Andreas Wollenberg

Credit: ResearchGate

Baricitinib treatment of atopic dermatitis (AD) may lead to lasting enhancements in clinical signs of inflammation and excoriation specifically, according to new findings, suggesting that targeted inhibition of janus kinases (JAK)-1 and 2 can effectively provide relief from inflammation and itch.¹

These findings were the results of a recent post-hoc analysis designed to assess baricitinib’s impact on the subscores of Eczema Area and Severity Index (EASI) such as erythema, edema/papulation, excoriation, and lichenification. The new research was led by Andreas Wollenberg and Dagmar Simon, from Ludwig Maximilian University of Munich and the University of Bern, respectively.

The investigators noted that although baricitinib has shown efficacy in its enhancement of EASI total scores, covering both severity and body surface area (BSA), there was not conclusive evidence on whether inhibition of inflammatory and itch-mediating cytokines with this drug may lead to improvements across all 4 cutaneous signs which EASI is used to examine.^2,3

“Therefore, in this post-hoc analysis, we aim to examine the effect of baricitinib on each individual EASI sign subscore, thereby elucidating the effect of JAK1/2 inhibition on acute and chronic signs of AD linked to inflammation and/or itch-induced scratching,” Wollenberg, Simon, and colleagues wrote.

Background

The investigators described the background of the baricitinib trials BREEZE-AD1, BREEZE-AD2, and BREEZE-AD7, all of which were aimed at monotherapy and combination therapy. These studies were 16-weeks and phase 3, double-blind trials which looked at adult participants with moderate-to-severe AD and those with inadequate reactions to topical treatments for their conditions.

Those involved in BREEZE-AD1/2 had been given a once-per-day oral placebo or a 1 mg, 2 mg, or 4 mg of baricitinib. Those in BREEZE-AD7 were randomized by the study’s investigators for treatment with a once-per-day oral placebo, 2 mg, or 4 mg baricitinib in combination with topical corticosteroids (TCS).

The research team’s overall evaluation was centered on subjects’ EASI total scores, with the team looking at alterations in severity of AD based on lesion intensity as well as affected BSA. The team examined impacts of baricitinib therapy on individual EASI sign subscores, using a comparison between monotherapy and TCS combination therapy cohorts.

The results of the 1-mg arm of the BREEZE-AD1/2 studies were included, but the outcomes were reported for the doses known to be clinically-approved (2 mg and 4 mg).

The investigators also looked at demographics and baseline characteristic data, including subjects’ EASI subscores, and they were summarized using mean. Participants’ EASI subscore percent changes from the point of baseline (%CFB) were examined through the use of mixed model repeated measures (MMRM).

Subjects’ EASI subscores following the use of rescue therapy or following study drug cessation were excluded by the research team, with no adjustments for multiplicity being made. Those with a reported baseline score of 0 for a specific sign were also excluded from the team’s assessment of that sign.

Findings

The investigators found that the 4 mg dose of baricitinib led to rapid and sustained improvement with regard to all 4 of the clinical signs in both monotherapy and combination therapy arms of the analysis. Notably, the team also reported effects as early as week 1 for edema/papulation, excoriation, and erythema scores for both of the AD treatment approaches, adding that there was sustained significance through to 16 weeks.

Lichenification scores were also shown to have indicated early improvements, with the improvements becoming visible within the first week in the monotherapy cohort and the second week in combination therapy. Scores related to excoriation were found to have the highest effect magnitude, with subjects achieving near-maximal reduction in week 1 through the use of monotherapy and continuing to maintain the highest improvement throughout all of the timepoints in the combination therapy arm.

“These findings, along with the particularly early and profound reductions in excoriation marks, support the direct effects of baricitinib on reducing inflammation and alleviating itch in AD,” the investigators wrote. “This is in line with our understanding of the need for disrupting the itch–scratch cycle in order to successfully treat moderate-to-severe AD.”

References

1. ^{Wollenberg, A, Simon, D, Kulthanan, K, Figueras-Nart, I, Misery, L, Tangsirisap, N, et al. Baricitinib treatment rapidly improves the four signs of atopic dermatitis assessed by Eczema Area and Severity Index (EASI) clinical subscores. J Eur Acad Dermatol Venereol. 2023; 00: 1–8. https://doi.org/10.1111/jdv.19669.}
2. ^{Thyssen JP, Werfel T, Barbarot S, Hunter HJ, Pierce E, Sun L, et al. Maintained improvement in physician- and patient-reported outcomes with baricitinib in adults with moderate-to-severe atopic dermatitis who were treated for up to 104 weeks in a randomized trial. J Dermatol Treat. 2023; 34(1):2190430.}
3. ^{Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, et al. Efficacy and safety of baricitinib combined with topical corticosteroids for treatment of moderate to severe atopic dermatitis. JAMA Dermatol. 2020; 156: 1333–1343.}