Study to Evaluate the Efficacy of Etanercept Treatment in Adults Who Failed Therapy With Apremilast: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Efficacy of Etanercept Treatment in Adults Who Failed Therapy With Apremilast (NCT02749370), a na phase 4 study. The primary outcome is Percentage of Participants With a PASI 75 Response at Week 12.

2. Clinical Question

The question is about change in psoriasis severity during treatment in a particular population: adults with moderate to severe plaque psoriasis who had failed apremilast therapy. It is not a randomized comparison of etanercept against another treatment, placebo, or usual care. Without a comparator group, the study can describe the outcome recorded for participants receiving etanercept, but it cannot by itself distinguish treatment-associated change from other influences on change over time.

The primary outcome is a threshold response rather than a comparison of average PASI scores. Participants count as responders if their PASI score improves by at least 75% from baseline. The registry record also names secondary outcomes concerning other PASI response thresholds, percent change in PASI, and static Physician Global Assessment measures. Their results are not reported in the registry record.

3. Trial Design

This is a phase 4, open-label, single-group study of etanercept in adults with moderate to severe plaque psoriasis who had failed therapy with apremilast. The registry record lists Amgen as sponsor, an enrollment of 80, and a completed status. The recorded study start is 2016-05-18, and the primary completion date is 2017-08-14.

All participants were assigned to the etanercept intervention; no separate comparator arm is described. Allocation is listed as not applicable, and masking is listed as none. Consequently, the study design does not provide a blinded, randomized comparison between etanercept and another treatment. Open-label treatment means the study is not described as masking participants or study personnel to treatment assignment.

The recorded regimen was 50 mg etanercept subcutaneously twice weekly for 12 weeks, followed by 50 mg once weekly for an additional 12 weeks. The primary outcome was the percentage of participants with a PASI 75 response at week 12. The named secondary outcomes include PASI 50 and PASI 90 response, percent change in PASI, and several sPGA outcomes assessed at visits.

The 80 participants listed as enrolled should not automatically be treated as the denominator for every outcome. The primary-outcome population is defined by receipt of at least one dose and availability of at least one post-baseline PASI value. The number meeting that definition, the number with observed week-12 measurements, and the number included in the reported primary analysis are not reported in the registry record. The record also does not describe a separate control group or a statistical comparison against one.

Study status and dates describe the registry record, not the completeness of every outcome result. Although the study is marked completed, the primary outcome estimate and its confidence interval are not reported in the registry record. The planned sample-size justification and any additional protocol details are also 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who received at least 1 dose of etanercept during the study and with at least 1 post-baseline PASI value. Last observation carried forward (LOCF) imputation was used for participants with missing data at week 12.

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 a PASI 75 Response at Week 12, measured over Baseline and week 12.

The primary endpoint is the percentage of participants with a PASI 75 response at week 12. A response means at least a 75% improvement, or reduction, from baseline in PASI score. PASI combines ratings of redness, thickness, and scaliness of psoriasis lesions with the area of involvement across the head and neck, trunk, upper extremities, and lower extremities. The score ranges from 0 to 72; higher scores indicate greater severity and/or more extensive psoriasis.

A threshold response expresses whether each participant crossed a defined improvement level. This can be easier to interpret than a score change alone, but it does not show how far beyond the threshold a responder improved, nor does it describe the distribution of changes among all participants. A percentage response also depends on the baseline score and on how missing observations are handled.

As a general statistical point, a confidence interval communicates uncertainty around an estimated response percentage. A narrower interval indicates greater precision under the analysis assumptions; a wider interval indicates more uncertainty. The registry record specifies a 95% confidence interval for this endpoint, but does not report the response estimate or the interval limits. The endpoint's result and its precision therefore cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods described in the registry record are limited. They identify an open-label, single-group study, define the primary endpoint and its analysis population, specify a 95% confidence interval, and state that last observation carried forward was used for missing week-12 data. The statistical model, exact confidence-interval method, and other details of the analysis are not reported in the registry record. The explanations below distinguish those recorded details from general statistical concepts.

What does a single-group design estimate?

In general, a single-group study can estimate an outcome among participants receiving the studied intervention. For this trial, the stated primary outcome is the percentage meeting the PASI 75 threshold at week 12. Because no comparator group is described, this percentage would be a description of the study group under the stated treatment and analysis procedures, not a randomized estimate of the difference between treatments.

Randomized comparisons are designed to make treatment groups comparable on average, subject to the study's conduct and analysis. A single-group design cannot use a concurrent randomized group to separate changes associated with treatment from changes that might have occurred for other reasons. This is a general limitation of the design, not evidence that any particular alternative explanation occurred in this study.

What does a 95% confidence interval communicate?

In general, a confidence interval expresses uncertainty around an estimate under the method's assumptions. For a response percentage, the interval would describe a range of values compatible with the observed data and the specified procedure. Its width reflects precision: less information or greater variability will generally yield less precise estimates. A confidence interval does not establish that the treatment caused the outcome, and it does not remedy the lack of a comparator group.

