Adult patients with moderate-to-severe atopic dermatitis (AD) in the phase 3 BREEZE-AD7 study showed sustained improvement of AD signs and symptoms after 68 weeks with combination treatment of bariticitinib and topical corticosteroids.
Combination therapy of baricitinib and topical corticosteroids (TCS) showed clinically meaningful sustained efficacy in the treatment of adult patients with moderate to severe atopic dermatitis (AD) over 68 weeks, according to study findings published in the Journal of the European Academy of Dermatology and Venereology.
Combination therapy is the current standard of care in AD management, in which the addition of systemic therapy and/or phototherapy is recommended along with TCS for effective control of AD in patients with inadequate response to topical therapies.
“Due to limited efficacy and adverse risks associated with systemic therapies, there is an apparent need for alternative therapeutic options to curb the inflammatory effects of AD,” wrote the study authors.
Baricitinib, an oral selective Janus kinase (JAK) 1/JAK2 inhibitor, has previously demonstrated significant improvement of clinical signs and symptoms of AD following 16 weeks of treatment as a monotherapy (BREEZE-AD1 and BREEZE-AD2) and when combined with TCS (BREEZE-AD7).
Seeking to examine long-term efficacy of baricitinib combined with TCS in adult patients, researchers recruited participants who completed 16 weeks of treatment in the combination therapy study to take part in a 52-week extension analysis (week 68 of continuous therapy), BREEZE-AD3 (NCT03334435).
Upon BREEZE-AD7 completion, patients were classified as (1) responders, defined as those who scored 0 (clear) or 1 (almost clear) for the Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) and did not receive rescue therapy during the originating study; (2) partial responders with vIGA-AD score of 2 (mild) and never rescued during the originating study; and (3) nonresponders (NR) with vIGA-AD score of 3 (moderate) or 4 (severe), or rescued during the originating study.
Responders or partial responders receiving baricitinib 2-mg or 4-mg plus TCS maintained their original treatment doses in BREEZE-AD3. Nonresponders receiving baricitinib 2 mg were rerandomized 1:1 to baricitinib 2 mg or 4 mg, and nonresponders receiving baricitinib 4 mg remained on the same dose.
Integrated data from all patients (responders, partial responders, and nonresponders, baricitinib 4-mg intent-to-treat [ITT] cohort; n = 102) receiving continuous baricitinib 4 mg in BREEZE-AD7 through BREEZE-AD3 were analyzed, along with baricitinib 4 mg (n = 63) or 2 mg (n = 53) responder and partial responder cohorts.
The primary end point assessed was the proportion of patients with a vIGA-AD score of 0 or 1 at week 16, 36, and 52 (week 32, 52, and 68 of continuous therapy). Secondary efficacy end points included the proportion of patients achieving 75% improvement from baseline in the Eczema Area and Severity Index score (EASI75) and Itch Numeric Rating Scale (NRS) improvement of 4 or more points from baseline (up to week 32).
Findings examining the baricitinib 4-mg ITT cohort showed that the proportions of patients achieving vIGA-AD (0,1) at week 32, week 52, and week 68 were 21.6%, 26.5%, and 23.5%, respectively, and those achieving EASI75 were 46.1%, 40.2%, and 43.1%, respectively. Four-point or more improvements in Itch NRS were observed among 47.3% patients at week 16 and 40.6% at week 32.
For the baricitinib 4-mg responder/partial responder cohort, proportions of patients achieving vIGA-AD (0,1) at week 32, week 52, and week 68 were 31.7%, 33.3%, and 34.9%, respectively, and EASI75 were 57.1%, 49.2%, and 49.2%, respectively. Improvement in Itch NRS by 4 points or more was observed among 53.6% of participants at week 16 and 46.4% at week 32.
Furthermore, corresponding proportions for baricitinib 2-mg responder/partial responder cohort for vIGA-AD (0,1) at week 32, week 52, and week 68 were 39.6%, 45.3% and 30.2%, respectively, and EASI75 were 77.4%, 69.8% and 58.5%, respectively. Improvements in Itch NRS by 4 points or more were shown in 56.3% of patients at week 16 and 47.9% at week 32.
Researchers noted several limitations of the study, including the relatively small patient numbers compared with the monotherapy studies, no patient-reported outcomes collected beyond week 32 of continuous therapy, and no long-term data assessment for the placebo group due to a decrease in sample size.
They concluded that findings provide support that baricitinib may be a longer-term treatment option for moderate to severe AD.
Silverberg JI, Simpson EL, Thyssen JP, et al. Long-Term efficacy (up to 68 weeks) of baricitinib in combination with topical corticosteroids in adult patients with moderate-to-severe atopic dermatitis: analysis of treatment responders, partial responders and nonresponders originating from study BREEZE-AD7. J Eur Acad Dermatol Venereol. Published online December 14, 2022. doi:10.1111/jdv.18816