EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients (NCT04998604), a randomized phase 4 study. The primary outcome is Change From Baseline to Week 24 in Nasal Polyp Score.

2. Clinical Question

The study, titled “EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients,” is a Phase 4, randomized, parallel-group, triple-masked head-to-head trial. Its primary objective was to evaluate dupilumab compared with omalizumab for reducing polyp size and improving sense of smell. The posted primary outcome concerns polyp score; smell and other symptoms appear among the secondary outcomes.

The main statistical question is comparative rather than whether either group's score changed in isolation: the estimate contrasts the groups' baseline-to-Week 24 changes. The registry reports a least-squares mean difference and its confidence interval from an ANCOVA analysis. The clinical importance threshold for this score is not reported in the registry record, so the numerical difference alone does not establish how important the change is to patients.

3. Trial Design

NCT04998604 is a completed, randomized, parallel-group Phase 4 trial. Its official title describes a double-blind, head-to-head comparison in severe CRSwNP with comorbid asthma; the registry also records triple masking. The listed enrollment is 360. The registry gives a start date of 2021-09-27 and a primary completion date of 2024-10-16.

The two treatment groups described for the primary comparison received dupilumab 300 mg subcutaneously every 2 weeks or omalizumab 75 to 600 mg subcutaneously every 2 or every 4 weeks, each for 24 weeks. Omalizumab dosing was based on serum IgE levels and body weight. Although placebo appears in the registry's intervention list, the arm descriptions and posted primary comparison concern dupilumab and omalizumab; a placebo arm is not described in the posted primary results.

The primary outcome was change from baseline to Week 24 in nasal polyp score (NPS). The registry describes an ITT analysis set containing all randomized participants, but states that only those with Week 24 data are reported for this outcome. The arm-level outcome summaries give n=172.0 for dupilumab and n=165.0 for omalizumab. These are the reported primary-outcome analysis counts, not a restatement of the enrollment figure.

Secondary outcomes cover nasal symptom diary scores, including loss of smell, nasal congestion and total symptom score; SNOT-22 total and nasal-domain scores; nasal peak inspiratory flow; rhinosinusitis visual analogue scale; and treatment-emergent adverse events, serious adverse events and adverse events of special interest. The study status is completed. Further operational details, including a fuller account of masking procedures or any changes to the protocol, are not reported in the registry record.

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: A total of 360 participants were randomized in a 1:1 ratio to receive either dupilumab or omalizumab in the study. Randomization was stratified by prior surgery for nasal polyp, inhaled corticosteroids (ICS) doses (low versus medium/high dose ICS), presence of aspirin-exacerbated respiratory disease (AERD) and region \[Eastern European (EE) versus Rest of the World (ROW)\].

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The ITT analysis set included all randomized participants. Only participants with data collected at Week 24 are reported.

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: The intent-to-treat (ITT) analysis set included all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to Week 24 in Nasal Polyp Score, measured over Baseline (Day 1) and Week 24.

The primary endpoint is change from baseline to Week 24 in nasal polyp score. An independent physician assessed polyp extent and severity using nasal endoscopy. Each nostril was scored from 0, meaning no polyps, to 4, meaning large polyps causing complete obstruction of the inferior nasal cavity. The two nostril scores were added to produce a total from 0 to 8, with higher scores representing more extensive or severe polyps.

The endpoint is a continuous measure: it can represent different degrees of severity rather than only whether a participant did or did not meet a threshold. Change from baseline makes the comparison about movement in score over the treatment period. Negative change means less polyp severity than at baseline. The registry defines baseline as the last available valid, non-missing value up to and including the day of first study treatment administration.

For each group, the posted summary is a least-squares mean change with a 95% confidence interval. The primary comparison is the least-squares mean difference between groups. In general, an endoscopic score can provide a structured assessment of polyp burden, while symptom and quality-of-life measures capture other aspects of the condition. This trial also listed sense-of-smell outcomes among its secondary measures. The registry record does not report a threshold for a clinically important change in NPS, so the score's numerical scale should not be mistaken for a direct measure of patient-perceived benefit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a change score represent?

In general, a change score is the follow-up measurement minus the baseline measurement. Here, the registry defines negative change as less severe nasal polyps. The group estimates therefore describe average movement on the NPS scale, not the number of participants whose polyps improved and not the proportion who reached a particular response threshold. No responder threshold is reported in the registry record.

