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

Abstract Background Approved tralokinumab maintenance dosing regimens for treatment of moderate-to-severe atopic dermatitis (AD) include 300 mg every two weeks (Q2W) and every four weeks (Q4W), that clinicians may consider for patients who achieved clear or almost clear skin 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 (ie, 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) of the phase 3 ECZTRA 1 and 2 trials. Top-ranked factors were then assessed individually and together to identify factors associated with a similar maintained efficacy at Week 52 between patients re-randomized 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 tralokinumab Q4W patients 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%). Among patients with a stable achievement of both IGA 0/1 and worst daily pruritus NRS <3 from Weeks 12-16 with tralokinumab Q2W, similarly high maintained IGA 0/1 response at Week 52 were seen regardless of dosing regimen beyond Week 16 (Q2W: 72.0%; Q4W: 72.2%). 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 skin and no-to-mild itch over 4 consecutive weeks with tralokinumab Q2W.