Drug survival of systemic and biological treatments for moderate‐to‐severe atopic dermatitis in adults: a multicentre retrospective observational study

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Dear Editor, Drug survival is a real‐life reflection of drug performance in routine medical practice and measures the patient’s persistence under a given treatment. Survival of systemic treatment of atopic dermatitis (AD) in routine clinical practice has been evaluated in previous analyses.1–3 Recently, dupilumab, a fully human monoclonal antibody that targets the interleukin‐4 receptor α, has been approved for the treatment of moderate‐to‐severe AD. Although its efficacy and effectiveness have been reported in previous clinical trials4 and real‐world evidence publications,5, 6 the drug survival analyses of dupilumab have, to date, been limited.7, 8 The aim of this observational retrospective study was to analyse drug survival and its associated variables in a cohort of patients with moderate‐to‐severe AD. A multicentre, retrospective observational study was conducted to assess the survival of systemic and biological treatments for moderate‐to‐severe AD in adults in real‐world clinical practice. This retrospective study was conducted in the dermatology units of eight reference hospitals from different regions of Spain, ensuring that the analysis was genuinely representative of the setting in which most patients with moderate‐to‐severe AD are managed. Data collected from medical records included patient demographics and baseline characteristics, concomitant diseases, familial record of atopic disease, severity measured by Investigator’s Global Assessment (IGA), adverse events (AEs) occurring throughout the follow‐up period, disease duration, number of previous systemic/biological treatments received, treatment dosage and reasons for withdrawal. Adult patients (aged ≥ 18 years) with moderate‐to‐severe AD (IGA 3/4) who received systemic or biological treatment for AD in any of the participating centres were included. The systemic treatments evaluated were ciclosporin (CsA), methotrexate (MTX), azathioprine (AZA), mycophenolate mofetil (MMF) and intravenous immunoglobulin (IVIg), and the biological treatment under study was dupilumab. This analysis retrospectively reviewed medical records of patients who initiated any of the drugs under evaluation in a period of 20 months (maximum possible length under treatment with dupilumab) prior to study closure in May 2019 and included all treatment courses of any of the drugs analysed during that period. As dupilumab was administered within a compassionate use programme, which required a baseline severity score of IGA 3/4, the systemic therapy sample included only those patients whose baseline severity was IGA 3/4. Baseline characteristics of all groups were similar (data not shown). A total of 240 patients received 420 courses of treatment during the study period. The mean ± SD number of treatments received was 2·59 ± 1·58. Specifically, 180 patients received CsA, 78 received MTX, 62 received AZA, 33 received MMF, 20 received IVIg and 47 received dupilumab. Overall, 58% of the total study group were men. The mean age was 36·4 ± 13·1 years. Regarding AD severity measured by IGA at baseline, 140 patients (66%) had an IGA score of 4, while the remaining 72 patients (34%) had an IGA score of 3. Kaplan–Meier analysis is shown in Figure 1. The median drug survival after 20 months was 36·67% for CsA, 32·05% for MTX, 27·41% for AZA, 36·36% for MMF, 30% for IVIg and 93·62% for dupilumab. Dupilumab showed a cumulative probability of drug survival that was significantly higher than any of the other therapies (log‐rank Mantel–Cox test, P < 0·001). A significant difference was also found between CsA and AZA (P = 0·02). Relative to each treatment, the most common causes of withdrawal were AEs (20% of the patients on treatment) for CsA, and primary failure (no response to the drug ever) for MTX, AZA, MMF, IVIg and dupilumab (32%, 38%, 38%, 25% and 4% of the patients on each treatment, respectively). No patients on MMF or dupilumab suspended treatment because of AEs. Kaplan–Meier survival analysis. This study provides a comparative survival analysis among most treatments available for moderate‐to‐severe AD. Regarding systemic drug survival, our findings are in reasonable agreement with previous studies. Likewise, reasons for discontinuation are also comparable with those found in the literature.1–3,7,8 Considering survival analysis as a reflection of the performance of a drug in daily practice, the results for dupilumab in our study demonstrate a clear superiority in terms of persistence compared with systemic therapy. The dropout rate for the dupilumab group was only 6% in 20 months, whereas it was above 65% for all the other drugs under study. A limitation of this study is the retrospective design, which is dependent on the quality of the medical records. The study population was sufficient to allow survival analysis, but broader cohorts may increase the power of the evidence. José Pereyra‐Rodríguez: Data curation (equal); Formal analysis (equal); Investigation (equal); Methodology (equal); Project administration (equal); Supervision (equal); Validation (equal); Visualization (equal); Writing‐original draft (equal); Writing‐review & editing (equal). Javier Jesus Dominguez‐Cruz: Data curation (equal); Formal analysis (equal); Investigation (equal); Methodology (equal); Project administration (equal); Supervision (equal); Validation (equal); Visualization (equal); Writing‐original draft (equal); Writing‐review & editing (equal). Ricardo Ruiz‐Villaverde: Data curation (equal); Formal analysis (equal); Investigation (equal); Methodology (equal); Project administration (equal); Supervision (equal); Validation (equal); Visualization (equal); Writing‐original draft (equal); Writing‐review & editing (equal). Juan Francisco Silvestre: Data curation (equal); Investigation (equal); Writing‐review & editing (equal). Manuel Galan: Data curation (equal); Investigation (equal); Methodology; Supervision (equal); Writing‐review & editing (equal). Laia Curto‐Barredo: Data curation (equal); Supervision (equal); Writing‐review & editing (equal). Ignasi Figueras Nart: Data curation (equal); Supervision (equal); Visualization (equal); Writing‐review & editing (equal). Esther Serra: Data curation (equal); Formal analysis; Investigation (equal); Methodology; Project administration; Supervision (equal); Writing‐original draft (equal); Writing‐review & editing (equal). José C. Armario‐Hita: Conceptualization (equal); Data curation; Formal analysis; Investigation (equal); Methodology; Project administration; Supervision; Validation; Visualization; Writing‐original draft (equal); Writing‐review & editing. Funding sources: none. Conflicts of interests: The authors declare they have no conflicts of interest.

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