Efficacy and Safety of Subantimicrobial Dose, Modified-Release Doxycycline 40 mg Versus Doxycycline 100 mg Versus Placebo for the treatment of Inflammatory Lesions in Moderate and Severe Acne: A Randomized, Double-Blinded, Controlled Study
June 2015 | Volume 14 | Issue 6 | Original Article | 581 | Copyright © June 2015
Angela Moore MD,a Mark Ling MD,b Alicia Bucko MD,c Vasant Manna MD,d Marie-Jose Rueda MDe
aArlington Research Center, Arlington, TX; Baylor University Medical Center, Dallas TX, University of Texas;
bMedaPhase, Inc., Newnan, GA
cAcademic Dermatology Associates, Albuquerque, NM
dGalderma R&D Inc., Princeton, NJ
eGalderma Laboratories, L.P., Fort Worth, TX
INTRODUCTION: Routine use of doxycycline (DC) 100 mg for the treatment of moderate to severe acne may be associated with gastrointestinal
adverse events (AEs), thus potentially impacting patient adherence, and antibiotic resistance. This study evaluated the safety and efficacy of subantimicrobial, modified-release (MR) DC 40 mg compared to DC 100 mg and to placebo for the treatment of inflammatory lesions in moderate and severe acne.
METHODS: 662 subjects aged 12 years or older with moderate to severe acne received subantimicrobial, MR-DC 40 mg tablets, DC 100 mg capsules, or placebo once daily for 16 weeks.
RESULTS: MR-DC 40 mg was superior to placebo in the mean reduction of the number of inflammatory lesions, median percent reduction in inflammatory and total lesions, and success rate. MR-DC 40 mg was also comparable to DC 100 mg in the reduction of the number of inflammatory lesions, and percent reduction of total lesions. Incidence of drug-related AEs for MR-DC 40 mg was similar to placebo and was markedly smaller compared to DC 100 mg.
DISCUSSION: MR-DC 40 mg demonstrated comparable efficacy and superior safety to DC 100 mg in the treatment of moderate to severe inflammatory acne. J Drugs Dermatol. 2015;14(6):581-586.
Acne is a chronic inflammatory disease of the pilosebaceous
unit with serious physical and psychological sequelae. 1,2 It is one of the most prevalent skin conditions affecting nearly all people aged 15–17 years, with an estimated prevalence rate of 85% in those aged 12–24 years.2-5 Moreover, the prevalence of acne in adults remains high.6
Clinical features include noninflammatory lesions (open and closed comedones), inflammatory lesions (papules and pustules)
and scarring, postinflammatory hyperpigmentation in certain populations, as well as nodules in severe nodulocystic
acne.7 Mechanisms responsible for the development of acne include androgen-induced seborrhoea, altered keratinization
process, bacterial proliferation by Propionibacterium acnes and inflammation.7,8
Tetracyclines such as doxycycline (DC) are routinely used at antibacterial
doses (50-200 mg daily) and for a prolonged period of time for the treatment of moderate to severe acne. However, routine
use may be associated with patient safety and public health issues, such as antibiotic resistance even after only 1 week of antibiotic
usage.9-11 Tetracyclines are known to have both antibiotic and anti-inflammatory activity.12 In contrast to traditional antibiotic
therapy, targeting inflammation in acne with subantimicrobial doses of DC may be less prone to development of bacterial resistance. 12 In the United States, low-dose modified-release (MR) DC is approved for the treatment of inflammation associated with rosacea,
a disease that does not implicate bacteria in the pathology.1 A number of studies in rosacea have demonstrated the anti-inflammatory
activity of tetracyclines, both with antibiotic doses of tetracyclines and DC 40 mg (MR-DC without antibiotic activity).13-19
Clinical evidence has suggested that subantimicrobial doses of MR-DC may have the potential to treat inflammatory lesions of acne.20-24 The mechanism of action is probably through inhibition
of the pro-inflammatory mediators associated with the