We read with great interest the article by M. Gooderham and colleagues discussing the efficacy of tralokinumab for up to 4 years in adults with moderate-to-severe atopic dermatitis (AD).1 The authors provide one of the longest follow-ups to date for a biological therapy in AD, showing sustained improvements in both clinician- and patient-reported outcomes. In this post hoc analysis of patients who completed 1 year of tralokinumab in the parent ECZTRA trials and up to three additional years in the ECZTEND extension, 84.5% experienced an improvement of at least 75% of the Eczema Area and Severity Index (EASI-75), and more than half reached Investigator's Global Assessment (IGA) 0/1 at week 152.1, 2 Importantly, a large proportion of patients met treat-to-target thresholds, including EASI ≤ 7, pruritus Numeric Rating Scale (NRS) ≤ 4 and Dermatology Life Quality Index (DLQI) ≤ 5, indicating low-residual disease burden across multiple domains.1, 3 Beyond response rates at single time points, the most clinically relevant aspect of this analysis may be the stability of disease control over time. AD is a chronic condition with frequent flares, and cross-sectional outcomes may fail to reflect the real patient experience. In this context, the authors' evaluation of response stability provides valuable insights: more than 70% of patients maintained EASI ≤ 7 for at least 80% of days over 3 years of extension treatment.1 Such findings suggest a shift from intermittent disease suppression towards sustained control. This concept is closely linked to the emerging hypothesis of disease modification in AD.4 In the present study, a substantial proportion of patients achieved and maintained optimal clinical responses, with some individuals sustaining very low-disease activity over long periods.1 In addition, previous analyses of lesional skin biopsies from tralokinumab-treated patients have shown a progressive normalization of inflammatory and barrier-related gene expression profiles towards those observed in non-lesional skin.1 Together, these findings raise the possibility that long-term IL-13 inhibition may also interfere with the underlying pathogenic processes that drive chronic inflammation. While the concept of disease modification is well established in other chronic inflammatory conditions, its definition in AD is still debated.4 Long-term stability, reduced need for rescue therapy and sustained improvements in quality of life may represent pragmatic markers of disease modification, but standardized criteria are still lacking. This study contributes to this evolving discussion by showing that deep and stable responses can be maintained for several years in a relevant proportion of patients. Nevertheless, the results should be interpreted in the context of the study design. The analysis included only patients who completed the parent trials and entered the open-label extension, with a potential selection bias towards individuals with better responses. As acknowledged by the authors, such populations may not fully represent the broader spectrum of patients treated in clinical practice.1 In parallel, real-world evidence is progressively complementing long-term trial data. Observational studies with targeted therapies have shown that sustained responses, improvements in patient-reported outcomes and treatment persistence can be achieved outside the strict selection criteria of trials.5 The integration of long-term clinical trial results with real-world evidence will be crucial to better identify predictors of better clinical responses and to assess if those may translate into true disease modification. Overall, this study provides reassuring long-term data on the efficacy and safety of tralokinumab and highlights the importance of sustained disease control as a meaningful therapeutic goal. At the same time, it adds to the growing body of evidence suggesting that targeted therapies may influence the long-term trajectory of atopic dermatitis. Future studies, particularly in real-world settings and in early disease stages, will be essential to clarify whether sustained deep responses can translate into true disease modification. The authors have nothing to report. L. Gargiulo has been a consultant and/or speaker and has participated in advisory boards for AbbVie, Amgen, Almirall, Novartis, Johnson and Johnson, Eli Lilly, Sanofi, Pierre Fabre, BMS, LEO Pharma, UCB and Pfizer. A. Narcisi has served on advisory boards, received honoraria for lectures and research grants from Almirall, AbbVie, Leo Pharma, Celgene, Eli Lilly, Janssen, Novartis, Sanofi-Genzyme, Amgen and Boehringer Ingelheim. Not applicable. Not applicable. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Gargiulo et al. (Sat,) studied this question.