Dupilumab-PEdiatric Skin Barrier Function and LIpidomics STudy in Patients With Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dupilumab-PEdiatric Skin Barrier Function and LIpidomics STudy in Patients With Atopic Dermatitis (NCT04718870), a non-randomized phase 4 study. The primary outcome is Percent Change From Baseline in Transepidermal Water Loss (TEWL) After 5 Skin Tape Stripping (STS) on Lesional Skin (LS) in AD Participants at Week 16.

2. Clinical Question

The study focused on skin barrier function, assessed through transepidermal water loss (TEWL) after skin tape stripping (STS). The primary outcome was specifically measured in lesional skin, meaning a predefined area affected by atopic dermatitis. Other stated objectives concerned TEWL measurements in lesional and non-lesional skin over time and comparison with normal skin in healthy volunteers.

The clinical question is therefore about change in a skin-function measurement during dupilumab treatment, rather than a randomized comparison of treatment against an untreated control. The healthy-volunteer group provides a reference context, but its members did not receive treatment and the primary outcome was not planned for that group.

3. Trial Design

This was a Phase 4, open-label, non-randomized, parallel-group study. It enrolled 41 participants and is recorded as completed. The study included pediatric participants with moderate to severe atopic dermatitis and healthy volunteers. The atopic dermatitis group received dupilumab; healthy volunteers received no treatment and were monitored in a similar way.

The healthy volunteers were matched to selected atopic dermatitis participants by age, gender, location of the targeted skin lesion area, and study site. Matching does not make the groups equivalent in all respects, and the study did not randomly allocate participants to treatment. As a result, the healthy-volunteer group is a reference group rather than a randomized control group suitable for an unqualified treatment-effect comparison.

The primary objective was to evaluate change in skin barrier function using TEWL after STS in predefined lesional skin among pediatric participants treated with dupilumab. The primary outcome was percent change from baseline to Week 16 in TEWL after 5 STS on lesional skin. Secondary objectives covered TEWL after STS in lesional and non-lesional skin, normal skin in healthy volunteers, and the time course of measurements during treatment and follow-up.

The registry lists a study start date of 2021-02-19 and a primary completion date of 2022-09-07. The full treatment schedule and detailed follow-up duration are not reported in the registry record. The record identifies the study as open-label, so masking was not used. Further details about how participants were recruited or selected are not reported in the registry record.

The trial design establishes the setting in which the outcome was measured, but it does not by itself provide evidence about the size or precision of change. The primary numerical outcome is not reported in the registry record. The registry lists 41 outcome measures and 0 analyses.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Healthy volunteer's cohort received no treatment and was considered as a reference comparator group.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was not planned to be collected and analyzed for Healthy Volunteer arm as pre-specified in protocol.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Analysis was performed on modified intent-to-treat (mITT) population which included all enrolled AD participants who received at least 1 dose of investigational medicinal product (IMP) and all enrolled healthy volunteers who had at least 1 TEWL/STS assessment performed, irrespective of compliance with protocol and procedures. If prohibited therapies used for AD, only visits prior to rescue treatment were considered.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline in Transepidermal Water Loss (TEWL) After 5 Skin Tape Stripping (STS) on Lesional Skin (LS) in AD Participants at Week 16, measured over Baseline, Week 16.

The primary endpoint is percent change from baseline in transepidermal water loss after 5 skin tape strips on predefined lesional skin at Week 16 among atopic dermatitis participants. TEWL is a noninvasive, in vivo measurement of water loss across the stratum corneum and is used to characterize skin barrier function. The registry describes TEWL combined with STS as a way to assess skin barrier function.

In STS, adhesive discs peel away uppermost layers of skin. TEWL was assessed before stripping and after 5, 10, 15, and 20 strips at specified time points. For the primary outcome, baseline and Week 16 assessments after 5 strips were conducted on the first of 3 closely adjacent, non-overlapping spots identified within predefined lesional areas. The outcome is a mean, with standard deviation specified as the measure of dispersion.

