the investigators pointed out.

However, they acknowledged that none of the RCTs included in the present meta-analysis assessed dietary interventions (eg, milk-free diet, low glycaemic load diet) and the effect of treatments on acne vulgaris at body sites other than the face.

In line with the present and previous NMA findings, the National Institute for Health and Care Excellence (NICE) guideline on acne vulgaris management recommends the use of fixed topical treatment combinations (adapalene with BPO, clindamycin with BPO, or tretinoin with clindamycin) as first-line treatment for mild-to-moderate acne, and fixed topical treatment combinations (adapalene with BPO, tretinoin with clindamycin) or oral tetracyclines (doxycycline or lymecycline) combined with topical treatments (fixed combination of adapalene with BPO; or azelaic acid) for moderate-to-severe acne. [https://www.nice.org.uk/guidance/ng198]

“Where oral lymecycline or doxycycline are not tolerated or are contraindicated, alternative oral antibiotics such as trimethoprim or an oral macrolide (eg, erythromycin) might be considered,” according to the investigators.

The choice, they continued, should be shared with the patients after explaining the risks and other characteristics of each treatment and after taking into account the values and preferences of the patients, their history of previous therapy and scarring, their risk of future scarring, and the psychosocial burden imposed by acne.

“BPO alone may be considered as an option across all acne severity levels if other recommended first-line treatments are contraindicated (eg, during pregnancy) or there is a patient preference against their use. Topical retinoids and BPO should be initiated with alternate-day or short-contact application because of their increased risk of discontinuation owing to side-effects,” the investigators said.

Meanwhile, “photodynamic therapy may be considered as an option for adults with moderate-to-severe acne if other treatments are ineffective, not tolerated or contraindicated,” they added.