Topical Betamethasone Versus Tacrolimus Ointment: Atopic Dermatitis Severity Reduction

Lise Gether

Credit: ResearchGate

Treatment of atopic dermatitis with topical betamethasone and tacrolimus ointment both were effective in reducing disease severity, new findings suggest, though betamethasone is more effective in lowering inflammation and tacrolimus in improving skin hydration.¹

This new research was led by Lise Gether, from the Copenhagen Research Group for Inflammatory Skin (CORGIS) at the University of Copenhagen Herlev-Gentofte Hospital in Denmark. Gether et al. sought to compare betamethasone 17-valerate 0.1% and tacrolimus 0.1% ointment as topical options for patients with atopic dermatitis.

Specifically, the team compared the topicals’ impact on adults with eczema in terms of function of the skin barrier and inflammatory biomarkers in skin and blood. Despite their acknowledgement of the reliability of thymus and activation-regulated chemokine (TARC) as an individual biomarker, Gether and colleagues noted that a biomarker panel would likely correlate better with disease severity versus only 1 biomarker.²

“As previously reported, the primary objective of the study was to compare possible diabetogenic effects of these treatments, where we found that topical betamethasone led to systemic exposure but did not compromise glucose metabolism during short-term use,” Gether and colleagues wrote. “In this article we present secondary predefined endpoints including cutaneous and systemic biomarker responses.”¹

Trial Design

The research team conducted the randomized, double-blind, parallel-group, double-dummy, active-comparator clinical study, assigning individuals with atopic dermatitis to either be given a once-per-day application of betamethasone 17-valerate 0.1% (a corticosteroid) and a placebo vehicle, or to twice-per-day applications of tacrolimus 0.1% (a calcineurin inhibitor).

Both of these 2 cohorts were given a whole-body treatment, though the face, axillae, and genitals were excluded by the investigators. Prior to beginning treatment, trial participants were included in a 2-week washout period. This transpired without topical anti-inflammatory treatments or UV therapy, though emollients were an exception to the former.

The research team’s main endpoint focused on insulin sensitivity, and their secondary endpoints included severity of atopic dermatitis, skin barrier status, systemic corticosteroids and calcineurin inhibitor exposure, and cutaneous and systemic inflammation levels.

Individuals in the age range of 18-75 years were included if they had disease duration of more than 3 years, eczema of any severity, and no systemic treatments for the skin disease within 4 weeks before the research began. Exclusion criteria encompassed chronic inflammatory diseases (except stable rhinitis and asthma), pregnancy, breastfeeding, and systemic anti-inflammatory treatments.

The research team evaluated eczema severity, gathering blood and tape samples over the course of 3 visits: the point of baseline, following 2 weeks of treatment each day, and then following 4 weeks of twice-per-week maintenance treatment.

The team evaluated patient burden through the use of the Dermatology Life Quality Index (DLQI) and Patient-Oriented Eczema Measure (POEM) questionnaires, and they evaluated disease severity through the Eczema Area and Severity Index (EASI). Sleep disturbances and pruritus intensity over the prior week were assessed through a visual analogue scale (VAS).

A total of 36 adult subjects with atopic dermatitis who had been treated with either the topical corticosteroid or the calcineurin inhibitor were included. The investigators evaluated severity of disease, cytokines in the skin and blood, natural moisturizing factor levels, and circulating T cells at baseline, after two weeks of daily treatment, and after 4 weeks of maintenance therapy.

Study Findings

The research team concluded that mean severity of the atopic dermatitis at the point of baseline corresponded to moderate disease and was shown to drop significantly among both the betamethasone and tacrolimus cohorts. The team did, however, report that natural moisturizing factor levels rose significantly with those given tacrolimus after 2 weeks of therapy (P = .002).

Natural moisturizing factor levels tended to be greater than those given betamethasone at the 6-week mark (P = .06). They also expressed that skin cytokines had decreased among both cohorts.

Additionally, the investigators noted that IL-8, IL-22, IL-18, MDC, IP-10, MMP-9, and TARC were found to have decreased more with betamethasone versus tacrolimus following 2 weeks, though this was only true after 6 weeks for IL-8 and MMP-9. They found that around half of the systemic cytokines dropped significantly after using both therapies, though betamethasone led to decreased MDC significantly more following 2 weeks.

Slight differences were reported by the research team in the expression and activation of T cells between groups, according to their T-cell characterization analyses.

“In conclusion, topical treatment of (atopic dermatitis) with betamethasone and tacrolimus ointment effectively reduced disease severity along with reduction of cutaneous and systemic inflammatory markers,” they wrote. “Tacrolimus improved the skin NMF levels more than betamethasone.”

References

1. ^{Gether L, Linares HPI, Thyssen JP, et al. Skin and systemic inflammation in adults with atopic dermatitis before and after whole-body topical betamethasone 17-valerate 0.1% or tacrolimus 0.1% treatment: A randomized controlled study. J Eur Acad Dermatol Venereol. 2024 Jul 30. doi: 10.1111/jdv.20258. Epub ahead of print. PMID: 39078120.}
2. ^{Thijs JL, Nierkens S, Herath A, Bruijnzeel-Koomen CAF, Knol EF, Giovannone B, et al. A panel of biomarkers for disease severity in atopic dermatitis. Clin Exp Allergy. 2015; 45: 698–701.}