Down-Titration of Baricitinib Maintains Efficacy in Atopic Dermatitis

Flexible baricitinib dosing is feasible for the treatment of moderate to severe atopic dermatitis (AD), according to study findings published in Journal of Dermatological Treatment.

This study was a substudy of the BREEZE-AD3 (NCT03334435) randomized clinical trial. Participants who were enrolled in BREEZE-AD1 (NCT03334396), BREEZE-AD2 (NCT03334422), and BREEZE-AD7 (NCT03733301) trials were eligible for BREEZE-AD3. Participants (N=168) who responded or were partial responders to baricitinib 4 mg daily at week 52 were randomly assigned again in a 1:1 ratio to continue baricitinib 4 mg (n=84) or down-titrate to baricitinib 2 mg (n=84) through week 104. The outcomes of interest in this substudy were a validated Investigator Global Assessment (vIGA) score of  0 or 1, 75% improvement in Eczema Area and Severity Index (EASI) score (EASI75), and patient-reported outcomes. Relapse was defined as a vIGA score over 3.

The continue and down-titrate cohorts comprised 36.9% and 35.7% women, of whom were a mean age of 38.1 (SD, 14.3) and 38.8 (SD, 15.3) years, and had a BMI of 25.8 (SD, 4.9) and 25.7 (SD, 5.4) kg/m², respectively. They had a mean AD duration of 26.9 (SD, 16.0) and 24.9 (SD, 16.7) years, 61.9% and 72.6% were White, EASI scores at baseline were 4.2 (SD, 3.9) and 4.4 (SD, 5.1) points, and body surface area (BSA) affected was 8.7% and 8.7%, respectively.

Fewer participants who down-titrated baricitinib discontinued treatment (17.9%) compared with those who maintained their dose (26.2%). However, more participants in the down-titration group discontinued due to lack of efficacy compared with those in the continue group (10.7% vs 8.3%), respectively.

Among patients who relapsed between weeks 52 and 104 after down-titration (n=41), most (85.4%) re-achieved vIGA and EASI75 (58.5%) outcomes.

Responses to treatment and patient-reported outcomes were generally maintained among the cohort who remained on baricitinib 4 mg.

Among those in the down-titration group, the rate of vIGA response at week 52 (51.2%) decreased at weeks 68 (45.2%) and 104 (35.7%) whereas the EASI75 outcome was better maintained from week 52 (84.5%) to weeks 68 (58.3%) and 104 (58.3%).

For patient-reported outcomes, a Dermatology Life Quality Index score of 0 or 1, indicating no impact to patient’s life, was reported by 34% at week 52 and maintained at week 68 (34.5%) and 104 (34.5%). Other patient-reported outcomes changed little during BREEZE-AD3 among those in the down-titration cohort. With the exception that SCORing Atopic Dermatitis (SCORAD) itch scores numerically decreased when compared with baseline, from a least-squares mean difference of -4.3 points at week 52 to -3.0 points at week 104.

The major limitation of this analysis was the lack of diversity among the participants.

Study authors conclude, “Patients who continued on baricitinib 4 mg from week 52 to 104 maintained greater control in some outcome measures relative to patients who were re-randomized to baricitinib 2 mg, with somewhat greater maintenance of EASI75 and SCORAD itch. Improvement in patient-rated outcomes was sustained in both treatment arms.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.