Predicting success with reduced dosing frequency of tralokinumab in patients with moderate-to-severe atopic dermatitis.

Background: Approved tralokinumab maintenance dosing regimens for treatment of moderate-to-severe atopic dermatitis (AD) include 300 mg every 2 weeks (Q2W) and every 4 weeks (Q4W). Clinicians may consider tralokinumab Q4W for patients whose skin has become clear or almost clear at week 16 with initial Q2W dosing.

Objectives: To identify predictive factors associated with maintained response after switching to tralokinumab Q4W, evaluate recapture of treatment response after relapse on Q4W, and assess treatment-emergent immunogenicity with tralokinumab Q4W.

Methods: These post hoc analyses utilized machine learning to identify predictive factors for maintained treatment response at week 52 using data from the week 16 responder population of the phase III ECZTRA 1 and 2 trials, i.e. patients who met Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab Q2W monotherapy. Top-ranked factors were then assessed individually and together to identify factors associated with a similar maintained efficacy at week 52 between patients rerandomized to tralokinumab Q2W or Q4W monotherapy at week 16. Additionally, the probability of recapturing IGA 0/1 and/or EASI 75 response after relapse was assessed in patients on tralokinumab Q4W transferred to the open-label arm.

Results: The two top-ranked predictive factors for maintained response at week 52 were IGA score at week 16 (76.1%) and worst daily pruritus numeric rating scale (NRS) < 3 at week 16 (56.5%). Patients whose AD reached stable clinical response scores of both IGA 0/1 and worst daily pruritus NRS < 3 from weeks 12-16 with tralokinumab Q2W similarly maintained IGA 0/1 response at week 52 regardless of dosing regimen beyond week 16 (72.0% of patients on Q2W and 72.2% of those on Q4W). Of patients who relapsed on Q4W, 94.6% recaptured treatment response after returning to Q2W dosing. The immunogenicity potential of tralokinumab was low, and patients with positive antidrug antibodies did not show loss of efficacy or higher incidences of adverse events.

Conclusions: These data suggest that Q4W is an effective dosing regimen for most patients who achieved stable disease control as shown by clear/almost clear skin and no itch to mild itch over 4 consecutive weeks on the initial regimen of tralokinumab Q2W.