Etanercept Treatment in Patients With Moderate to Severe Plaque Psoriasis Who Lost Response to Adalimumab: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Etanercept Treatment in Patients With Moderate to Severe Plaque Psoriasis Who Lost Response to Adalimumab (NCT01543204), a na phase 4 study. The primary outcome is Percentage of Participants With an sPGA Score of 0 (Clear) or 1 (Almost Clear) at Week 12 by Anti-adalimumab Antibody Status.

2. Clinical Question

The primary endpoint focuses on a defined skin-assessment threshold at a specified visit. It asks whether participants reached a state rated clear or almost clear on the sPGA scale, and whether the reported percentage differed across anti-adalimumab antibody-status groups. The registry record describes the endpoint and its intended analysis population, but does not report the percentages, group sizes, confidence intervals, or the antibody-status-specific results. Consequently, it is possible to describe the question but not to determine the observed response pattern.

Because this was a single-group study, the primary question is descriptive of outcomes among participants receiving the etanercept regimen. It is not a randomized comparison of etanercept with another treatment or with no treatment. Any difference across antibody-status groups would also be a subgroup contrast, not a randomized treatment comparison. The record does not report enough results to assess such a contrast.

3. Trial Design

This was a phase 4, open-label, single-group study of etanercept in people with moderate to severe plaque psoriasis who had lost a satisfactory response to adalimumab. The study record lists an enrollment of 64. Amgen is identified as the sponsor. The study began on 2012-02-01, had a primary completion date of 2015-05-29, and is recorded as terminated. The reason for termination is not reported in the registry record.

Participants received etanercept 50 mg subcutaneously twice weekly for 12 weeks, followed by 50 mg subcutaneously once weekly for an additional 12 weeks. The primary endpoint was assessed at Week 12, at the end of the twice-weekly part of the stated regimen. The registry also lists multiple secondary outcomes involving sPGA scores and PASI 50 response at visits, including analyses by anti-adalimumab antibody status. These listed outcomes indicate the kinds of assessments specified in the record; the available record does not provide their outcome values.

The study had no masking, and allocation is listed as not applicable. This is consistent with the recorded single-group model: the record does not describe random assignment to treatment arms or a concurrent control group. Open-label status means participants and study personnel were not masked to the treatment assignment. General statistical context: without a control group, changes observed during follow-up cannot by themselves distinguish the effect of treatment from other influences, such as the natural course of disease, concurrent care, or changes in measurement. These limitations affect causal interpretation even when an outcome is reported.

The registry record lists 30 outcome measures and one analysis. It does not report a protocol-level statistical analysis plan, the reason the study was terminated, or a sample-size justification. Those details should not be inferred from the enrollment figure or from the outcome descriptions.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary analysis set (all participants who received at least one dose of investigational product during the study) with at least 1 post-baseline value. Participants with missing post-baseline data were imputed using the last observation carried forward (LOCF) method.

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 Percentage of Participants With an sPGA Score of 0 (Clear) or 1 (Almost Clear) at Week 12 by Anti-adalimumab Antibody Status, measured over Week 12.

The primary endpoint is the percentage of participants with an sPGA score of 0 (clear) or 1 (almost clear) at Week 12, reported by anti-adalimumab antibody status. The sPGA is described as a six-point scale ranging from 0 (clear) to 5 (very severe), used to assess disease severity through induration, scaling, and erythema. For this endpoint, a response means a score of 0 or 1. The registry identifies the primary analysis set as participants with available data.

A threshold-based endpoint translates a graded clinical assessment into a responder classification. This can make a result easier to interpret as the proportion reaching a stated clinical state, while also discarding distinctions among scores that fall on the same side of the threshold. Participants scoring 0 and 1 both count as responders for this definition; participants with higher scores do not meet the stated response definition.

General statistical context: a percentage communicates how common the defined outcome was in the analyzed group, while a confidence interval expresses uncertainty around that estimate. A confidence interval is especially useful because a percentage alone does not show how precisely the underlying response proportion has been estimated. Here the registry identifies a 95% confidence interval as the measure of dispersion, but the actual endpoint percentages and intervals are not reported in the registry record. The response frequency and its precision therefore cannot be evaluated from the available results.

