Effect of Mepolizumab in Severe Bilateral Nasal Polyps: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Mepolizumab in Severe Bilateral Nasal Polyps (NCT03085797), a randomized phase 3 study. The primary outcome is Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 52.

2. Clinical Question

The study was randomized, double-blind, parallel-group, and phase 3. The registry record describes independent reviewers who were blinded to treatment and assessed nasal endoscopy recordings. This clinical question is about a measured change in endoscopic scores during the trial, not a complete account of symptoms, function, safety, or longer-term outcomes. Those considerations include other recorded outcomes, but their evidence is not equivalent to the primary endpoint.

3. Trial Design

SYNAPSE was a randomized, double-blind, parallel-group phase 3 study of mepolizumab as an add-on to maintenance treatment in adults with severe bilateral nasal polyps. The registry record lists an enrollment of 414. It gives the study start as 2017-05-25, primary completion as 2019-12-11, and status as completed. These dates describe the registry record; they do not establish the timing of every analysis or data-processing decision.

The brief summary describes a 4-week run-in period followed by randomization to a 52-week treatment period. Participants received mepolizumab 100 mg or matching placebo by subcutaneous injection every 4 weeks, alongside standard care that included daily mometasone furoate. The arm descriptions specify thirteen doses during the treatment period. The registry describes triple masking, but does not report further detail about which study roles were masked.

The primary endpoint was change from baseline in total endoscopic nasal polyp score at Week 52. The analysis population was described as participants who were randomized and took at least 1 dose of study treatment. The endpoint description says that data up to Week 52, including data from participants who remained in the study after early discontinuation from investigational product, were included. It does not describe the analysis population or missing-data approach in greater detail.

Enrollment is a study-level registry figure, not the denominator for every endpoint. The posted primary outcome lists group counts of 201 for placebo and 206 for mepolizumab. Outcome-specific denominators and analysis populations can differ, so counts should be interpreted in the context of the particular outcome rather than assumed to apply to all trial measures.

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 414 participants were enrolled and randomized in the study, of which only 407 participants received study treatment and were included in the Intent-to-Treat Population (defined as all randomized participants who took at least 1 dose of study treatment). Seven participants did not receive study treatment as they were randomized in error.

Treatment Period (TP) (52 Weeks)

Reasons for not completing this period:

No-treatment Follow-up Period (6 Months)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population which included all randomized participants who took at least 1 dose of study treatment.

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.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 52, measured over Baseline (Day 1) and Week 52.

The primary endpoint was change from baseline in total endoscopic nasal polyp score at Week 52. Independent reviewers, blinded to treatment, reviewed recordings of nasal endoscopies and scored the right and left nostrils according to polyp size. Each nostril score ranged from 0 to 4, and the total score ranged from 0 to 8. Higher scores indicate greater disease severity.

The score provides a structured, observer-assessed measure of polyp burden. Using an explicit scoring scale makes it possible to describe change in endoscopic findings over the treatment period rather than relying only on a general impression. The endpoint description defines change as the post-baseline value minus the baseline value; thus, a negative change represents a lower score at follow-up than at baseline. This interpretation concerns the direction of the score, not a conclusion about the overall clinical value of treatment.

The registry reports the group results as medians with full ranges and gives a between-group difference in medians. Median-based summaries can describe the center of a distribution without assuming that values are symmetrically distributed. The endpoint description also states that data up to Week 52 were included for participants who remained in the study after early discontinuation from investigational product. It does not explain how missing Week 52 scores were handled, or how the endpoint relates to other aspects of disease experience. The endoscopic score is one defined outcome, not a complete measure of symptoms, quality of life, or safety.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome was summarized using medians and full ranges, and the between-group analysis used a Wilcoxon rank-sum test. The registry reports a difference in medians and its 95% confidence interval. These summaries and the test are designed for comparison of distributions without requiring the same modeling assumptions as a comparison of means under a normal-distribution model.