Percent change expresses the follow-up measurement relative to baseline on a percentage scale. As general statistical context, this can help describe relative change when the baseline level differs among participants, while the underlying measurement remains TEWL. A mean describes the average outcome in the analyzed group; a standard deviation describes the spread of individual measurements around that mean. Neither statistic alone establishes how precisely the mean is estimated.

The primary outcome is a skin-function measure, not a direct measure of symptoms or another clinical outcome. Its numerical estimate and uncertainty are not reported in the registry record, so the direction, magnitude, and precision of the observed change cannot be assessed from the registry information stated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary endpoint as a continuous measure summarized by a mean and standard deviation. It specifies percent change from baseline in TEWL after 5 STS on lesional skin at Week 16. The primary analysis population is described as mITT; for this outcome, the record defines the analyzed number as participants with available data. The outcome was not planned for the healthy-volunteer group.

What does a mean describe?

As general statistical background, a mean is an average that combines the measurements in an analyzed group into one summary value. It is useful for describing the central level of a continuous outcome, but it does not show how similar or different individual participants' measurements were. The standard deviation describes the spread of observations around the mean. A larger spread indicates more variation in the measurements, while a smaller spread indicates that they cluster more closely around the mean. Neither measure, by itself, quantifies uncertainty about the mean as an estimate of a wider population value.

What is percent change?

Percent change describes change in relation to a baseline measurement. As general statistical context, relative change can be informative when the scale of an outcome depends on its starting level. It should be interpreted alongside the outcome definition and, where available, the underlying measurements. The registry identifies the primary outcome as percent change in TEWL after 5 strips; it does not report the numerical change or the corresponding baseline and follow-up values.

Why measure TEWL after stripping?

The registry describes TEWL as a noninvasive, in vivo measurement of water loss across the stratum corneum, used to characterize skin barrier function. STS removes uppermost layers of skin using adhesive discs. Measuring TEWL before and after stripping combines a water-loss measurement with a standardized skin challenge. The primary endpoint uses the measurement after 5 strips, at baseline and Week 16, on a predefined lesional area. The record also describes assessments after 10, 15, and 20 strips, but these are not the primary endpoint specified.

What does precision mean?

As general statistical background, precision concerns how narrowly an estimate is determined by the data and analysis. A confidence interval is one way to communicate uncertainty around an estimate. Its width depends on factors including the variability of observations and the amount of usable information, as well as the analysis method. A narrow interval generally indicates greater precision than a wide interval, under the relevant assumptions. The registry record does not report a confidence interval for the primary outcome, or the estimate needed to interpret one.

Why does the design affect interpretation?

The study was open-label and non-randomized. The atopic dermatitis participants received dupilumab, whereas healthy volunteers received no treatment. As general statistical context, random assignment helps balance measured and unmeasured factors between treatment groups on average. Without random assignment, differences between groups may reflect factors other than treatment. Matching on age, gender, lesion-area location, and study site may help align selected characteristics, but it does not guarantee balance on all relevant factors. In addition, healthy volunteers are not an untreated atopic dermatitis comparison group.

The primary endpoint is a baseline-to-Week-16 outcome in treated atopic dermatitis participants. General interpretation of a within-group change should distinguish the observed change from a treatment effect: time, measurement conditions, and other influences may also contribute. The registry does not report an analysis that adjusts for such factors or a detailed statistical model, so those methods are not reported in the registry record.

What can be inferred from the reported analysis details?

The registry specifies the outcome's summary type and analysis population definition, but lists 0 analyses and does not report a numerical primary result. The registry record therefore does not provide enough information to assess the estimate, its uncertainty, or the specific inferential method used. A sample-size planning illustration, if present elsewhere, would be a planning calculation and not an observed measure of power; the registry does not report an original sample-size justification or its assumptions.

Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. For a continuous outcome summarized by a mean and standard deviation, the relevant model and its assumptions would need to be known before evaluating whether that concern applies. The registry record does not report a model, an over-dispersion assessment, or enough numerical results to evaluate model fit. These are general methodological considerations, not findings attributed to this study.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Atopic Dermatitis Participants")
n   <- c(18)
m   <- c(-38.5633)
sp  <- c(27.1211)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Atopic Dermatitis Participants  18  -38.563  27.121  -52.050  -25.076

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 41 outcome measures, including the primary endpoint and multiple secondary TEWL outcomes. These concern different skin areas, stripping levels, and groups, and include both percent and absolute change. When a study evaluates many outcomes, the chance of at least one apparently notable result can increase if each is tested separately. As general statistical context, multiplicity can be addressed through prespecified outcome hierarchies, adjusted testing procedures, or careful emphasis on estimation rather than isolated significance tests. The statistical plan for handling multiplicity is not reported in the registry record.

The record identifies the primary analysis population as mITT and defines the number analyzed for this outcome as participants with available data. It also states that the primary outcome was not planned for the healthy-volunteer group. This defines who was intended to contribute to the primary outcome, but it does not explain how missing measurements were handled or whether any imputation or sensitivity analyses were performed. Those methods are not reported in the registry record. The record does not provide the primary outcome's analyzed count or describe the extent or pattern of missing data.

Missing measurements can affect both the amount of information available and the representativeness of the analyzed participants. As general statistical context, an analysis limited to participants with available measurements may be biased if availability is related to outcome values or participant characteristics. Assessing that possibility requires information about missingness and the analysis approach, which is not reported in the registry record.

The registry lists 0 analyses, and no numerical primary result or inferential analysis is reported. Consequently, the handling of multiplicity, missing data, and any population deviations cannot be evaluated from the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events, other adverse events, and deaths separately for the two groups. Among healthy volunteers, 18 were at risk for serious adverse events and 0 were affected; 18 were at risk for other adverse events and 6 were affected; deaths were 0. Among atopic dermatitis participants, 23 were at risk for serious adverse events and 0 were affected; 23 were at risk for other adverse events and 21 were affected; deaths were 0.

These figures describe the registry's reported counts in each group. The record lists no serious adverse event terms, and it does not report details about the nature, severity, timing, or relatedness of the other adverse events. The counts alone do not establish whether an event was caused by treatment, and the untreated healthy-volunteer group is not a randomized safety comparator. Group differences in counts should therefore be read descriptively, not as an isolated estimate of treatment-related risk.

As general statistical context, safety counts depend on how events are defined, collected, and followed. The registry record does not report further detail about those procedures in the registry record stated for this study. The reported counts should not be interpreted as proof that an event could or could not occur.

13. What the Result Does, and Does Not, Mean

This study addresses a specific measurement question: change from baseline to Week 16 in TEWL after 5 skin tape strips on predefined lesional skin among pediatric participants with moderate to severe atopic dermatitis receiving dupilumab. The endpoint is a measure used to characterize skin barrier function. The trial record also describes other TEWL assessments across skin areas and stripping levels.

What the registry record does not establish is the numerical answer to the primary question. The primary estimate, its variability, and its uncertainty are not reported. The absence of a reported result is not evidence that the outcome did not change, nor is it evidence that it changed. The direction and magnitude remain unknown from the registry information.

The non-randomized, open-label design is another important boundary on interpretation. Participants with atopic dermatitis received treatment, while healthy volunteers were untreated and served as a matched reference group. This design can describe measurements in the studied groups, but it is not a randomized comparison of dupilumab against no treatment among participants with atopic dermatitis. Any observed change over time in the treated group could reflect treatment and other influences; the design alone cannot separate them.

The study is specific to pediatric participants with moderate to severe atopic dermatitis and to the TEWL measurement procedure described in the registry. The primary endpoint was not planned for the healthy-volunteer arm. The findings, if numerical results were available, would therefore need to be interpreted in the context of that population, the measurement method, and the stated Week 16 time point rather than treated as a general result for every patient group or outcome.

