Topical Corticosteroids and Topical Calcineurin Inhibitors in Atopic Dermatitis

In the 2024 study by Gether et al., the authors compared the effectiveness of topical corticosteroids (TCS) and topical calcineurin inhibitors (TCIs) in adults with atopic dermatitis (AD).¹ The study assessed AD severity, skin hydration, levels of inflammatory cytokines, and circulating T cells.¹ The findings revealed that while betamethasone was more effective at reducing inflammation, tacrolimus significantly improved skin hydration.¹ 

Background

Atopic dermatitis is a chronic, relapsing inflammatory condition that poses substantial challenges for both patients and providers.¹ First-line treatments for mild AD typically include moisturizers and low-to mid-potency topical corticosteroids (TCS).¹ Escalating treatments can vary, but particularly for more sensitive anatomic areas such as the face, topical calcineurin inhibitors (TCIs) may be used.¹ Despite their widespread use, direct comparisons between the efficacy of TCS and TCIs have been limited.² Previous studies have shown mixed results, with some suggesting that tacrolimus, a TCI, is more effective than weak TCS, while others found pimecrolimus, another TCI, to be less effective.² Given patient concerns about TCS, comparing these treatment options is crucial.²

Study Design and Methods

The study implemented a randomized parallel-group double-blind double-dummy active-comparator study design with 36 participants. This rigorous approach minimized bias by randomly assigning participants to two treatment groups, ensuring neither the participants nor the researchers knew which treatment was administered.¹ The study compared the effects of betamethasone ointment 0.1% (administered once daily with a placebo) and tacrolimus ointment 0.1% (administered twice daily).¹ Natural moisturizing factor (NMF) levels, AD severity, T-cell profiles, and cytokine levels in the skin and blood were measured at baseline, after 2 weeks of daily treatment, and after an additional 4 weeks of twice-weekly maintenance treatment.¹ Participants applied the treatments across the entire body, excluding the face, axillae, and genitals.¹

Results

After 2 weeks, the tacrolimus group showed a statistically significant increase in NMF levels, indicating improved skin hydration, which continued to surpass betamethasone at 6 weeks.¹ Betamethasone, however, was more effective at reducing inflammatory cytokines—such as interleukin (IL) 8, 18, and 22, macrophage-derived cytokine (MDC), matrix metalloproteinase (MMP), and thymus and activation-regulated chemokine (TARC)—at the 14-day mark, with IL-8 and MMP remaining reduced at 6 weeks.¹ Betamethasone also significantly reduced itch intensity and improved sleep quality compared to tacrolimus.¹

Key Takeaways

Tacrolimus was more effective at enhancing skin hydration, while betamethasone excelled in reducing inflammation and improving symptoms in more severe cases of AD. Both treatments were effective for mild-to-moderate AD, but betamethasone showed stronger efficacy in severe cases.

Future Directions and Conclusion

A deeper understanding of how TCS and TCIs function in managing AD could lead to better treatment strategies for this chronic and debilitating condition. Awareness of the strengths and limitations of both treatments will help clinicians tailor therapies to individual patient needs.

Kripa Ahuja reports no relevant financial relationships. Peter Lio, MD, reports research grants/funding from AbbVie, AOBiome; is on the speaker’s bureau for AbbVie, Arcutis, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche-Posay/L’Oreal, MyOR Diagnostics, ParentMD, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, Verrica; reports consulting/advisory boards for Alphyn, AbbVie, Almirall, Amyris, Arcutis, ASLAN, Boston Skin Science, Bristol-Myers Squibb, Burt’s Bees, Castle Biosciences, Codex Labs, Concerto Biosci, Dermavant, Eli Lilly, Galderma, Janssen, Johnson & Johnson, Kimberly-Clark, LEO Pharma, Lipidor, L’Oreal, Merck, Micreos, MyOR Diagnostics, Regeneron/Sanofi Genzyme, Skinfix, Theraplex, UCB, Unilever, Verrica Yobee Care; stock options with Codex, Concerto Biosciences and Yobee Care. In addition, Dr. Lio has a patent pending for a Theraplex product with royalties paid and is a Board member and Scientific Advisory Committee Member of the National Eczema Association.

1. Gether L, Linares HPI, Kezic S, 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. Published online July 30, 2024:jdv.20258. doi:10.1111/jdv.20258

2. Pena J, Zameza PA, Pixley JN, Remitz A, Feldman SR. A Comparison of Topical Corticosteroids and Topical Calcineurin Inhibitors for the Treatment of Atopic Dermatitis. J Allergy Clin Immunol Pract. 2023;11(5):1347-1359. doi:10.1016/j.jaip.2023.03.022