Transitioning from Cyclosporine to Tralokinumab in Moderate-to-Severe Atopic Dermatitis: A Prospective Real-World Comparison of Direct Switch vs. Short Overlap

<b>Background</b>: Cyclosporine (CSA) is a fast-acting systemic immunosuppressant frequently used in moderate-to-severe atopic dermatitis (AD), but its long-term use is limited by toxicity. AD affects as many as 20% of children and nearly 10% of adults worldwide and its chronic, recurrent course often requires several systemic treatment lines, making optimization of sequential therapy a high clinical priority. Tralokinumab, an IL-13-targeting monoclonal antibody, represents a safer alternative with a slower onset of action. This study aimed to compare the effectiveness and safety of tralokinumab initiated as monotherapy versus in overlap with CSA during the transition from conventional to biologic therapy. <b>Methods</b>: We conducted a prospective observational study involving 27 adults with moderate-to-severe AD treated with tralokinumab for at least 16 weeks. Patients were categorized into two groups: tralokinumab monotherapy plus topical agents (TM; <i>n</i> = 23) and tralokinumab initiated with a cyclosporine overlap for up to 12 weeks (TO; <i>n</i> = 4). Disease severity was evaluated using the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and numerical rating scale (NRS) for pruritus at baseline and weeks 16, 24, and 52. <b>Results</b>: Both TM and TO groups demonstrated significant clinical improvement across all outcomes, with no statistically significant differences between groups (<i>p</i> > 0.05 for EASI, IGA, and NRS). At week 52, TM patients showed mean reductions of 18.66 (EASI), 2.21 (IGA), and 4.49 (NRS), while TO patients showed reductions of 15, 2, and 3.50, respectively. Tralokinumab was discontinued in eight patients (29.6%), most commonly due to lack of efficacy. Discontinuation rates did not differ significantly between groups. However, the very small size of the TO group (<i>n</i> = 4) substantially limits statistical power and any contrasts should be interpreted as exploratory. <b>Conclusions</b>: In this prospective real-world cohort, we observed improvement after initiating tralokinumab, with and without a short cyclosporine bridge. In light of CSA's risks, TM may be considered a reasonable first-line systemic option. Prospective randomized studies are needed to determine whether overlap confers additional benefit.