The registry identifies 41 outcome measures and 0 analyses. Without reported numerical results and details of the statistical analysis, statistical significance, precision, and the consistency of findings across outcomes cannot be assessed. The record supports a description of the research question and design, but not a conclusion about whether dupilumab changed skin barrier function.

14. Why This Trial Matters Statistically

Statistically, the study is notable for connecting a defined physiological measurement with a structured skin assessment. TEWL is used to characterize skin barrier function, and the protocol assessed it before and after STS. The primary endpoint focused on a specified stripping level, lesional skin, and a baseline-to-Week-16 comparison. Clear outcome definition is important because it distinguishes the primary question from the many related measurements in the registry.

The study also illustrates why a reference group and a causal control group are not interchangeable. Healthy volunteers were matched to selected atopic dermatitis participants on several characteristics and monitored similarly, but they were untreated and were not randomized with the atopic dermatitis group. That arrangement can provide context for normal skin measurements, while leaving the treatment effect difficult to isolate from other differences between the groups and changes over time.

The registry's outcome list contains multiple related endpoints, including measurements at different stripping levels and in lesional, non-lesional, and normal skin. This breadth can support exploration of how measurements vary across settings. It also makes prespecification and transparent reporting of multiplicity methods important. Those methods and the numerical analysis results are not reported in the registry record.

Finally, the record makes the distinction between an endpoint definition and an interpretable result especially clear. It identifies the mean and standard deviation as the primary summary approach and defines the outcome population in terms of available data, but lists 0 analyses. Without estimates and uncertainty, readers cannot judge precision or the pattern of change. The study's statistical importance lies in its focused measurement framework and in the limits that its design and incomplete results place on interpretation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary numerical result is not reported in the registry record, and the record lists 0 analyses. This prevents assessment of the observed change, its variability, its precision, and the statistical method used to obtain an inferential result. The registry identifies 41 outcome measures, but numerical results for the secondary outcomes are not reported in the registry record either.

The study was non-randomized and open-label. The healthy-volunteer group received no treatment, and the primary outcome was not planned for that group. Matching on age, gender, location of the targeted skin lesion area, and study site does not create a randomized untreated group of participants with atopic dermatitis. Consequently, the design cannot cleanly separate treatment-associated change from other sources of change or group differences.

The primary outcome is limited to percent change in TEWL after 5 STS on predefined lesional skin at Week 16. It is a skin barrier measurement, not a direct report of symptoms or another clinical outcome. The registry describes measurements at other stripping levels and in other skin areas, but those do not change the scope of the primary endpoint.

The primary analysis population is described as mITT, with participants counted as analyzed when data for the outcome were available. The registry does not report the analyzed count, missing-data methods, or sensitivity analyses. The full dosing schedule is not reported in the registry record; the arm description is incomplete. Detailed recruitment procedures, the statistical analysis plan, and the original sample-size justification are also not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dupilumab-PEdiatric Skin Barrier Function and LIpidomics STudy in Patients With Atopic Dermatitis — NCT04718870.
• Registry record last updated 2025-09-15; status last verified 2025-09.
• Results first posted 2023-10-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed Phase 4, open-label, non-randomized, parallel-group study of dupilumab in pediatric participants with moderate to severe atopic dermatitis, with an untreated healthy-volunteer reference group. Enrollment is listed as 41. The study start date is 2021-02-19, and the primary completion date is 2022-09-07.

The primary endpoint was percent change from baseline to Week 16 in TEWL after 5 STS on lesional skin among atopic dermatitis participants. TEWL was used to characterize skin barrier function. The primary outcome was specified as a mean with standard deviation, and the analysis population was described as mITT participants with available outcome data.

The registry lists 41 outcome measures and 0 analyses. The numerical primary result, missing-data methods, multiplicity procedures, and detailed statistical analysis plan are not reported in the registry record. The design and endpoint can be described, but the available record does not establish the direction, magnitude, or precision of the primary outcome.