This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Open-label Study of Dupilumab in Patients With Atopic Dermatitis (NCT01949311), a na phase 3 study. The primary outcome is Number of Treatment Emergent Adverse Events (TEAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01949311 |
| Phase | Phase 3 |
| Condition | Atopic Dermatitis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 2733 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Regeneron Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Adults with atopic dermatitis who participated in previous dupilumab clinical trials. The safety analysis set includes patients who received any study drug, analyzed according to treatment received.
Intervention
Repeat doses of dupilumab. The study also describes an optional sub-study assessing a switch from the current dupilumab drug product to a new drug product.
Comparator
There is no separate comparator group in this single-group study. Allocation is listed as not applicable and masking as none, so the record does not describe a randomized, blinded treatment comparison.
Primary question
What number of treatment-emergent adverse events was observed during long-term dupilumab treatment, over a timeframe of up to 272 weeks? The stated primary objective is to assess long-term safety.
The study also addresses immunogenicity in the context of retreatment and monitors efficacy parameters associated with long-term treatment. The optional sub-study has separate objectives concerning safety after switching drug products, systemic exposure and immunogenicity. These objectives do not create a comparison with an untreated or alternative-treatment group in the main study.
The registry describes participants as adults with atopic dermatitis who took part in previous dupilumab clinical trials. The study therefore concerns continued or repeated treatment in that context; it is not described as a trial enrolling a treatment-naive population. The registry record does not report a randomized allocation or a masked assessment process.
The primary question is about the count of treatment-emergent adverse events, not a treatment effect relative to another group. The posted record does not report the result for that primary endpoint. It also does not report comparative estimates for the secondary efficacy outcomes, such as EASI or IGA measures. Accordingly, the clinical question can be stated from the objectives, but the registry record does not provide the outcome estimates needed to quantify the observed response or compare treatment strategies.
3. Trial Design
This is a Phase 3, open-label study with a single-group model. The intervention is dupilumab, and the arm description states that participants receive repeat doses. Allocation is listed as not applicable, and masking is listed as none. The registry lists enrollment of 2733 and the condition as atopic dermatitis. The study status is completed.
The registry dates the study start to 2013-10-10 and primary completion to 2022-06-27. The primary outcome timeframe is up to 272 weeks. These dates and the stated timeframe describe the record; they do not establish how long any individual participant was followed or how much treatment exposure each participant contributed.
The primary objective is long-term safety assessment. Secondary objectives include assessment of immunogenicity in the context of retreatment and monitoring efficacy parameters associated with long-term treatment. An optional sub-study concerns safety after switching from the current dupilumab drug product to a new drug product, with systemic exposure and immunogenicity as additional objectives. The registry lists dupilumab as the intervention but does not provide a separate comparator intervention.
The safety analysis set is defined as patients who received any study drug, based on treatment received. This is an as-treated population definition, not an intention-to-treat definition based on assignment. The adverse-event record gives an at-risk count of 2677 for serious events and 2677 for other events. That count is distinct from the registry enrollment figure and is the relevant stated denominator for those safety summaries; the registry does not explain the difference between the figures.
The record lists 24 outcome measures and zero analyses. It does not report a randomization procedure, a concurrent control group, or a statistical analysis plan. Details such as dose schedules, adherence, participant flow, follow-up distribution and reasons for discontinuation 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 1297 participants completed the study and 1380 participants had withdrawn. Withdrawal from study included study terminated by the Sponsor (708), and withdrawal by the participant (375), Adverse Event (107), Lost to Follow-Up (73), Lack of Efficacy (50), Protocol Deviation (34), Pregnancy (20), Physician Decision (9), and reasons not specified (4)
Overall Study
| Stage | Dupilumab |
|---|---|
| STARTED | 2677 |
| COMPLETED | 1297 |
| NOT COMPLETED | 1380 |
Reasons for not completing this period:
| Reason | Dupilumab |
|---|---|
| Lost to Follow-up | 73 |
| Terminated by Sponsor | 708 |
| Withdrawal by Subject | 375 |
| Lack of Efficacy | 50 |
| Protocol Deviation | 34 |
| Pregnancy | 20 |
| Physician Decision | 9 |
| Other | 4 |
| Adverse Event | 107 |
Analysis population for the primary outcome, as defined in the registry: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).
