Title : Relative efficacy of approved and investigational biologic monotherapies in atopic dermatitis
Abstract:
Atopic dermatitis (AD) is a chronic inflammatory skin disease marked by pruritus, eczematous lesions, and sleep disturbance, affecting adolescents and adults worldwide. Persistent itch disrupts sleep, contributes to psychological distress, impairs quality of life, and imposes substantial socioeconomic burden on patients and caregivers. Although topical therapies are effective for mild to moderate disease, many individuals with moderate-to-severe AD have inadequate control or recurrent flares and require systemic treatment. Before the advent of dupilumab, which targets T helper 2 (Th2) pathways, management of refractory AD relied on high-potency topical corticosteroids, systemic corticosteroids, and conventional immunosuppressants, approaches supported by limited evidence and constrained by unfavorable long?term safety profiles. Type 2 immune dysregulation driven primarily by IL?4, IL?13, and IL?31 is central to AD pathogenesis, contributing to skin?barrier dysfunction, inflammation, and pruritus.
Biologic therapies targeting maladaptive type 2 inflammation have transformed the management of moderate-to-severe AD; however, comparative evidence integrating both approved and next-generation investigational agents remains limited. This Bayesian network meta-analysis provides the first unified evaluation of all biologic monoclonal antibodies approved for AD monotherapy alongside emerging immunotherapies across key efficacy outcomes. A PRISMA-2020–compliant systematic review was conducted to identify phase 2 or phase 3 randomized, double-blind, placebo-controlled trials (RCTs) reporting week-16 outcomes (week-24 for rocatinlimab). A Bayesian random-effects network meta-analysis estimated relative risks (RRs) for EASI-75, EASI-90, IGA-AD 0/1, and ≥4-point improvement in itch Numeric Rating Scale, with treatment hierarchy assessed using SUCRA and P-scores. Seventeen randomized controlled trials including 6,366 patients were analyzed.
Across the evidence base of 17 RCTs, dupilumab (300 mg q2w), which blocks IL?4 and IL?13 signaling via IL?4Rα, remained the most consistently effective therapy, demonstrating predictable improvements in disease activity, skin clearance, and symptoms. It demonstrated the most consistent and precise efficacy across all endpoints, achieving RRs of 4.80 for EASI-75, 4.68 for EASI-90, 4.23 for IGA-AD 0/1, and 4.03 for clinically meaningful itch reduction. Rocatinlimab 300 mg q2w, an anti?OX40 antibody targeting activated CD4? and CD8? T cells, produced the strongest deep?response signals, with the highest absolute EASI?90, IGA 0/1, and itch?response rates. However, its wide BNMA credible intervals indicate uncertainty driven by small sample sizes and early?phase data. Rademikibart, temtokibart, and APG777 demonstrated favorable efficacy profiles, whereas telazorlimab showed variable or minimal benefit.
Overall, dupilumab remains the most reliable and effective biologic monotherapy for moderate-to-severe AD, while rocatinlimab and other emerging agents warrant further validation in larger phase-3 trials.
This comprehensive BNMA provides the first unified comparison of all approved biologics alongside next?generation investigational immunotherapies for moderate?to?severe AD. Together, these findings offer a comprehensive comparative framework to guide clinical decision?making and therapeutic sequencing for biologic monotherapy in AD, while underscoring the need for future head?to?head trials, longer?term safety evaluations, and mechanistic studies to define the optimal placement of next?generation immunotherapies within the evolving treatment landscape.
