Comparative Effectiveness of Topical Calcineurin Inhibitors in Adult Patients with Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by extreme pruritis and lichenified papules and plaques that may begin in or persist into adulthood. Topical corticosteroids are first-line prescription therapy for AD; they are efficacious and have a well established safety profile. The topical calcineurin inhibitors tacrolimus and pimecrolimus were approved by the US FDA in 2000 and 2001, respectively, as second-line topical therapy for AD. This review evaluates the available studies on the comparative effectiveness, safety, cost, and impact on quality of life of topical corticosteroids and topical calcineurin inhibitors for the treatment of adult AD. Tacrolimus was found to be as effective as class III-V topical corticosteroids for AD of the trunk and extremities, and more effective than low-potency class VI or VII corticosteroids for AD of the face or neck. Pimecrolimus was less effective than both tacrolimus and low-potency topical corticosteroids for moderate to severe AD. The short-term safety studies found that, compared with topical corticosteroid-treated adults, patients treated with topical calcineurin inhibitors had an increased frequency of application-site reactions, an equivalent infection risk, and a decreased risk of skin atrophy. The long-term safety of topical calcineurin inhibitors remains under investigation. Currently published studies that evaluated the comparative cost and quality-of-life effects compared tacrolimus with less potent topical corticosteroids despite the availability of equivalent potency corticosteroids. Further cost and quality-of-life studies are needed that compare topical calcineurin inhibitors with stronger classes of topical corticosteroids over longer time periods. The available clinical trials data do not suggest an efficacy advantage for topical calcineurin inhibitors over topical corticosteroids in adults with AD of the trunk and extremities, and there is not yet adequate evidence to support topical calcineurin inhibitors as first-line therapy for adult AD.

Guidelines of care for the management of atopic dermatitis

“…These symptoms are more frequent than that seen with TCS, but tend to lessen after several applications or when first preceded by a short period of topical steroid use. 96 Patients should be advised of these adverse effects to avoid premature discontinuation of treatment. There are scattered reports of allergic contact dermatitis and a rosacea-like granulomatous reaction due to TCIs.…”

Strategies targeting the IL-4/IL-13 axes in disease

“…Some AD patients experience recurrent bacterial or disseminated viral skin infections such as eczema herpeticum (EH) which can be life threatening [186]. Standard therapies such as emollients and topical steroids are supplemented with calcineurin inhibitors in moderate-to-severe AD patients which are incompletely efficacious in this population [187,188] leaving a clear unmet medical need.…”

Ectoine-Containing Cream in the Treatment of Mild to Moderate Atopic Dermatitis: A Randomised, Comparator-Controlled, Intra-Individual Double-Blind, Multi-Center Trial

“…Since the introduction of topical corticosteroids, they have formed the principal cornerstones of anti-inflammatory therapy in AD [2]. More recently, topical calcineurin inhibitors have been introduced as an alternative, as they provide targeted anti-inflammatory activity without the local or systemic side effects seen with topical corticosteroids [3,4,5]. Although effective, unrestricted and long-term use of glucocorticosteroids and calcineurin inhibitors is hampered by the occurrence of unwanted side effects [reviewed in [6]], indicating the need for alternatives.…”