Daily Application of Fluocinonide 0.1% Cream for the Treatment of Atopic Dermatitis

Objective: To assess the efficacy and safety of topical fluocinonide 0.1% cream for the treatment of atopic dermatitis. Design: In this double-blind, vehicle-controlled study, patients were randomized to receive treatment with fluocinonide 0.1% cream applied once (n=109) or twice daily (n=102) or vehicle applied once (n=50) or twice daily (n=52) for two weeks. Setting: Multicenter, outpatient. Participants: Patients aged 18 years or older with atopic dermatitis affecting at least two percent but less than 10 percent of body surface area. Measurements: Efficacy and safety measures included lesion severity, pruritus, hypothalamic-pituitary-adrenal axis suppression, and adverse events. Results: Fluocinonide 0.1% cream applied once or twice daily was more effective than cream vehicle. Both regimens were similarly efficacious after two weeks of treatment. At the end of treatment, lesions were cleared or almost cleared in 59 percent of subjects treated once daily and 57 percent of subjects treated twice daily with fluocinonide 0.1% cream. Further, considerable residual benefit remained after cessation of twice-daily versus once-daily treatment. Skin safety evaluations showed no significant adverse effects of treatment on signs or symptoms of skin atrophy. Fluocinonide 0.1% cream and vehicle treatments did not differ significantly in their suppression of the hypothalamic-pituitary-adrenal axis, nor did hypothalamic-pituitary-adrenal axis suppression differ significantly following once- or twice-daily treatment with fluocinonide 0.1% cream. Fluocinonide 0.1% cream was well tolerated. Conclusion: Once- or twice-daily topical application of fluocinonide 0.1% cream for 14 days was safe and effective for treating atopic dermatitis in this adult patient population. The efficacy of once-daily application was comparable to twice-daily application.Atopic dermatitis is a chronic disease with acute flare-ups and periods of remission. It is often the first manifestation of a group of allergic disorders that includes asthma, allergic rhinitis, and food allergy.^1,2 Both genetic and environmental factors influence development of the disease.³ Approximately 10 to 20 percent of children and 1 to 3 percent of adults are diagnosed with atopic dermatitis.² The disease develops during the first 12 months of life in 75 percent of children who are affected and clears completely at, or shortly after, puberty in 40 to 60 percent^4,5; however, atopic dermatitis may persist in more than 20 percent of adolescents, and up to 17 percent of adults may experience the onset of atopic dermatitis after adolescence.^6,7The clinical presentation of atopic dermatitis varies with age and disease activity.^2,5,8,9 In children between two years of age and puberty, the exudative lesions observed in infancy are less common.^2,9 Rather, lesions tend to be more chronic and characterized by severe pruritus with excoriations and lichenified papules and plaques and involve the hands, feet, wrists, ankles, and antecubital and popliteal regions.^2,5 After puberty and continuing into adulthood, main areas of involvement include the flexural folds; face and neck; upper arms and back; and the dorsa of the hands, feet, fingers, and toes.^2,5 Dry, scaling, erythematous papules and plaques are characteristic, and large lichenified plaques are formed as the lesions become more chronic.^2,5 Although weeping, crusting, and exudation may occur, these findings are usually due to staphylococcal skin infection.⁵Managing atopic dermatitis requires a multifactorial approach that includes regular use of emollients and skin hydration, antipruritic therapy, topical anti-inflammatory agents, identification and elimination of possible triggers, and systemic antibiotic treatment if widespread secondary bacterial infection, mainly due to Staphylococcus aureus, is present.^2,9 For more than 40 years, topical corticosteroids have been a key component of the management of atopic dermatitis¹⁰ and continue to be important agents, particularly for the control of acute flare-ups.⁹ In addition to their anti-inflammatory effect, the use of topical steroids reduces skin colonization with S. aureus.^9,11Topical corticosteroid formulations ranging from low potency to super potency are available.⁵ Recent guidelines recommend using low- to mid-potency topical corticosteroids for the treatment of mild-to-moderate atopic dermatitis and more potent preparations for moderate-to-severe disease and for patients with lichenified plaques.⁹ The general rule has been to use the least potent, most effective topical corticosteroid for the treatment of atopic dermatitis. A possible disadvantage of using a lower-potency preparation initially is that this may fail to improve or even worsen the disease, resulting in poor treatment adherence.¹² An emerging strategy is to “hit hard and hit fast” by initiating treatment with a mid- or high-potency topical corticosteroid (except for lesions on the face, axillae, or groin) to gain rapid control of the disease, and then maintain improvement with a low-potency preparation, or to use a potent preparation intermittently (e.g., twice weekly or two consecutive days each week) to reduce flares.^12,13The optimal dosage frequency of topical corticosteroids in atopic dermatitis has not been fully evaluated and remains unclear^14,15; however, twice-daily (BID) application, the most commonly recommended regimen based on approved product labeling of many topical corticosteroids, has evolved empirically over time.^14,15 Frequency of application is an important clinical consideration, as it is likely to be a major factor influencing patient adherence to treatment. Data from 76 studies indicate that the rate of adherence with BID dosing is lower than with once-daily (QD) dosing (69% vs. 79%).¹⁶ A recent systematic review of the literature comparing QD versus BID application of topical corticosteroids identified only seven randomized, controlled trials of the same active compound and three comparing different agents of the same potency that met the inclusion criteria of the review.¹⁴ It was concluded that the efficacy of the same potency topical corticosteroids used QD and BID was similar and did not favor one regimen over another¹⁴; however, an earlier, similar systematic review concluded that, in the absence of clear evidence from randomized, controlled trials to support BID over QD topical corticosteroid application, initiating therapy in all patients with a QD regimen would be reasonable.¹⁰ It was also noted that the vehicle used in the topical formulation may enhance efficacy, and that when two treatments are equally effective, the cosmetic acceptability of one vehicle over another may facilitate long-term use.¹⁰Fluocinonide 0.1% cream, a super-potent topical corticosteroid, is currently available in the United States. Although this formulation contains a two-fold higher concentration of fluocinonide than what is found in earlier products (0.05%), the vehicle characteristic of the cream allows for marked retention of the active ingredient in the stratum corneum, epidermis, and dermis, with a lesser propensity for systemic absorption.¹⁷ Additionally, the cream vehicle is similar to a conventional ointment base in that its water content is very low (<1%); however, it is devoid of the greasiness of an ointment.¹⁷ Similar to the other available super-potent topical corticosteroids, with the exception of clobetasol propionate 0.05% formulations, fluocinonide 0.1% is approved for QD or BID application.¹⁸The following Phase 3 clinical trial was undertaken to evaluate the efficacy and safety of fluocinonide 0.1% cream compared to vehicle when applied topically QD or BID for two weeks for the treatment of adults with atopic dermatitis.