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.
| Characteristic | Unit | Dupilumab |
|---|---|---|
| Participants analysed | 2677 | |
| Age, Continuous | Years | 39.2 (SD 13.42) |
| Sex: Female, Male: Female | Participants | 1066 |
| Sex: Female, Male: Male | Participants | 1611 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 94 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2532 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 51 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 541 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 147 |
| Race (NIH/OMB): White | Participants | 1936 |
| Race (NIH/OMB): More than one race | Participants | 33 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Treatment Emergent Adverse Events (TEAEs), measured over Up to 272 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Number of Events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of treatment-emergent adverse events, measured as a number of events over a timeframe of up to 272 weeks. Treatment-emergent describes events recorded after treatment begins within the study’s outcome framework; it does not by itself establish that treatment caused an event. The registry specifies that the safety analysis set includes all patients who received any study drug and is based on treatment received.
A count endpoint can describe the recorded burden of events during a study, which is relevant to a long-term safety objective. However, a count alone does not indicate how many participants experienced an event, how often events recurred in the same participant, how severe events were, or how much time each participant was observed. Those distinctions matter because the same count can have different interpretations under different patterns of recurrence and follow-up.
The registry does not report a numerical result for this primary endpoint, its dispersion, or an estimate of event rates over person-time. It therefore does not allow readers to quantify the primary event count from the posted record. The separately listed adverse-event summaries provide counts of participants affected and selected serious-event terms, but they are not a reported result for the primary count endpoint.
In general, safety endpoints are used to organize and describe events observed during treatment, rather than to prove that every recorded event was caused by the study drug. Interpretation depends on definitions, observation time, event ascertainment and the analysis population. Further endpoint definitions and analysis details are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted record identifies a long-term safety study of dupilumab in adults with atopic dermatitis and reports selected adverse-event summaries. It does not report the primary endpoint result, which is the number of treatment-emergent adverse events over a timeframe of up to 272 weeks. A primary endpoint objective is not itself an outcome estimate: without the result, readers cannot determine the recorded total for that endpoint from the registry record.
The adverse-event summary reports 283 participants affected by serious adverse events among 2677 at risk, and 1613 affected by other adverse events among 2677 at risk. The record also reports 3 deaths. These are descriptive safety figures. They do not establish whether events were caused by dupilumab, and they are not comparisons against a control group. The serious-event terms listed with their reported frequencies include osteoarthritis at 0.4%, squamous cell carcinoma of skin at 0.3%, appendicitis at 0.2%, dermatitis atopic at 0.2%, ligament rupture at 0.2%, and syncope at 0.2%.
Because the study has a single group and no stated comparator, these figures cannot estimate the difference in risk between dupilumab and another treatment or no treatment. A count of affected participants also does not disclose recurrence, severity distribution beyond the serious-event classification, timing, duration, or individual exposure. The registry does not report person-time, so the posted counts cannot be interpreted as event rates per unit of exposure.
The study’s objectives also include immunogenicity and efficacy monitoring. The registry lists secondary outcome measures concerning IGA, EASI and disease activity, among others, but does not report their results in the record summarized by these registry entries. Without those estimates, no conclusion about changes in disease measures can be drawn from the listed outcomes alone.
The record reports zero analyses. It does not identify a statistical model, adjustment approach, or inferential estimate for the outcomes. The absence of comparative analyses is consistent with the single-group design, but it leaves the safety summaries descriptive rather than comparative. In general, confidence intervals would express the precision of an estimate under a specified statistical model; no such intervals are reported for the adverse-event summaries in this record.
Overall, the registry supplies a study structure and selected safety counts, but not a numerical result for the primary endpoint or estimates for the secondary outcomes. The counts can be read as observations recorded in the study population, not as proof of causation or as comparative evidence.