The registry record specifies a 95% confidence interval for the primary outcome but does not give its limits or the response estimate. The procedure used to calculate it is not reported in the registry record. The interval's precision, coverage of a particular benchmark, and compatibility with any alternative value therefore cannot be evaluated from the registry record.

How should the PASI 75 threshold be understood?

The endpoint classifies each participant according to whether PASI improved by at least 75% from baseline at week 12. PASI itself combines lesion redness, thickness, and scaliness with the affected area across specified body regions. In general, converting a continuous score change into a threshold response makes the result interpretable as a proportion meeting a defined criterion. However, thresholding discards detail: participants just meeting the criterion and those improving substantially beyond it are both counted as responders. Those who do not reach the threshold may still have experienced a change, but the binary outcome does not describe its size.

The registry also lists secondary outcomes based on other PASI thresholds, PASI percent change, and sPGA ratings. These endpoints capture different aspects or thresholds of response. The results for those measures are not reported in the registry record, and their presence in the outcome list should not be read as a result.

What is last observation carried forward?

Last observation carried forward, or LOCF, is an imputation approach: when a week-12 value is missing, an earlier observed value is used in its place for the analysis. In general, this creates a complete value for the planned time point, but it relies on an assumption that carrying the earlier measurement forward is a reasonable representation of the missing week-12 measurement. If the outcome would have changed after the last observation, carrying that observation forward may misrepresent the later status.

The registry record states that LOCF was used for participants with missing data at week 12. It does not report how many values were missing, the timing of the last observations carried forward, reasons for missingness, or sensitivity analyses using other approaches. Without those details, the influence of imputation on the estimate cannot be assessed.

What does the analysis population mean?

The stated primary population includes participants who received at least one etanercept dose during the study and had at least one post-baseline PASI value. This is a defined analysis set, rather than an assurance that every enrolled participant was analyzed. In general, eligibility for an analysis population can affect the denominator and the interpretation of its estimate. The registry record does not report the count in this population, the number analyzed at week 12, or participant-level disposition.

The record lists an enrollment of 80, but that figure alone does not establish the denominator for the primary outcome. The number of outcome measures listed in the registry is not a substitute for a numerical endpoint result or an analysis sample size.

What statistical plan details are absent?

The statistical analysis plan, sample-size justification, model specification, confidence-interval procedure, interim analyses, and multiplicity strategy are not reported in the registry record. No p-values or analysis results are listed. As a general matter, these details help readers assess how estimates were chosen, how uncertainty was quantified, and whether conclusions account for multiple outcomes or analyses. Their absence from the registry record means those aspects cannot be evaluated from the posted information.

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("Etanercept")
n      <- c(77)
events <- c(32)
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  Etanercept  77  32  41.6  30.4  53.4  31.2  52.7  31.2  52.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and multiple secondary outcomes. The secondary outcomes cover PASI 50 and PASI 90 response, percent change in PASI, sPGA categories at visits, and change in sPGA from baseline. Assessing several outcomes can raise a multiplicity question: in general, the more statistical tests or claims considered, the greater the chance of at least one apparently notable result arising by chance if no adjustment is used.

The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a statistical analysis plan explaining how multiple endpoints were handled. It also does not report p-values or numerical results for the primary or secondary outcomes. The presence of several registered outcome definitions does not indicate that statistical significance was tested or established.

For the primary endpoint, the record states that LOCF was used for participants with missing week-12 data. It does not report the number of missing values, reasons for missingness, the number imputed, or any sensitivity analysis. In general, missing-data methods require assumptions about the unobserved values; LOCF carries an earlier value forward, which may not represent the participant's status at the later assessment if the outcome changed. The registry record does not provide enough detail to evaluate how sensitive the primary result might be to those assumptions.

The primary-outcome population is described as participants who received at least one dose and had at least one post-baseline PASI value. The count meeting that definition and the number included in the endpoint analysis are not reported in the registry record. The listed enrollment of 80 should therefore not be assumed to be the primary analysis denominator. Other details relevant to missing-data assessment, including participant flow and analysis exclusions, are not reported in the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: drug eruption (2.5%), injection site reaction (1.2%).

The registry record lists 80 participants at risk in the etanercept group, 2 participants with a serious adverse event, 18 with other adverse events, and 0 deaths. These are safety counts recorded for the single study group; they are not a comparison with a control group. The record also lists Drug eruption at 2.5% and Injection site reaction at 1.2% among the top serious terms.

Counts of participants and percentages attached to event terms describe different summaries. The listed term percentages should not be added together or treated as a total adverse-event percentage. The registry record does not provide additional detail about event timing, severity beyond the serious classification, relatedness assessment, recurrence, or the method used to derive the term percentages. It also does not report a comparative safety estimate.

