Maintenance management after dupilumab discontinuation in moderate-to-severe atopic dermatitis: a comparative study of proactive intermittent tacrolimus and reactive rescue therapy

Moderate-to-severe atopic dermatitis (AD) often relapses after dupilumab discontinuation. This study compared proactive intermittent tacrolimus versus on-demand therapy for post-discontinuation maintenance. This was a real-world, mixed retrospective–prospective observational study conducted at a single dermatology center. Patients who discontinued dupilumab were identified through retrospective chart review, and a subset was followed prospectively. Based on observed post-discontinuation topical management patterns, patients were classified into a proactive maintenance group or a reactive, as-needed treatment group. Patients were followed for 24 weeks, with extended follow-up to 52 weeks for exploratory analyses. The primary outcome was time to first flare. Median follow-up was 28 weeks. Proactive maintenance prolonged flare-free survival (HR 0.62, 95% CI 0.45–0.86, p = 0.004), reduced flare rate (IRR 0.68, 95% CI 0.52–0.88, p = 0.003), and lowered steroid use (mean difference −18.4 g, p < 0.001). PROs improved more (POEM β −2.1; DLQI β −1.8). Local reactions were comparable (8.3 vs. 7.9%); no serious adverse events occurred. Proactive intermittent tacrolimus after dupilumab reduces flare risk and steroid burden, improving outcomes, and is a feasible maintenance strategy.