The antibody-status breakdown is part of the endpoint question, but the record does not report the category definitions, group sizes, or category-specific endpoint values. It is not possible to assess how stable any subgroup estimate might be.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either meets the stated sPGA response definition or does not. The reported measure is a percentage of participants, and the listed dispersion measure is a 95% confidence interval. The primary analysis set is described as participants with available data. The registry record does not provide the actual response percentage, interval limits, analyzed denominator, or the statistical procedure used to construct the interval.

What does the percentage represent?

A percentage for a binary outcome expresses the share of the analyzed participants who satisfy a prespecified definition. Here, the definition is an sPGA score of 0 or 1 at Week 12. It is not an average sPGA score and it does not describe the distribution across all six scale values. Participants with either qualifying score count toward the response percentage; the endpoint does not distinguish between those two response levels in its responder classification.

The denominator matters. A percentage calculated among participants with available data may differ from a percentage calculated among everyone enrolled if some participants lack Week 12 data. The record identifies the primary analysis set by availability but does not report how many participants had endpoint data, how missing observations were handled, or whether any other analysis populations were used. Thus, the denominator and the implications of missing data cannot be checked from the registry record.

What does a confidence interval add?

General statistical context: a confidence interval gives a range of values compatible with the data and the method used, reflecting sampling uncertainty in an estimate. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. It does not guarantee that the interval contains the true value, and it does not correct bias caused by missing data, selection, measurement, or study design. The registry specifies a 95% confidence interval for the endpoint, but does not report the interval itself or the method used to calculate it. Its width and the precision of the estimate therefore cannot be assessed.

A confidence interval for a single-group percentage would address uncertainty about that group's response proportion. It would not create a comparison with a control group. If subgroup-specific percentages were reported, their intervals would help describe uncertainty within each subgroup; a direct estimate of the difference between groups would be needed to quantify the contrast. Neither subgroup estimates nor a contrast estimate are reported in the registry record.

Why does the design matter for interpretation?

The study is recorded as single-group, open-label, with allocation not applicable. There is no concurrent randomized control group described. General statistical context: randomization can help make treatment groups comparable with respect to both measured and unmeasured characteristics, while masking can reduce some effects of knowledge about treatment assignment on behavior or assessment. In an open-label single-group study, observed outcomes may be affected by expectations, changes over time, selection of participants, and other influences. These considerations do not invalidate a descriptive percentage, but they limit the conclusions that can be drawn about treatment effects.

The primary endpoint is reported by anti-adalimumab antibody status. This is a subgroup analysis question within the treated study population, not an assigned treatment contrast. Interpretation would require the group definitions, subgroup sizes, outcome estimates, and uncertainty measures. The registry record does not report those details. It also does not report whether the subgroup analysis was prespecified or how it was intended to be interpreted.

How should planning calculations be understood?

General statistical context: a sample-size calculation is a planning exercise that depends on assumptions about the effect to detect, variability or event frequency, significance level, allocation, and analysis method. It does not describe an observed outcome or establish that a study had a particular probability of detecting an effect after completion. The planning illustration associated with this analysis is described as using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a stated fraction of an observed effect. It is an illustration based on an observed effect, not the study's own design justification.

That illustration should not be interpreted as the actual design of this trial. The recorded study is single-group, and enrollment is 64; the illustration's assumed equal allocation between two arms does not describe the reported trial design. The registry record does not report the trial's sample-size justification. It also does not report the observed primary endpoint effect needed to assess the planning illustration's assumptions. Any sample sizes in a planning calculation would be prospective illustrations, not observed trial outcomes or observed power.

What statistical results are absent?

The record gives the endpoint definition and the intended confidence-interval measure, but it does not report a p-value, a confidence interval, or a numerical primary outcome. It does not describe an adjustment model, a method for handling repeated observations, or a method for addressing missing data. These methods are not reported in the registry record, and should not be inferred from the endpoint label or the stated design. The registry lists one analysis; this does not establish what procedures were used beyond the information explicitly recorded.

