Atopic dermatitis (AD) is a chronic, relapsing disease that can start at any age and has a significant negative impact on quality of life [1]. Patients with moderate-to-severe disease experience a substantial burden dominated by pruritus, which can profoundly impact sleep, daily functioning and quality of life [1, 2].

Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)−4 and IL-13, and thus inhibits the signaling of both cytokines. These cytokines are thought to be key drivers of the type 2 inflammation that characterizes AD and a number of other diseases that are often comorbid with AD, such as asthma, allergic rhinitis and food allergies [3]. Clinical trials of dupilumab in AD have demonstrated significant improvements in signs and symptoms of AD, including pruritus and quality of life [4, 5], with good efficacy and acceptable safety results reported for up to 5 years of dupilumab treatment in a clinical trial extension study and two real-world studies [6,7,8]. A retrospective analysis of 356 patients treated with dupilumab found a correlation between improvements in Peak Pruritus Numeric Rating Scale (PP-NRS) scores and both Dermatology Life Quality Index (DLQI) and Patient-Oriented Eczema Measure scores [9]. In addition, the authors of a pooled analysis of two phase 3 trials also reported improvements in quality of life measures in parallel with PP-NRS improvements following 2 weeks of treatment, which were maintained through week 16 [5].

PROSE is an ongoing, prospective, observational, multicenter registry in the USA and Canada, designed to collect real-world data from patients aged ≥ 12 years with moderate-to-severe AD who initiate dupilumab in accordance with country-specific prescribing information (ClinicalTrials.gov identifier: NCT03428646). A previous interim analysis of PROSE registry data over a 2-year period revealed substantial and sustained improvements in AD signs [as measured by the Eczema Area and Severity Score (EASI), symptoms (including PP-NRS), quality of life (DLQI) and a one-item clinician-assessed global severity question, the Overall Disease Severity (ODS) score] [10].

As an observational registry study, no specific protocol response definitions were mandated in PROSE. The ODS score asks the clinician to rate the answer on a 0 to 4 scale to the question, “Taking into account all important aspects characterizing the severity of AD, how would you grade your patient’s AD at this time?”. A related measure of clinician-assessed global AD severity, the Investigator’s Global Assessment (IGA), which only addresses the severity of certain lesional signs, is universally utilized in clinical trials of advanced systemic AD treatments; it is often also rated on a 0 to 4 scale.

For itch, the percentage of patients in a treatment group experiencing at least a 4-point reduction in PP-NRS is a typical response definition in clinical trials of advanced systemic AD treatments, including those for dupilumab [11, 12]. Recently, achievement of a PP-NRS score of 0/1 has started to be used as an endpoint in randomized clinical studies assessing new treatments for moderate-to-severe AD, and has been described as a stringent, high-threshold endpoint [13,14,15,16]. While this endpoint is considered to be stringent by some, no analysis has shown whether a response definition based on PP-NRS scores of 0 or 1 is clinically distinguishable from any other cutoff point. Nevertheless, the availability of data reporting this endpoint in patients treated with some advanced therapies may allow for indirect comparisons, with the caveat that a different study design and population differences must also be considered.

The present interim analysis of the PROSE study was conducted to report the proportion of patients achieving PP-NRS scores of 0/1 over time, and also the achievement of no/minimal disease (a score of 0 or 1) on the clinician-assessed ODS, in patients older than 12 years with moderate-to-severe AD, 3 years after starting dupilumab treatment.