Stable Clear-Almost Clear Response is Sustained up to 3 Years in Patients with Moderate-To-Severe Atopic Dermatitis Treated With Lebrikizumab

Abstract

Background Lebrikizumab, a monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, is indicated for the treatment of adults and adolescents (≥12 years of age who weigh ≥40 kg) with moderate-to-severe atopic dermatitis (AD), whose AD is either inadequately controlled with or not suitable for topical therapies. Prior analyses from phase 3 trials (ADvocate1, NCT04146363; ADvocate2, NCT04178967; ADjoin NCT04392154) in patients showed the achievement and maintenance of deep skin response, defined by total skin clearance, through 3 years of lebrikizumab treatment. In this post hoc analysis, we assessed individual patient stability of deep skin clearance response up to 3 years in Week-16 responders who continued the same treatment (lebrikizumab every 4 weeks [Q4W] or every two weeks [Q2W]).

Methods We assessed the subpopulation of patients who responded at Week 16 to 250-mg lebrikizumab Q2W with ≥90% or 100% reduction in Eczema Area and Severity Index (EASI 90 or EASI 100), who completed ADvocate1 and ADvocate2 (1-year), and who enrolled in the long-term extension study, ADjoin, and received either lebrikizumab Q4W or Q2W for an additional 2 years. Although topical corticosteroids were allowed in the ADvocate1 and ADvocate2 maintenance period (Week 16-52) and in ADjoin, its overall use was low. Pruritus daily diary data were collected through Week 104 and not included in this analysis. We analyzed the proportion of patients who maintained a stable response, defined as achieving EASI 90 or EASI 100 in at least 80% of visits, from Week 16 to 152. We report observed data.

Results At Week 16, 64% (63/99) of patients receiving lebrikizumab Q4W achieved EASI 90 and 19% (19/99) achieved EASI 100, and 65% (53/82) of patients receiving lebrikizumab Q2W achieved EASI 90 and 27% (22/82) achieved EASI 100. From Week 16 to 152, the proportion of EASI 90 responders who maintained stable EASI 90 was 78% (49/63) with lebrikizumab Q4W and 81% (43/53) with lebrikizumab Q2W. The proportion of EASI 100 responders who maintained stable EASI 100 was 58% (11/19) with lebrikizumab Q4W and 64% (14/22) with lebrikizumab Q2W.

Conclusions The majority of lebrikizumab Week-16 responders sustained a stable clear or almost-clear skin response with no or minimal fluctuations, with up to 3 years of continuous treatment with lebrikizumab.  This maintenance of response over time provided by lebrikizumab is clinically significant in the context of a chronic and relapsing disease, where long-term disease control remains one of the most critical unmet needs.