The NPS is a continuous outcome. In general, continuous outcomes retain information about the magnitude of a measurement, while binary outcomes divide observations into categories. A continuous analysis can estimate an average difference, but that average does not show how outcomes are distributed among individuals. The registry does not report participant-level distributions for this outcome.

What does ANCOVA do?

In general, analysis of covariance (ANCOVA) models an outcome while accounting for one or more other variables. In a trial with a baseline and follow-up measurement, ANCOVA can be used to compare groups while adjusting for baseline outcome values and any other prespecified covariates. Such adjustment may improve precision when the chosen variables predict the outcome. The specific covariates and model specification for this trial are not reported in the registry record, so it is not possible to say which variables were included or how they were handled.

The registry reports least-squares means and a least-squares mean difference. In general, a least-squares mean is a model-based group estimate, interpreted at a common setting of the model's covariates. It is therefore not necessarily identical to the raw arithmetic mean. The between-group estimate is the model's contrast between the two treatment groups, rather than a new calculation from the displayed group estimates.

How should the confidence interval be read?

In general, a confidence interval expresses uncertainty around an estimated quantity under a statistical model and its assumptions. The 95% confidence interval for the reported difference is -1.96 to -1.25. Its position below zero is consistent with a negative between-group contrast under the stated direction of subtraction. The width reflects uncertainty in the estimate; it is not an interval containing 95% of individual participant outcomes, nor does it capture every possible source of bias or uncertainty.

Each group estimate also has a 95% confidence interval: -2.95 to -2.36 for dupilumab and -1.35 to -0.75 for omalizumab. Comparing overlap between separate group intervals is not a substitute for the trial's direct model-based comparison. The registry reports that direct comparison through the ANCOVA least-squares mean difference and its own interval.

What does the p-value say?

In general, a p-value measures how incompatible the observed data, or more extreme data, are with a specified null hypothesis if that hypothesis and the analysis assumptions hold. The reported p-value is p < 0.001. This indicates strong statistical evidence against the null hypothesis for the reported comparison, but it does not measure the size or clinical importance of the effect. It does not mean that there is a particular probability that one treatment is better, and it does not account automatically for testing multiple outcomes.

The registry classifies the analysis as a superiority comparison. The reported estimate, interval and p-value are the evidence attached to that primary comparison. A superiority label does not establish that every secondary outcome favors the same group, nor does it convey a clinical-importance threshold that is not reported.

What can the arm counts tell us?

The primary summaries report n=172.0 for dupilumab and n=165.0 for omalizumab. The registry states that the ITT analysis set included all randomized participants, but only participants with Week 24 data are reported for this endpoint. Thus, the analysis-set description and the reported outcome counts answer different questions: one describes who was assigned to the intended analysis set, while the other describes whose endpoint data are represented in the posted result. The registry record does not explain the reasons for unavailable Week 24 measurements or the method used to handle missing outcomes.

In general, missing outcome data can affect both precision and the validity of an estimate, particularly if missingness is related to outcome or treatment. Different methods rely on different assumptions. Without details of the missing-data procedure and sensitivity analyses, the robustness of the estimate to missing observations cannot be assessed from the registry record.

How do planning illustrations differ from power?

In general, a sample-size planning illustration uses assumptions about an effect and a statistical design to show what a future study might require. The planning description for this trial uses the observed effect, a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of the observed effect. These are planning assumptions, not evidence about the trial's achieved power. A post hoc calculation based on the observed result is not observed power and cannot replace the confidence interval as a description of estimate precision.

The sample-size justification used when this trial was designed is not reported in the registry record. Nor are the protocol's target effect, design assumptions, or any interim-analysis plan reported. The planning illustration should therefore be kept distinct from the trial's actual enrollment and the analysis counts attached to the endpoint.

Finally, multiplicity matters when a study assesses several outcomes or performs several statistical tests. In general, repeated testing can raise the chance of at least one apparently significant result unless the analysis plan addresses that issue. The registry lists a primary endpoint and multiple secondary outcomes, but multiplicity procedures, any testing hierarchy, and any adjustment of p-values or confidence intervals are not reported in the registry record. The primary p-value should be interpreted as the result of the stated comparison, without assuming an unreported multiplicity adjustment.

10. Analyses Reported by the Sponsor

The registry reports an ANCOVA comparison of least-squares means: the difference is -1.60, with a 95% confidence interval from -1.96 to -1.25 and p < 0.001. This is the reported model-based comparison and should be distinguished from a simple, unadjusted calculation based on group summaries. A separate unadjusted recalculated comparison is not reported in the registry record, so there is no additional recalculated estimate to set beside the ANCOVA result.

