Efficacy and Safety of Adapalene 0.3%/Benzoyl Peroxide 2.5% Gel Plus Oral Doxycycline in Subjects With Severe Inflammatory Acne Who Are Candidates for Oral Isotretinoin

March 2018 | Volume 17 | Issue 3 | Original Article | 264 | Copyright © March 2018

James Q. Del Rosso DO,a Linda Stein Gold MD,b Sandra Marchese Johnson MD FAAD,c Maria Jose Rueda MD,d Hilary Baldwin MD,e Edward L. Lain MD,f Megan Landis MD,g Marta Rendon MD,8 Emil Tanghetti MD,9 and Jonathan Weiss MD10

aJDR Dermatology Research/Thomas Dermatology, Las Vegas, NV bHenry Ford Medical Center, Department of Dermatology, Detroit, MI cJohnson Dermatology, Fort Smith, AR dGalderma Laboratories, L.P., Fort Worth, TX eThe Acne Treatment and Research Center, Morristown, NJ fAustin Institute for Clinical Research, Pflugerville, TX gDermatology Specialists Research, New Albany, IN hRendon Center for Dermatology and Aesthetic Medicine, Boca Raton, FL iCenter for Dermatology and Laser Surgery, Sacramento, CA jGwinnett Clinical Research Center, Snellville, GA

INTRODUCTION: Acne treatment guidelines suggest a combination approach with topical therapy including a topical retinoid, benzoyl peroxide and an oral antibiotic, or oral isotretinoin (OI), as first-line treatment options for severe acne vulgaris (AV). This study evaluated the efficacy and safety of a daily regimen of 0.3% adapalene and 2.5% benzoyl peroxide (0.3% A/BPO) gel and oral doxycycline 100 mg twice daily in severe (nonnodulocystic, non-conglobate) inflammatory AV. METHODS: This was a phase 4, 12-week, single-arm, openlabel, multi-center investigational study. Subjects (males and females, 12 or older, with severe inflammatory AV, Investigator Global Assessment [IGA] 4, and less than equal to 4 nodulocystic lesions, n=186) were considered OI candidates at baseline by the investigator. OI candidacy was re-evaluated at each study visit. Efficacy endpoints included inflammatory lesion (IL) reduction (week 12), IGA success (defined as IGA 0 [Clear] or 1 [Almost Clear], weeks 4, 8, and 12), percent reduction in lesions (weeks 4, 8, and 12), and subject questionnaires (week 12). Safety assessments included adverse events (AEs) and tolerability. RESULTS: Mean IL counts were significantly reduced from baseline to the end of the study (mean [SD]; baseline, 44.8 (21.73); week 12, 14.8 (16.11); mean percent reduction, 66.2% [30.47]; P less than .0001). By week 12, 37.1% of subjects achieved IGA Success (n=69, P less than .0001). Most subjects self-reported at least moderate improvement in AV (90.2%), and were “Satisfied” or “Very Satisfied” with the study treatment overall (83.2%). 41.9% of the subjects were no longer considered by their investigator to be OI candidates at week 4. At 12 weeks, only 19.9% were still considered OI candidates. CONCLUSION: 0.3% A/BPO + DOX is an effective and safe treatment option for severe inflammatory AV, before starting OI treatment, or as an alternative when OI cannot be used. ClinicalTrials.gov identifier: NCT02899000

J Drugs Dermatol. 2018;17(3):264-273.


Acne vulgaris (AV) is a common, chronic, inflammatory disorder that usually starts in early adolescence (ultimately affecting approximately 85% of adolescents); however, AV can occur at any age and persist well into adulthood.1-4 The consequences of AV may include physical (eg, skin discomfort/pain, erythema, hyperpigmentation, scarring), psychological (eg, anxiety, poor self-esteem, depression, suicidal ideation), and social repercussions (eg, avoidance of interpersonal interactions).5-10 The incidence of severe AV typically increases throughout adolescence, and the severity of both physical and psychosocial sequelae tend to increase as AV severity worsens.11,12 Thus, a need exists for efficacious, well-tolerated, and safe therapies for severe AV. Furthermore, optimal AV treatment may be delayed if affected individuals do not seek or obtain treatment appropriate for their severity of AV. Current guidelines for severe AV recommend a rational combination therapy regimen (eg, topical agents [retinoid, benzoyl peroxide] and an oral antibiotic); oral isotretinoin (OI) is also a