9. Statistical Methods Explained
The registry describes a single-group, open-label study. In general, a single-group study records outcomes among participants receiving the study intervention without a concurrent comparison group. This design can describe observations during treatment, but it cannot separate treatment-associated changes from changes that might have occurred over time, from the underlying condition, or from other influences. Open-label means masking is not used; the registry lists masking as none.
The primary outcome is a count of treatment-emergent adverse events. A count is not interchangeable with a count of affected participants: one person may experience more than one event, and the number of events can therefore differ from the number of people with events. The adverse-event summary reports affected-participant counts for serious and other events, while the primary endpoint is described as number of events. The registry does not report the primary event count or explain how repeated events were handled.
In general, count outcomes may show over-dispersion, meaning that variability exceeds what a simple count model would expect. This can arise, for example, when event counts vary greatly across participants or when events recur within some participants. If over-dispersion is present, a model that assumes less variability can produce uncertainty estimates that are too narrow. This is a general statistical consideration, not a claim that the study used a particular model or that over-dispersion was observed. The registry record does not report a count model, dispersion estimate, or method for handling recurrent events.
Follow-up time is also relevant to safety counts. Participants observed for longer have more opportunity to experience or report events. In general, event rates account for exposure time, whereas a raw count does not. The record gives a maximum outcome timeframe of up to 272 weeks, but does not report the distribution of follow-up or person-time. It is therefore not possible to derive or interpret person-time rates from the posted summaries.
The safety analysis set includes all patients who received any study drug and is based on treatment received. In general, an as-treated population groups observations according to treatment actually received, while an intention-to-treat approach ordinarily preserves original assignment regardless of treatment received. Because this study is described as single-group with allocation not applicable, the registry’s stated safety definition is the relevant population information; it does not report additional analysis populations.
The registry states that the trial has 24 outcome measures and zero analyses. This means the record lists outcome measures without reporting analyses in the data. The existence of an endpoint definition does not imply that its result, uncertainty interval, or statistical test is posted. The record does not report a detailed analysis plan, model specifications, covariate adjustment, handling of missing observations, or rules for selecting among multiple analyses.
The record also includes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses the total number of events under the Schoenfeld approach; for other outcomes, it describes participants per arm. These are planning assumptions, not the trial’s own design or observed power. They should not be read as evidence that this single-group study had two randomized arms. No planning result values are reported in the registry record.
In general, a confidence interval gives a range of values compatible with an estimate under the assumptions of the statistical method. Its width reflects precision: wider intervals indicate greater uncertainty, while narrower intervals indicate more precision. A p-value, when reported, addresses compatibility of data with a specified null model; it is not a measure of clinical importance or the probability that a treatment works. The registry record does not report confidence intervals or p-values for these outcomes, so neither precision nor statistical significance can be assessed from the record.
Multiplicity arises when many outcomes or analyses are considered. In general, testing multiple hypotheses can increase the chance of at least one apparently unusual result if no adjustment or prespecified hierarchy is used. The registry lists 24 outcome measures but does not report a multiplicity strategy or analysis results. This does not establish that multiplicity was or was not addressed in sponsor analyses; the method is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 24 outcome measures, including the primary count of treatment-emergent adverse events and secondary measures concerning serious and other adverse events, immunogenicity, IGA, EASI and disease activity. It reports zero analyses. The record therefore does not provide estimates or inferential results across this outcome set.
When a study evaluates multiple outcomes or performs multiple analyses, the chance of finding at least one apparently notable result can increase. General approaches include prespecifying a hierarchy, controlling an overall error rate, or treating findings as exploratory. The registry record does not report whether any such approach was planned or used. It also does not report a prespecified testing sequence, adjustment method, or distinction between confirmatory and exploratory analyses.
The record defines the safety analysis set as patients who received any study drug, analyzed according to treatment received. It does not report how missing outcome data were handled, whether participants with incomplete follow-up were included in each measure, or how discontinuation affected analysis. These omissions limit assessment of potential bias: missingness can be related to health status, treatment exposure or the likelihood that an outcome is observed. General statistical methods can address some missing-data patterns, but their assumptions require information about the reasons and timing of missingness.
