Improved Severity of Atopic Dermatitis Achieved With Adjuvant Dupilumab, Tacrolimus

A greater proportion of patients with atopic dermatitis (AD) treated with adjuvant dupilumab and tacrolimus achieved mild disease severity by 1 month of treatment vs patients given dupilumab alone at baseline, according to study findings published in the European Review for Medical and Pharmacological Sciences.

Recent research has indicated that the skin barrier function plays an important role in the etiopathogenesis of AD. Although serving as the first-line topical anti-inflammatory therapy for AD, topical corticosteroids have been associated with significant adverse effects when used chronically and may even cause additional damage to the skin barrier.

Emollient creams, which aim to restore the skin barrier, have been recommended for use among patients even when topical and/or systemic anti-inflammatory treatment is administered.

“Calcineurin inhibitors, including pimecrolimus and tacrolimus, are an alternative to topical steroids, especially for long-term AD stabilization as they do not damage the skin barrier,” noted the study authors. “Available evidence showed that an improved therapeutic response may be obtained with the combination of systemic and topical therapy, both emollient and anti-inflammatory, in the early stages of AD.”

They aimed to further investigate the role of tacrolimus ointment in the management of real-world patients on dupilumab for severe AD. Data from a total of 342 consecutive patients with severe AD treated with dupilumab at the Dermatology Unit, Policlinico of Milan University Hospital, Italy, were retrospectively collected from June 2018 to December 2020. Of this cohort, 307 patients who used both the systemic and topical therapy were eligible for evaluation.

Patient response was measured via the Eczema Area and Severity Index (EASI), itching and sleep Numerical Rating Scale (NRS), and Dermatology Life Quality Index (DLQI) at baseline and after 4, 16, and 52 weeks of treatment with dupilumab.

Among the overall cohort, the mean EASI score of 29.5 at baseline was reduced to 8.4 after 1 month of treatment, 5.0 after 4 months, and 3.2 after 12 months. Significant reductions from baseline were also observed for itching and sleep NRS and DLQI scores.

For the study cohort given the combination threapy, tacrolimus was used by 6.5% (n = 20) of patients at baseline, 11% at 1 month, 13.5% at 4 months, and 11.3% after 12 months. The mean [SD] time to introduce tacrolimus after initiation of dupilumab was 8.3 [0.3] months.

Several factors were correlated with an increased probability to start tacrolimus treatment in association with dupilumab at any time during the study observation:

• female sex (HR, 1.5; 95% CI, 1.1–2.2; P = .034)
• lower DLQI scores (HR, 0.96; 95% CI, 0.94–0.99; P = .011)
• lower age (HR, 0.99; 95% CI, 0.98–0.99; P = .031)
• patients with non-generalized AD vs those with generalized disease (P = .018)

After 1 month of treatment with dupilumab, findings indicated that a higher proportion of patients treated with tacrolimus at baseline achieved a low EASI score (< 7; mild disease) than patients who did not receive tacrolimus at baseline (72.2% vs. 55.8%; P = .027).

“According to our results, the association of tacrolimus with dupilumab is safe and beneficial,” concluded the study authors. “It is mainly useful when initiated early and should be associated with emollients to facilitate the response in localized critical areas.”

Reference

Ferrucci SM, Angileri L, Marzano AV, Berti E, Tavecchio S. Topical tacrolimus during systemic therapy for severe atopic dermatitis in the clinical practice. Eur Rev Med Pharmacol Sci. 2022 Apr;26(7):2518-2523. doi:10.26355/eurrev_202204_28489