General statistical context: when a study evaluates many outcomes, the chance of at least one chance-positive finding can rise if each is tested independently without adjustment. The record lists 30 outcome measures, but does not report a multiplicity strategy or a hierarchy for interpreting them. Since the primary result itself is not reported, there is no basis for assessing the actual inferential findings or the impact of any multiplicity approach.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Anti-adalimumab Antibody Positive", "Anti-adalimumab Antibody Negative")
n      <- c(40, 20)
events <- c(18, 7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Anti-adalimumab Antibody Positive  40  18  45.0  29.3  61.5  30.7  60.2  30.7  60.3
ARM  Anti-adalimumab Antibody Negative  20  7  35.0  15.4  59.2  18.1  56.7  18.1  57.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 30 outcome measures, including the primary endpoint and secondary sPGA and PASI 50 outcomes. It records one analysis. The number of listed outcomes alone does not reveal how many formal statistical tests were performed, which outcomes were included in the analysis, or how results were prioritized. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a plan for distinguishing confirmatory from exploratory analyses.

General statistical context: evaluating multiple outcomes or subgroups can increase the chance that an apparently notable result occurs by chance. Methods for addressing multiplicity may include adjusting significance thresholds or specifying an ordered testing strategy. Whether either approach was used is not reported in the registry record. With no primary endpoint estimate or secondary outcome results reported, it is not possible to assess how multiplicity affected the study's findings.

For missing data, the primary analysis set is described as participants with available data. The registry record does not report the number of participants with Week 12 data, the reasons for missingness, the handling of missing observations, or sensitivity analyses. It also does not report whether the primary analysis used any imputation or other method. The phrase “with available data” identifies the stated population but does not, by itself, explain how missing outcomes were addressed.

The record does not describe additional analysis populations, such as a protocol-adherent set, or give details on exclusions from the primary analysis. It also does not report whether the endpoint analysis adjusted for other participant characteristics. These details are not reported in the registry record and cannot be inferred from the single-group design or from the endpoint description.

12. Safety Results

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

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: colitis ischaemic (1.6%), diverticulitis (1.6%).

For the Etanercept 50mg BIW/50mg QW group, the registry lists 64 participants at risk for serious adverse events and 2 affected. It lists 64 at risk for other adverse events and 16 affected. These are safety counts for the recorded group; they are not efficacy outcomes and should not be interpreted as evidence about the Week 12 sPGA response.

The serious adverse-event terms listed among the leading terms are colitis ischaemic at 1.6% and diverticulitis at 1.6%. The registry record does not provide further event-level context in the registry record reported, such as timing, outcome, or an assessment of relationship to treatment. The death count is not reported in the registry record.

General statistical context: adverse-event counts describe events or affected participants over the recorded observation period, depending on the registry's reporting convention. A count does not by itself establish that the treatment caused the event. The listed at-risk denominator helps identify the group size associated with the safety figures, but the registry record does not provide a comparator group for contextualizing these counts. The figures should therefore be read as descriptive safety reporting, not as a comparative estimate of risk.

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

The record supports a description of a phase 4, open-label, single-group study evaluating etanercept in participants with moderate to severe plaque psoriasis who had lost a satisfactory response to adalimumab. It specifies a 24-week treatment schedule, a Week 12 primary endpoint, and a response definition based on sPGA scores of 0 or 1. It also records enrollment of 64 and a terminated status.

It does not report the primary endpoint percentage, its 95% confidence interval, or the outcomes by anti-adalimumab antibody status. Therefore, the posted results do not allow readers to determine how often the defined response occurred, how precisely it was estimated, or whether the subgroup results differed. The record's description of what was measured should not be mistaken for a report of what was observed.

Even if a single-group response percentage were available, it would describe outcomes among the participants who received the recorded regimen. Without a concurrent randomized comparator, it would not by itself estimate the difference between etanercept and another treatment or establish that the regimen caused the observed outcomes. Open-label assessment and missing-data handling would also be relevant to interpretation, but the record does not report enough detail to evaluate those issues fully.

The safety figures are likewise descriptive. The record lists serious and other adverse-event counts and two leading serious-event terms, but does not provide a comparator or the additional context needed to attribute events to treatment. The reason for study termination is not reported in the registry record, so termination should not be taken as evidence for or against any particular outcome.