Participant flow, the number contributing to each outcome, and the amount of follow-up by participant are not reported in the registry record. The enrollment figure of 2733 should not be treated as the denominator for every outcome; the safety summaries separately state 2677 at risk. No further outcome-specific denominators are reported.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Dupilumab | 283 | 2677 | 10.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dupilumab | 3 of 2677 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dupilumab | 1613 of 2677 |
Most frequent serious adverse event terms
| Event term | Organ system | Dupilumab |
|---|---|---|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 11 of 2677 |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 8 of 2677 |
| Appendicitis | Infections and infestations | 6 of 2677 |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | 6 of 2677 |
| Ligament rupture | Injury, poisoning and procedural complications | 5 of 2677 |
| Syncope | Nervous system disorders | 5 of 2677 |
| Inguinal hernia | Gastrointestinal disorders | 5 of 2677 |
| Ankle fracture | Injury, poisoning and procedural complications | 4 of 2677 |
| Nasal septum deviation | Respiratory, thoracic and mediastinal disorders | 4 of 2677 |
| Depression | Psychiatric disorders | 4 of 2677 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dupilumab |
|---|---|---|
| Nasopharyngitis | Infections and infestations | 774 of 2677 |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | 446 of 2677 |
| Upper respiratory tract infection | Infections and infestations | 365 of 2677 |
| Conjunctivitis | Infections and infestations | 277 of 2677 |
| Conjunctivitis allergic | Eye disorders | 242 of 2677 |
| Headache | Nervous system disorders | 218 of 2677 |
| Oral herpes | Infections and infestations | 200 of 2677 |
| Injection site reaction | General disorders | 138 of 2677 |
Serious events with the highest arm-level rate: osteoarthritis (0.4%), squamous cell carcinoma of skin (0.3%), appendicitis (0.2%), dermatitis atopic (0.2%), ligament rupture (0.2%).
The registry reports 283 participants affected by serious adverse events among 2677 at risk. For other adverse events, it reports 1613 participants affected among 2677 at risk. It also reports 3 deaths. These figures describe the posted safety summaries; they are not an estimate of the causal effect of dupilumab because the study has no separate comparator group.
The listed serious-event terms and reported frequencies are osteoarthritis, 0.4%; squamous cell carcinoma of skin, 0.3%; appendicitis, 0.2%; dermatitis atopic, 0.2%; ligament rupture, 0.2%; and syncope, 0.2%. The registry does not report further detail about these terms, such as timing, participant characteristics, recurrence, or an assessment of whether each event was related to treatment.
In general, an affected-participant count is different from an event count: a participant can experience multiple events. The primary endpoint is defined as the number of treatment-emergent adverse events, but its result is not reported in the registry record. The serious and other adverse-event summaries should therefore be read as descriptive counts of affected participants, not as a substitute for the missing primary event-count result.
The at-risk denominator indicates the population stated for the summaries, but the record does not give person-time or follow-up distribution. These counts do not show how event occurrence varied with duration of exposure.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this completed Phase 3 study was designed to monitor long-term safety in adults with atopic dermatitis receiving repeat doses of dupilumab. It also identifies objectives concerning immunogenicity and efficacy monitoring, plus an optional drug-product switching sub-study. The record gives selected safety counts and serious-event terms, but does not report the primary endpoint result or results for the listed secondary efficacy outcomes.
The serious adverse-event summary reports 283 affected participants among 2677 at risk; the other adverse-event summary reports 1613 affected among 2677 at risk; and the record reports 3 deaths. These counts describe what was recorded in the study population. Without a concurrent comparator, they do not show how those outcomes compare with another treatment or with no study treatment. Without additional information, they also do not establish that the intervention caused an event.
The primary endpoint is a number of treatment-emergent adverse events, whereas the safety summary reports numbers of participants affected. Those measures answer different questions. The missing primary result means the posted record does not quantify the event count that the study designated as primary. The registry also does not report participant-level recurrence, exposure-adjusted rates, or uncertainty intervals for the safety figures.
The study’s single-group, open-label design is suitable for describing observations under the recorded treatment conditions, but it offers limited basis for causal comparisons. General clinical and statistical interpretation depends on outcome definitions, completeness of follow-up, event ascertainment, and the analysis population. The registry record does not report enough detail to assess all of those features.
