Tretinoin microsphere gel in younger acne patients

Journal of Drugs in Dermatology, August, 2008 by Joseph Jorizzo, Rachel Grossman, Marge Nighland

ABSTRACT: Background: Facial acne is common in adolescents and can have a significant psychosocial impact. Treatments prescribed should not add stress by causing excessive localized irritation.

Objective: To determine whether the lowest concentration of tretinoin microphere gel (TMG) currently available (0.04%) provides an acceptable balance of efficacy and tolerability for adolescents with moderate facial acne.

Methods: The findings of 2 multicenter, randomized, double-blind, vehicle-controlled trials of TMG 0.04% applied once nightly for 12 weeks in 245 adolescents ages 11 to 16 years with moderate facial acne were combined. Patients were evaluated via changes in acne lesion counts and the occurrence of cutaneous and other adverse effects.

Results: Tretinoin microsphere gel 0.04% reduced total, noninflammatory, and inflammatory lesion counts to a significantly greater extent than the vehicle gel at 12 weeks (P < .000005). The mean percentage reductions in noninflammatory and inflammatory lesion counts at 12 weeks in females were 45.0% and 51.4% and 51.4%, respectively; and in males, 20.5% and 36.7%, respectively. Tretinoin microsphere gel 0.04% was tolerated well, with over 70% of patients experiencing no cutaneous adverse events (AEs).

Conclusion: Tretinoin microsphere gel 0.04% is effective in significantly reducing all types of acne lesions in adolescents with moderate facial acne ages 11 to 16 years, and has a low incidence of cutaneous AEs.

INTRODUCTION

Facial acne is common in adolescents and is estimated to affect more than 80% of this age group. (1), (3) Because self-image is of singular importance in this population, acne can have a significant psychosocial impact, and its consequences include embarrassment, anxiety, and social inhibition. (3-7) For those with mild to moderate facila acne, a wide variety of topical medications are available for treatment including retinoids such as tretinoin (all-trans retinoic acid), the clinical efficacy of which is well established. (8-12) Tretinoin acts by both comedolysis and the normalizing maturation of the follicular epithelium such that comedone formation is decreased, progression to larger or inflammatory lesions is prevented, (12), (13) and substantial clinical improvement is usually seen within 6 weeks of instituting topical tretinoin therapy. (12) Successful treatment of acne in adolescents has been found to be accompanied by improvements in the personal and social consequences of the condition. (4)

Tretinoin, as with other topical retinoids, has the potential to cause localized irritation ("tretinoin dermatitis"), which may manifest as a mild pustular flare after 1 to 2 weeks of use. (12), (13) In a small percentage of patients, this adverse effect may limit the success of tretinoin therapy because it may be as deleteriouts to self-image as the condition itself, and compliance with treatment may be compromised. In an effort to minimize this treatment-limiting response, while maintaining clinical efficacy, tretinoin has been formulated in sponge-like polymeric microspheres that encapsulate the active ingredient and deliver it gradually and selectively to the follicle. (12), (14) In comparison with a standard 0.025% cream, a tretinoin microsphere gel (TMG) 0.1% formulation has been shown to be less irritating to normal skin (15) and to cause significantly less erythema and dryness. (16)

This investigation in 11-year-old to 16-year-old patients with moderate facial acne was undertaken to determine whether the lowest concentration of tretinoin currently available in a microsphere gel formulation (0.04%) provides an acceptable balance of efficacy and tolerability for adolescents. To assess this, the safety and efficacy results of 2 multicenter, randomized, doubleblind, vehicle-controlled studies were combined.

METHODS

The 2 randomized, double-blind, parallel-group studies were conducted at 21 centers in the US, 12 of which participated in both. The second study (24100.11) began after the completion of the first (23333.11DR). The trials satisfied the criteria for adequate and well-controlled studies as defined by the Food and Drug Administration (FDA) Code of Federal Regulations (Title 21; Part 314.126). (17) Written informed consent was obtained from all patients prior to the performance of any study procedures.

In the 2 studies, a total of 561 patients ages 11 to 49 years with moderate facial acne were treated once nightly with either TMG 0.04% (Retin-A Micro[R]gel), TMG 0.06%, or the vehicle gel (placebo) for 12 consecutive weeks. The present analysis was restricted to those ages 11 to 16 years who received either TMG 0.04% (n=126) or the vehicle gel (n = 119); results for the TMG 0.06% formulation and patients ages 17 to 49 years were not included.

Patients and Treatment

Patients enrolled in the 2 studies were required to have moderate facial acne with Cunliffe scale scores (18) between 1.0 and 4.0, total facial lesion counts between 20 and 150, noninfalmatory lesion counts (comedones, open and closed) between 10 and 100, inflammatory lesion counts between 10 and 50, and no more than 2 nodules. Other key inclusion/exclusion criteria were: no treatment with systemic retinoids in the previous year or topical retinoids within the previous 30 days; no systemic antibiotics known to affect the course of acne, new antihista mines, or systemic corticosteroids within the previous 30 days; no topical medications of any type applied to the face within the previous 2 weeks or any emollients or cosmetics on the day of pre-study evaluations. Females who were pregnant, nursing, or of childbearing potential and not using an approved contraceptive method were excluded as were patients with a score of >2 for cutaneous signs and symptoms (eg, erythema, peeling, dryness, burning/stinging, or itching), excessive facial hair, or evidence of any other skin condition that might require concurrent therapy or confound the safety/efficacy evaluation of the trial medication.