What does the confidence interval convey?

A confidence interval communicates uncertainty around an estimated contrast. In repeated use of a procedure with the same assumptions, intervals would vary from sample to sample; the stated confidence level describes the procedure’s long-run coverage. It does not mean that a particular interval has a 95% probability of containing the true effect. For this result, the interval is from -1.11 to -0.34, and its position relative to zero is consistent with the reported test result. Precision is not the same as clinical importance: the interval describes statistical uncertainty, while judgments about meaningful change require clinical context not quantified by the interval alone.

Why use a rank-based test?

The Wilcoxon rank-sum test compares the relative ordering of observations between groups. It can be useful when an outcome is ordinal or its distribution does not support a simple mean-based model. It does not, by itself, test a difference in medians in every possible distributional setting; interpreting its estimate specifically as a median difference depends on how the outcome distributions relate to one another. The registry labels the reported contrast as a difference in medians and reports the test used. Details of any additional assumptions or supporting diagnostics are not reported in the registry record.

How should the secondary binary result be read?

For the outcome of at least one course of systemic steroids for nasal polyps up to Week 52, the registry reports participant percentages and a sponsor analysis using logistic regression. The posted regression result is an odds ratio of 0.58, with a 95% confidence interval from 0.36 to 0.92 and p = 0.020. An odds ratio compares odds, not probabilities; it should not be described as a risk ratio or as a percentage reduction in probability.

A separate, simple unadjusted recalculation from the posted counts expresses the contrast as a risk difference. The recalculated estimate is -0.116, with a 95% confidence interval from -0.205 to -0.026 and an unadjusted p-value of 0.012. This is a difference in proportions on the probability scale, not the same estimand as the logistic-regression odds ratio. The two analyses can differ because they use different measures and modeling approaches. The registry record does not describe the covariates or other details of the sponsor’s logistic model.

What do the sample-size illustrations mean?

Planning illustrations based on an observed effect are not observed power and are not the trial’s original design justification. They show the approximate participants per arm for 80% power and for 90% power if a future study were designed to detect the stated fraction of the observed effect, using the listed assumptions. The record specifies a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustrations list 250 and 334 participants per arm for planning for 100% of the observed effect; 456 and 610 for planning for 75% of the observed effect; and 1,050 and 1,405 for planning for 50% of the observed effect, respectively for 80% and 90% power. These are planning scenarios, not observed participant counts or a statement about the probability that this trial detected an effect.

Smaller effects require more information to distinguish them from random variation under a fixed design framework. This is a general statistical principle, not evidence that the trial was planned using these calculations. The sample-size justification for the trial is not reported in the registry record. The registry record also does not report an interim-analysis plan, a complete prespecified statistical analysis plan, or a multiplicity procedure. Those omissions limit how fully the posted p-values and secondary results can be placed in the context of the original analysis plan.

10. Analyses Reported by the Sponsor

For the primary endpoint, the registry reports the sponsor’s comparison as a Wilcoxon rank-sum test, with a difference in medians of -0.73, a 95% confidence interval from -1.11 to -0.34, and p < 0.001. There is no discrepancy flagged between that posted analysis and the outcome information used in this reading. The sponsor’s own analysis therefore remains the primary analysis to interpret; the group medians and ranges provide descriptive context rather than replacing it.

For the secondary systemic-steroid outcome, the sponsor’s reported analysis is logistic regression, giving an odds ratio of 0.58, a 95% confidence interval from 0.36 to 0.92, and p = 0.020. The unadjusted recalculation uses the posted group counts to estimate a risk difference and its interval. It is a transparent complementary calculation, not a correction to or substitute for the sponsor’s model. Because odds ratios and risk differences are different measures, numerical agreement is not expected.

The registry record does not provide enough detail to reconstruct the sponsor’s models or assess every analysis decision. In particular, it does not report the full model specification for the secondary result or a complete statistical analysis plan. The recalculated secondary result should therefore be understood as a simple unadjusted comparison, while the sponsor’s reported analysis takes precedence as the trial’s own analysis.