Accordingly, the available information supports a description of the study’s objectives, design and selected adverse-event summaries. It does not support a comparative estimate of benefit or harm, a conclusion about treatment efficacy, or a precise estimate of the primary event burden. The unreported outcome results and analysis details should not be inferred from the completed status or from the presence of outcome definitions.
13. Why This Trial Matters Statistically
This study is statistically notable for asking a long-term safety question in a single-group, open-label setting. That design makes descriptive summaries central: the registry reports affected-participant counts and selected serious-event terms, but there is no concurrent comparator from which to estimate a between-group difference. Readers need to distinguish evidence about what was observed during study treatment from evidence about what treatment caused.
The primary endpoint is a count of treatment-emergent adverse events, while the posted safety summaries use affected-participant counts. These measures are not interchangeable. A count of events can include repeated events in the same participant, whereas an affected-participant count identifies people with an event. That distinction is important when assessing how a safety endpoint is represented and whether the reported result corresponds to the stated primary measure.
Long-term observation also raises questions about exposure and follow-up. A raw event count can reflect both event occurrence and the amount of time participants were observed. The record gives a maximum timeframe of up to 272 weeks but does not report person-time or the distribution of follow-up. An exposure-adjusted rate would answer a different question from a simple count, but no such rate is reported.
The record lists many outcome measures and reports zero analyses. This makes the separation between endpoint registration and reported statistical results especially important. Definitions identify what was intended to be measured; they do not provide estimates, precision, or evidence about the observed pattern. The absence of posted results also prevents assessment of how secondary outcomes relate to the safety objective.
Finally, the stated planning assumptions describe illustrations rather than the trial’s design. They should not be mistaken for a randomized comparison, a prespecified sample-size justification, or observed power. Clear reporting of analysis populations, follow-up, endpoint results and uncertainty would be needed for a fuller statistical interpretation.
14. 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 a numerical result for the primary endpoint, despite defining it as the number of treatment-emergent adverse events over a timeframe of up to 272 weeks. The listed safety counts do not fill that gap because they describe participants affected, not the primary event count. The record also reports zero analyses, so estimates, uncertainty intervals and statistical tests are not available for the outcomes described.
The single-group design has no concurrent control group, and the study is open-label. As a result, the posted counts cannot estimate comparative risks or distinguish treatment effects from other influences. The registry does not report a detailed event-ascertainment process or additional information about assessment of treatment relatedness.
The record does not report person-time, the distribution of follow-up, outcome-specific denominators, or how recurrent events were handled. Enrollment is listed as 2733, while the adverse-event summaries state 2677 at risk; the registry record does not explain this difference. The safety analysis set is defined as patients who received any study drug, but participant flow and reasons for non-inclusion or discontinuation are not reported.
Further limitations include the absence of reported missing-data methods, a detailed statistical analysis plan, and a multiplicity strategy. The registry lists efficacy and immunogenicity outcomes but does not report their results. These gaps prevent assessment of precision, robustness, and the relationship between safety observations and the study’s other objectives. They do not establish that the analyses were not conducted outside the registry record; those details are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open-label Study of Dupilumab in Patients With Atopic Dermatitis — NCT01949311.
- Registry record last updated 2023-10-17; status last verified 2023-10.
- 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.
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18. Record Summary
NCT01949311 is a completed Phase 3, open-label, single-group study of repeat dupilumab treatment in adults with atopic dermatitis who participated in previous dupilumab clinical trials. The registry lists enrollment of 2733 and gives a primary completion date of 2022-06-27. The primary objective is long-term safety assessment, with additional objectives concerning immunogenicity and efficacy monitoring.
The primary endpoint is the number of treatment-emergent adverse events over up to 272 weeks. Its result is not reported in the registry record. The safety summaries report serious adverse events in 283 participants among 2677 at risk, other adverse events in 1613 participants among 2677 at risk, and 3 deaths. No comparator group is described, and the record lists zero analyses. The posted information therefore supports descriptive reading of selected safety counts, but not a comparative treatment estimate or a full assessment of endpoint precision.