In practical statistical terms, the record defines a study question and records basic design and safety information, but leaves the primary efficacy result unavailable. No conclusion about the magnitude, precision, or comparative effect of the response can be drawn from the registry record as reported.

14. Why This Trial Matters Statistically

This study illustrates why design information and outcome information need to be read separately. The registry record identifies a specific population, regimen, endpoint, assessment time, and analysis population. Those details make the research question understandable. But without the endpoint estimate and its uncertainty, the central statistical result remains unknown. An endpoint definition is not a substitute for the reported value.

The single-group, open-label design also clarifies the scope of a possible result. A response percentage could describe what occurred among participants receiving etanercept under the study schedule. It would not establish how outcomes compare with an alternative, because no control group is described. This is an important distinction when translating a descriptive outcome into a claim about treatment effects. The distinction remains even when a result is precisely estimated: precision does not remove the limitations of the design.

The endpoint's breakdown by anti-adalimumab antibody status highlights another statistical issue. Subgroups can be clinically and scientifically relevant, but subgroup estimates need their own denominators and uncertainty measures. A difference between subgroup percentages would be descriptive unless the analysis and design support a stronger interpretation. Here the subgroup results and group sizes are not reported.

The record also demonstrates the importance of transparent reporting about missing data and multiplicity. It identifies the primary analysis set as participants with available data and lists 30 outcome measures, yet does not report the missing-data approach or a multiplicity strategy. Those omissions make it harder to assess how the results would be interpreted even if outcome estimates were available.

Finally, the reported safety counts answer a different question from the primary efficacy endpoint. Keeping those outcomes distinct prevents safety reporting from being treated as a proxy for response. Together, these features make the record useful for understanding the planned question and the limits of the reported evidence, while leaving the primary efficacy findings unassessable.

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 most consequential limitation for statistical interpretation is that the primary endpoint result is not reported in the registry record. There is no Week 12 response percentage, 95% confidence interval, or antibody-status-specific result. The number of participants contributing data to that endpoint is also not reported. As a result, the magnitude and precision of the primary outcome cannot be assessed.

The study is recorded as single-group and open-label, with no randomized comparator described. Any reported outcome would therefore be descriptive of the treated group rather than a direct estimate from a controlled comparison. The design cannot separate treatment-associated change from other influences using a concurrent control contrast. Open-label status may also matter when outcomes depend on assessment, but the record does not report additional procedures that might address that concern.

The record does not report the reason for termination. It also does not explain the missing primary result, report the number of participants with available Week 12 data, or describe how missing observations were handled. The primary analysis population is defined only as participants with available data. These gaps prevent assessment of whether the analyzed participants differed from those without endpoint data.

Further limitations include the absence of reported subgroup sizes and antibody-status-specific estimates, no described multiplicity strategy despite 30 listed outcome measures, and no reported sample-size justification. The planning illustration is not a substitute for the study's design rationale and does not establish observed power. The record also does not report details of the confidence-interval method or other statistical procedures. These limitations restrict interpretation to the design and outcome definitions that are explicitly recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Etanercept Treatment in Patients With Moderate to Severe Plaque Psoriasis Who Lost Response to Adalimumab — NCT01543204.
• Registry record last updated 2017-12-29; status last verified 2017-12.
• Results first posted 2016-06-27.
• 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

This phase 4 study evaluated etanercept in participants with moderate to severe plaque psoriasis who had lost a satisfactory response to adalimumab. It was open-label and single-group, with enrollment of 64, and is recorded as terminated. The regimen was etanercept 50 mg subcutaneously twice weekly for 12 weeks, followed by 50 mg once weekly for an additional 12 weeks.

The primary endpoint was the percentage with an sPGA score of 0 or 1 at Week 12, reported by anti-adalimumab antibody status. The primary analysis set was participants with available data, and the specified dispersion measure was a 95% confidence interval. The registry record does not report the endpoint result, the confidence interval, subgroup results, missing-data methods, or the reason for termination.

Safety reporting lists 2 affected participants for serious adverse events and 16 for other adverse events, each among 64 at risk. The leading serious-event terms listed are colitis ischaemic and diverticulitis, each at 1.6%. These safety figures are descriptive and do not replace the unreported primary efficacy result.