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when an analysis considers several outcomes, time points, or comparisons. Even if each test uses a conventional significance threshold, repeated testing can increase the chance of finding a nominally notable result by chance. The study has a primary outcome and multiple secondary outcomes, but a multiplicity strategy, such as adjustment or a prespecified sequence for testing, is not reported in the registry record. As a result, the primary endpoint and secondary outcomes should not be given interchangeable evidential weight, and secondary p-values should be interpreted cautiously.

Missing data can also affect interpretation. The primary endpoint description says that data up to Week 52 were included, including data from participants who remained in the study after early discontinuation from investigational product. This indicates that the stated analysis was not limited to data collected while participants continued investigational product. However, the registry record does not report how missing Week 52 scores were handled, whether imputation was used, how the timing of discontinuation was incorporated, or whether sensitivity analyses assessed the effect of missing outcomes.

The primary analysis population is described as the ITT Population, defined in the registry as randomized participants who took at least 1 dose of study treatment. The record does not provide enough information to determine how participants who did not take a dose were handled in every analysis, or whether other analysis populations were used. The secondary outcome information likewise does not fully specify denominators and missing-data procedures for every measure.

A detailed statistical analysis plan, prespecified multiplicity approach, interim-analysis information, and sample-size justification are not reported in the registry record. Their absence does not demonstrate that these procedures were not used; it means that they cannot be evaluated from the registry information. These gaps limit assessment of how closely the posted analyses follow the planned inferential framework.

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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (1.5%), asthma (1.5%), myocardial infarction (1.5%), pulmonary embolism (1.5%), duodenal ulcer (1.5%).

During the treatment period, the registry lists serious adverse events in 14 participants in the placebo group, with 201 at risk, and 12 participants in the mepolizumab group, with 206 at risk. Other adverse events are listed for 141 participants in the placebo group and 139 participants in the mepolizumab group. The record lists 0 deaths in each group during the treatment period.

During follow-up, the registry lists serious adverse events in 4 participants in the placebo group, with 65 at risk, and 2 participants in the mepolizumab group, with 69 at risk. Other adverse events are listed for 13 participants in the placebo group and 14 participants in the mepolizumab group. The record lists 1 death in the placebo group and 0 in the mepolizumab group during follow-up.

These are counts within the registry’s treatment-period and follow-up groupings. They do not by themselves establish that an event was caused by the assigned treatment, and the group counts should not be treated as a complete comparative safety analysis. The registry lists anaemia, asthma, myocardial infarction, pulmonary embolism, duodenal ulcer, and urticaria among the top serious-event terms, each at 1.5%. The record does not provide the full clinical context, timing, or attribution needed to interpret individual events.

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

The primary result describes a difference between randomized groups in change from baseline in an endoscopic score at Week 52. The group medians and the reported difference in medians are in the direction of a lower score for mepolizumab than for placebo. The confidence interval and p-value describe statistical uncertainty and the result of the reported test. They do not quantify every clinically relevant consequence or establish what any particular participant experienced.

The score is an observer-assessed measure of polyp size based on nasal endoscopy. It is not, on its own, a measure of all symptoms, quality of life, need for procedures, or safety. Other outcomes were registered, but detailed comparative information is not reported for all of them in the record summarized for this analysis. The primary finding therefore should not be expanded into claims about every outcome or every aspect of care.

A statistically notable result is not synonymous with a clinically important result. The registry reports the score’s scale and direction, but does not report a threshold for a clinically meaningful between-group difference. The confidence interval indicates the precision of the estimated contrast under the analysis, not the likelihood that an individual will experience a particular change.

The findings apply to the registered study and its described population, treatment context, endpoint, and follow-up. They do not establish effects in populations or settings not described, nor do they answer questions about longer-term outcomes not reported in the registry record. The safety counts also require context and cannot establish causation from counts alone. This interpretation is statistical, not medical advice.

