Anti-Inflammatory Dose Doxycycline Plus Adapalene 0.3% and Benzoyl Peroxide 2.5% Gel for Severe Acne

September 2019 | Volume 18 | Issue 9 | Original Article | 924 | Copyright © September 2019

Leon H. Kircik MD

Icahn School of Medicine at Mount Sinai, New York, NY

Indiana University Medical Center, Indianapolis, IN

Physicians Skin Care, PLLC; DermResearch, PLLC;

Skin Sciences, PLLC, Louisville, KY

Abstract

Acne is primarily an inflammatory disease. Anti-inflammatory dose doxycycline (40mg: 30mg immediate release and 10mg delayed release beads) is approved for the treatment of rosacea but with demonstrated efficacy for acne. Fixed combination adapalene 0.3% and benzoyl peroxide 2.5% gel is a once-daily formulation approved for the topical management of acne vulgaris. It has both anti-inflammatory and anti-comedogenic properties.

Options for management of severe acne are somewhat limited; many patients are not candidates for or refuse treatment with isotretinoin. Systemic antibiotics may be indicated; acne treatment guidelines emphasize antibiotic stewardship in light of increasing concerns about antibiotic resistance and call for the judicious use of conventional systemic antibiotics. 

This single-center, open label pilot study involving 20 subjects with severe acne assessed the effects of combination treatment using anti-inflammatory dose doxycycline plus adapalene 0.3% and benzoyl peroxide 2.5% gel on IGA scores as well as inflammatory lesion, non-inflammatory lesion, and nodule counts. 

By week 12, 95% of subjects had at least a 2-grade improvement in IGA scores. Reductions in inflammatory and non-inflammatory lesion counts were statistically significant beginning at week 4 and continuing through week 12. By week 4, the percentage of patients with 0 nodules was 70%, compared to baseline of 20%. Further improvements were seen through week 12. Treatment was well-tolerated with no serious treatment-related adverse events.

Combination treatment with anti-inflammatory dose doxycycline plus combination adapalene 0.3% and benzoyl peroxide 2.5% gel is safe and effective for management of severe acne.

J Drugs Dermatol. 2019;18(9):924-927. 

INTRODUCTION

The pathogenesis of acne is complex, comprised of an interplay between androgens, hyperproliferation of keratinocytes, excess sebum production, and P. acnes. It is now understood that acne is primarily an inflammatory disease.1 P. acnes is shown to activate innate immunity via the expression of protease activated receptors (PARs), tumor necrosis factor (TNF) α, and toll-like receptors (TLRs), and the production of interferon (INF) γ, interleukins (IL-8, IL12, IL-1), TNF, and matrix metalloproteinases (MMPs).2

Acne treatment guidelines emphasize the inflammatory nature of the disease, recommending multimodal approaches that target inflammation, address hyperkeratinization, and provide antibacterial effects while incorporating strategies to reduce the risk for bacterial resistance. Guidelines endorse use of topical retinoids and topical benzoyl peroxide for the majority of acne patients, especially those receiving oral antibiotics.3Despite therapeutic advancements, options for management of severe acne are somewhat limited; many patients are not candidates for or refuse treatment with isotretinoin. Systemic antibiotics may be indicated; Guidelines emphasize antibiotic stewardship in light of increasing concerns about antibiotic resistance and call for the judicious use of conventional systemic antibiotics.3

Oracea (doxycycline 40mg: 30mg immediate release and 10mg delayed release beads; Galderma) is an anti-inflammatory agent approved for the treatment of the inflammatory lesions of rosacea.4 In studies of moderate to severe inflammatory acne, doxycycline 40mg had comparable efficacy and superior safety compared to doxycycline 100mg.5 The 40mg dose is below the minimum inhibitory concentration for doxycycline and therefore confers no antibacterial effect. The therapeutic effect is anti-inflammatory only. There is no risk for development of bacterial resistance associated with the use of doxycycline 40mg.