The group-level least-squares mean changes are -2.65 for dupilumab and -1.05 for omalizumab. Their contrast is not a substitute for the reported ANCOVA estimate, because the ANCOVA may account for model terms not visible in the group summaries. The covariates and model details are not reported in the registry record. No discrepancy is flagged between the posted analysis and any recalculation, but the primary inferential result remains the registry's reported ANCOVA analysis.

In general, an unadjusted recalculation can serve as a check on a published comparison when the necessary summary information is available, but it may differ from an adjusted model. The analysis model, its assumptions and the reported uncertainty should guide interpretation. The registry record does not report enough detail to reconstruct the ANCOVA independently.

11. Multiplicity, Missing Data and Analysis Populations

The primary outcome is change in NPS from baseline to Week 24. The registry also lists secondary measures of loss of smell, nasal congestion, total symptom score, SNOT-22 total and nasal-domain scores, nasal peak inspiratory flow, rhinosinusitis visual analogue scale, and adverse events. The posted record lists 8 secondary outcomes. Assessing many outcomes creates a multiplicity question: in general, the chance of at least one nominally small p-value can increase when many hypotheses are tested.

How that issue was handled is not reported in the registry record. The record does not describe a testing hierarchy, multiplicity adjustment, or whether secondary outcomes were treated as exploratory. The primary comparison's p-value should therefore be read as the result for that comparison, not as proof that every listed outcome meets a prespecified statistical standard. The registry's primary endpoint designation identifies its central measure but does not by itself explain the full testing strategy.

The primary outcome population is described as the ITT analysis set, including all randomized participants, with only those who had Week 24 data reported. This makes the handling of missing outcome data important. Reasons for missing Week 24 measurements, the method used to address missingness, and sensitivity analyses are not reported in the registry record. The reported endpoint counts are n=172.0 and n=165.0, but the registry does not provide a participant-level account of missingness or its possible relationship to outcomes.

In general, an ITT principle aims to preserve randomized group assignment in analyses, while missing measurements can still require assumptions or statistical methods. Calling the analysis set ITT does not, on its own, explain how unavailable endpoint values were treated. The degree to which the result is sensitive to missing data cannot be determined from the posted description.

The trial's sample-size justification and any interim analyses are not reported in the registry record. The planning illustration is based on the observed effect and specified planning assumptions; it is not a substitute for a prospective design rationale or evidence of observed power.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (1.2%), atrial fibrillation (0.6%), eosinophilic granulomatosis with polyangiitis (0.6%), appendicitis (0.6%), neuroborreliosis (0.6%).

The registry reports serious adverse events for 3 participants in the dupilumab group, with 179 at risk, and for 7 participants in the omalizumab group, with 173 at risk. It reports other adverse events for 48 participants in the dupilumab group, with 179 at risk, and for 53 participants in the omalizumab group, with 173 at risk. Deaths are recorded as 0 in each group. These are the registry's reported counts; no rates or between-group safety tests are reported.

The registry also lists serious adverse-event terms with percentages: pneumonia, 1.2%; atrial fibrillation, 0.6%; eosinophilic granulomatosis with polyangiitis, 0.6%; appendicitis, 0.6%; neuroborreliosis, 0.6%; and contusion, 0.6%. These percentages are reported as posted and should not be read as comparative estimates. The record does not give a statistical comparison for these terms.

In general, adverse-event counts describe events recorded during follow-up; they do not by themselves establish that a treatment caused an event. Counts also do not show event timing, duration, recurrence or severity beyond the registry's serious-event classification. The safety summary should be interpreted separately from the primary efficacy endpoint, and the registry does not report enough detail to assess all safety differences between groups.

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

The central statistical result is a Week 24 between-group difference in change in nasal polyp score. The reported ANCOVA estimate is -1.60, with a 95% confidence interval from -1.96 to -1.25 and p < 0.001. Given the score's direction, negative change indicates reduced polyp severity, and the negative contrast indicates a larger average reduction in the dupilumab group than in the omalizumab group under the reported analysis.

This is an estimate about a group-level score in the trial's stated population and at the stated follow-up time. It is not a prediction for an individual participant. The interval describes uncertainty in the estimated contrast under the analysis, not the full range of individual responses. The result also does not tell how many participants improved, since no responder threshold or responder count is reported for the primary endpoint.