14. Why This Trial Matters Statistically

This trial illustrates how a continuous or ordered clinical measure can be analyzed using a rank-based method and summarized with medians and ranges. The endpoint’s scale gives direction to the result: lower scores indicate less disease severity, while the analysis compares change between treatment groups rather than treating a within-group change as the treatment effect. That distinction is fundamental in randomized trials.

It also shows why effect estimates and uncertainty intervals should be read together. The estimate gives a direction and magnitude on the reported scale; the interval shows the range of values compatible with the analysis. A p-value alone cannot describe precision, clinical importance, or the distribution of individual outcomes.

The registered secondary steroid outcome provides a useful statistical contrast between an odds ratio from logistic regression and an unadjusted risk difference recalculated from counts. These measures answer related but different questions. They should not be conflated, and the recalculation does not supersede the sponsor’s own analysis. The comparison highlights the importance of stating the effect measure and model rather than treating all relative or absolute measures as interchangeable.

Finally, the registry record makes visible limits on interpretation: it does not report a complete multiplicity strategy, detailed handling of missing values, or the trial’s sample-size justification. Such information matters because analysis choices affect how results should be interpreted, particularly when several outcomes are considered. The trial is therefore a useful example of reading a primary result carefully while keeping secondary evidence, safety counts, and registry reporting gaps in their proper context.

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 contains a clear description of the primary score but limited detail about analysis implementation. It does not report the full statistical analysis plan, the handling of missing Week 52 scores, or sensitivity analyses for missing data. The endpoint description includes data after early discontinuation from investigational product for participants remaining in the study, but does not explain how all other incomplete follow-up was treated.

Although the primary population is called ITT, its stated definition includes randomized participants who took at least 1 dose. The record does not clarify how the analysis addressed randomized participants who did not take a dose, or describe other analysis populations. This limits evaluation of how the analysis population relates to the randomized groups.

The primary endpoint uses an ordinal-style score and a rank-sum test, but additional diagnostics or distributional details are not reported in the registry record. Group full ranges do not show the shape of the data or how observations were distributed within each group. The record also does not state a threshold for a clinically meaningful score difference.

Several secondary outcomes are named, but detailed comparative results are not available for all of them in the information summarized. The multiplicity plan is not reported, so the role of secondary p-values in a planned testing sequence cannot be assessed. For the systemic-steroid outcome, the sponsor’s logistic-regression specification is not reported, while the recalculation is explicitly unadjusted and uses a different measure.

The safety information is presented as event counts in treatment and follow-up groupings. Further detail about event timing, seriousness criteria, attribution, and participant-level overlap is not reported in the registry record. These limitations constrain interpretation and do not establish that unreported analyses or procedures were absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Mepolizumab in Severe Bilateral Nasal Polyps — NCT03085797.
• Registry record last updated 2026-07-22; status last verified 2026-07.
• Results first posted 2020-12-17.
• 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

NCT03085797 is the completed SYNAPSE phase 3 randomized, double-blind, parallel-group study of mepolizumab 100 mg added to maintenance treatment for adults with severe bilateral nasal polyps. The trial compared subcutaneous mepolizumab with matching placebo, alongside standard care including daily mometasone furoate.

The primary outcome was change from baseline in total endoscopic nasal polyp score at Week 52. The posted medians were 0.0 for placebo and -1.0 for mepolizumab; the reported difference in medians was -0.73, with a 95% confidence interval from -1.11 to -0.34 and p < 0.001. The score’s higher values indicate greater disease severity.

The registry also lists secondary symptom, quality-of-life, surgery, and steroid-use outcomes, along with adverse-event counts. Detailed comparative results are not reported for every secondary outcome. Multiplicity procedures, complete missing-data methods, and the trial’s sample-size justification are not reported in the registry record.