A Meta-analysis to Investigate the Relation Between Fitzpatrick Skin Types and Tolerability of Adapalene-Benzoyl Peroxide Topical Gel in Subjects with Mild or Moderate Acne

The overall goal of acne management for all patients is to select treatments that effectively address as many pathogenic factors as possible while minimizing side effects. Acne therapy in darker skin patients presents unique challenges due to differences in the risk of postinflammatory hyperpigmentation, which may develop in response to acne itself or to irritation secondary to treatment. One combination treatment currently available is a gel formulation containing a retinoid (adapalene 0.1%) in fixed combination with an antimicrobial (benzoyl peroxide 2.5%). Results from three randomized, double-blind, vehicle-controlled, clinical trials of adapalene-benzoyl peroxide were combined in a retrospective meta-analysis that included 909 patients treated for 12 weeks and assessed at each visit for erythema, scaling, dryness, and stinging/burning. Only Week 1 results were included in the meta-analysis because the worst severity of cutaneous irritation was found to occur at this timepoint in all three trials. For each study, and for the meta-analysis, comparisons were made using the Cochran-Mantel-Haenszel test. There were no statistically significant differences in dryness, scaling, and stinging/burning with adapalene-benzoyl peroxide treatment when subjects with Fitzpatrick skin types I to III were compared to subjects with Fitzpatrick skin types IV to VI (P=NS). Erythema assessments were statistically different based on skin types, as subjects with Fitzpatrick skin types IV to VI were rated as having “none” more often than those with Fitzpatrick skin types I to III (P<0.001). This could be due to the difficulty in visualizing erythema in patients with darker skin types, mainly Fitzpatrick skin types VI. Acne patients with Fitzpatrick skin types IV to VI were not found to be more susceptible to cutaneous irritation from treatment with the adapalene-benzoyl peroxide gel than patients with Fitzpatrick skin types I to III.Acne affects individuals of all races and ethnicities. The pathogenesis of acne is multifactorial, and the same factors are probably involved across the spectrum of skin types: sebaceous follicle obstruction, excessive sebum production due to hormonal stimulation of sebaceous glands, and proliferation of Propionibacterium acnes, which produces chemotactic factors and proinflammatory mediators that, in turn, generate an inflammatory response, followed by follicular rupture and extension of inflammation into the dermis, resulting in the formation of inflammatory lesions.^1,2The overall goal of acne management in all patients is to select treatment that effectively addresses as many of the pathogenic factors as possible while minimizing side effects.^3,4 Using multiple agents at the same time during treatment (concomitant therapy) has been recommended as a rational means to achieve this goal.^5,6 Acne therapy in skin of color (high melanin content) presents unique challenges due to differences relating to acne sequelae in these skin types, especially the presence or risk of postinflammatory hyperpigmentation (PIH) and keloidal scarring,^7–10 which are more prevalent in darker skin.^11–13Current acne treatment recommendations include combining gentle cleansing, effective moisturization, and sun protection, along with lower concentrations of benzoyl peroxide (BPO, 2.5%, 5%) and topical retinoids (adaplene 0.1%, tretinoin microsphere 0.04%, tazarotene 0.05%).^6,7,14 These agents can then be titrated up to higher concentrations if tolerated by the patient. Recently, a fixed-dose combination product containing a retinoid (adapalene) in combination with an antimicrobial (BPO) became available. Retinoids, such as adapalene, tretinoin, and tazarotene, are ideally suited for acne therapy because they target key factors in hyperkeratinization and comedogenesis, and are anti-inflammatory.¹⁵ Adapalene itself possesses anticomedogenic, comedolytic, and anti-inflammatory properties.^16–19 Some studies have documented that retinoids in skin of color, in addition to effectively treating noninflammatory and inflammatory acne, may also improve PIH.^20–23 Antimicrobials, such as BPO, provide additional benefits. BPO is an oxidizing agent with antibacterial and keratolytic effects and is used in acne treatment for its activities in decreasing the bacterial population of P. acnes.^24–27 In addition, the nonclinical and clinical safety profile of BPO is well established.²⁸Despite the benefits of combination therapy, the potential for increased cutaneous irritation is a concern. Although it has not been established that skin of color is more or less sensitive to irritants,²⁹ PIH may be triggered in darker skinned patients by skin irritation independent of cause (i.e., a disease or iatrogenic cause).^11,21,30 This issue has led some physicians to believe that skin of color is more sensitive to irritation from therapy. Because acne-related PIH is caused by a response to skin inflammation,^7,8 minimizing inflammation and reducing potential irritation and dryness is also a key goal in treating acne in skin of color. This is why dermatologists who treat acne patients with darker skin strive for a balance between effectively treating acne lesions and recognizing the importance of tolerability.This meta-analysis of the cutaneous irritation of adapalene-BPO gel was conducted to investigate possible differences in the incidence and severity of irritation among patients with different skin types. Three randomized, double-blind, vehicle- and placebo-controlled, clinical trials involving 3,855 patients have established the safety and efficacy of adapalene-BPO gel in the treatment of acne for all skin types.^31–33 The present retrospective meta-analysis is based on the tolerability data from those patients who were assigned to the adapalene 0.1%–BPO 2.5% treatment arm in each of the three randomized trials.