Statistical evidence and clinical importance are related but distinct. The reported p-value is small under the comparison's null hypothesis, while the clinical importance threshold for NPS is not reported in the registry record. The result alone therefore cannot establish whether the difference is large enough to matter to patients. The model covariates are also not reported, which limits independent assessment of the adjusted comparison.

The primary outcome does not answer every question raised by the trial. The study listed smell, symptom, quality-of-life, airflow and safety outcomes, but each requires its own estimates and uncertainty. Nor does the result establish what happens beyond the 24-week treatment period or in populations other than people with severe CRSwNP and comorbid asthma. Such conclusions are not reported in the registry record.

In general, a randomized head-to-head estimate is designed to compare assigned groups within the trial, but interpretation still depends on outcome availability, analysis choices and the study's conduct. The record's description of Week 24 data and its limited reporting of missing-data methods leave some uncertainty about those aspects. The finding should be read as the posted statistical result for this primary endpoint, not as a complete summary of all clinical outcomes.

14. Why This Trial Matters Statistically

This trial is statistically informative because it directly compares two active treatments using a prespecified primary measure of nasal polyp severity. Rather than relying only on separate within-group changes, the registry reports an ANCOVA contrast between groups, with a confidence interval and p-value. That direct comparison addresses a different question from whether each group's score changed from baseline.

The endpoint also illustrates the importance of direction. NPS ranges from 0 to 8, and higher scores indicate more extensive or severe polyps. Since negative change means less severity, the sign of the between-group estimate can be interpreted only with the scale definition in view. Reporting both the group estimates and the adjusted contrast helps distinguish absolute change within each group from comparative change between groups.

The record also makes visible questions that are central to trial interpretation: how a model-based estimate relates to the group summaries, who contributed Week 24 endpoint data, and what is known about multiplicity and missing outcomes. The ITT analysis-set description does not eliminate the need to understand endpoint availability. Likewise, a small p-value is not a substitute for an effect-size interval or a clinically meaningful threshold.

Finally, the registry lists a range of secondary patient-reported and functional outcomes alongside safety outcomes. These broaden the clinical questions, but their interpretation depends on their own results and on how multiple analyses were handled. The primary result is a focused comparison of NPS at Week 24; it cannot stand in for a complete account of symptoms, quality of life or safety.

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 registry record does not report the covariates or full specification of the ANCOVA model. This limits the ability to judge the adjustment or reproduce the comparison from the posted summary. The primary endpoint is reported only for participants with Week 24 data, while the description of the ITT set includes all randomized participants. Reasons for unavailable endpoint data and the missing-data method are not reported in the registry record.

The clinical-importance threshold for NPS is not reported, so the estimate cannot be translated into a threshold-based judgment about patient importance. The registry also does not report a responder analysis for the primary endpoint. Although multiple secondary outcomes are listed, the multiplicity strategy and the status of those analyses as confirmatory or exploratory are not reported.

The record lists the trial as completed and gives primary completion timing, but the results summarized for the primary endpoint concern Week 24. Longer-term results are not reported in the registry record. The registry describes a triple-masked randomized trial, but fuller details of masking implementation, adherence, protocol deviations and treatment discontinuation are not reported.

The sample-size planning illustration uses the observed effect and should not be treated as a prospective design justification or observed power. The original sample-size rationale and any interim-analysis plan are not reported. Safety counts are posted, but the registry summary does not provide comparative statistical tests or detailed timing and duration for events. These reporting limits do not negate the primary estimate; they define what can and cannot be assessed from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients — NCT04998604.
• Registry record last updated 2025-10-23; status last verified 2025-09.
• Results first posted 2025-10-23.
• 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

NCT04998604 is a completed Phase 4 randomized, parallel-group, triple-masked comparison of dupilumab and omalizumab in severe CRSwNP with comorbid asthma. The primary endpoint was change from baseline to Week 24 in nasal polyp score, assessed by nasal endoscopy. Negative change represents lower polyp severity.

The registry reports least-squares mean changes of -2.65 for dupilumab and -1.05 for omalizumab. The ANCOVA difference is -1.60, with a 95% confidence interval from -1.96 to -1.25 and p < 0.001. Endpoint counts are n=172.0 and n=165.0, respectively; only participants with Week 24 data are reported for this outcome.

The registry lists secondary symptom, quality-of-life, airflow and safety outcomes. Details of multiplicity handling, missing-data methods, the ANCOVA covariates and the clinical-importance threshold for NPS are not reported in the registry record.