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 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.; Atopic dermatitis (AD) is a chronic, itchy skin disease. Patients whose AD can’t be controlled with topical (applied to the skin) prescription treatments often need long-term oral or injectable treatments. Tralokinumab is a biologic medication (derived from living organisms) that is injected under the skin. It is approved for treating AD at two different dosages: a standard initial dose of 300 mg every 2 weeks (Q2W) and a reduced dosing frequency option, every 4 weeks (Q4W) for patients who have achieved clear or almost clear skin with Q2W dosing. In our study, we analysed factors associated with maintaining clear/almost clear skin after switching from tralokinumab Q2W to Q4W, using data from two clinical trials (ECZTRA 1 and 2) funded by LEO Pharma A/S. In these trials, patients initially received tralokinumab Q2W for 16 weeks. Those who responded well either continued with Q2W dosing for another 36 weeks or switched to less frequent Q4W dosing. The top factors associated with maintenance of clear/almost clear skin were achievement of both clear/almost clear skin and experiencing no-to-mild itch symptoms at week 16. Among patients who experienced stable disease control with Q2W dosing (clear/almost clear skin and no-to-mild itch over a 4-week period), a similarly high percentage maintained clear/almost clear skin after switching to Q4W dosing as those who continued on Q2W dosing. Importantly, patients who worsened after switching to Q4W were able to regain disease control by returning to Q2W dosing. Our findings can help identify patients who are most likely to successfully switch from tralokinumab Q2W to Q4W.