In general, safety counts in a study of this design describe events recorded in the treated group over the period captured by the study. They do not, by themselves, establish whether an event was caused by treatment or how its frequency compares with another treatment. The absence of a control group limits comparative interpretation.

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

The registry record describes a study intended to evaluate etanercept in adults with moderate to severe plaque psoriasis who had failed therapy with apremilast. It specifies an open-label, single-group design and identifies PASI 75 response at week 12 as the primary outcome. The treatment regimen and the primary analysis population are also stated.

However, the primary response percentage and its 95% confidence interval are not reported in the registry record. Without those values, the magnitude and precision of the primary outcome cannot be described. The registry record also does not report the results for the named secondary outcomes. Study completion and enrollment do not supply the missing endpoint estimates.

Even if an outcome estimate were available, a single-group study would describe the observed result among participants receiving etanercept; it would not provide a randomized comparison against another treatment. In general, before-and-after changes can reflect influences beyond the intervention, and a concurrent comparator helps address that interpretive problem. No such group is described in this study.

The threshold nature of PASI 75 also matters. It identifies whether participants reached a defined degree of improvement, rather than showing the full pattern of PASI change. A response proportion does not indicate how much individual responders improved beyond the threshold, or how much nonresponders changed. The LOCF approach to missing week-12 observations is recorded, but the amount and pattern of missing data are not reported, so its effect on the estimate cannot be judged.

The safety record lists adverse-event counts and selected serious-event terms, but there is no control group for comparison. Those data describe events recorded in the study and do not alone establish causation or comparative risk. Overall, the registry record supports a description of the research question and methods, but it does not provide the numerical efficacy results needed to assess the primary endpoint.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how the design and endpoint determine what an estimate can mean. The stated question focuses on a defined response threshold, PASI 75 at week 12, in adults with moderate to severe plaque psoriasis who had failed apremilast therapy. The population and endpoint are specific, which clarifies the intended scope of the result.

At the same time, the single-group design sets a clear boundary on interpretation. It can describe the outcome among participants treated with etanercept, but it does not create a randomized contrast against another treatment. This distinction is fundamental: an outcome observed over time is not the same statistical quantity as a difference between treatment groups. A result should be interpreted in light of the design that generated it.

The endpoint also illustrates the trade-off involved in threshold outcomes. A PASI 75 response percentage is readily expressed as the proportion meeting a defined improvement criterion. But reducing score changes to responder status loses information about the degree of change among responders and nonresponders. Other listed outcomes, including PASI percent change and sPGA measures, could describe different dimensions of response, but their results are not reported in the registry record.

Finally, the record specifies an approach to missing week-12 measurements, LOCF, while omitting the number and pattern of missing observations and any sensitivity analyses. This highlights why interpretation depends not only on an endpoint definition but also on the analysis population, missing-data assumptions, and reporting of uncertainty. Here, the primary estimate and its confidence interval are not reported, so the intended statistical question is identifiable but its observed answer cannot be evaluated from the registry record.

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 principal limitation for interpreting the posted results is that the registry record does not report the primary PASI 75 response estimate or its 95% confidence interval. It also does not report numerical results for the secondary outcomes. As a result, the magnitude, precision, and pattern of outcomes cannot be assessed from the registry record.

The study is described as open label and single group, with no separate comparator arm. This precludes a randomized between-group comparison and limits causal interpretation of change over time. The registry record does not describe blinding, allocation to competing treatments, or a control condition; allocation is listed as not applicable.

The endpoint analysis population requires at least one etanercept dose and at least one post-baseline PASI value. The number of participants meeting this definition and the number included in the primary analysis are not reported. Although enrollment is listed as 80, the analysis denominator cannot be inferred from enrollment alone. Participant flow and reasons for missing measurements are also not reported in the registry record.

LOCF is specified for missing week-12 PASI data, but the amount of imputation, timing of the carried-forward observations, and any sensitivity analyses are not reported. The statistical analysis plan, confidence-interval calculation method, multiplicity strategy, sample-size justification, and interim analyses are not reported in the registry record. These omissions limit assessment of the assumptions and procedures behind any estimates. The record's completed status does not resolve these reporting limitations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Efficacy of Etanercept Treatment in Adults Who Failed Therapy With Apremilast — NCT02749370.
• Registry record last updated 2020-05-13; status last verified 2020-05.
• Results first posted 2018-08-27.
• 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

The registry record describes NCT02749370, a completed phase 4, open-label, single-group study sponsored by Amgen. It lists an enrollment of 80 and evaluates etanercept in adults with moderate to severe plaque psoriasis who had failed therapy with apremilast. The regimen was 50 mg subcutaneously twice weekly for 12 weeks, followed by 50 mg once weekly for an additional 12 weeks.

The primary outcome was the percentage of participants with a PASI 75 response at week 12, defined as at least a 75% improvement from baseline. The stated analysis population included participants who received at least one dose and had at least one post-baseline PASI value; LOCF was used for missing week-12 data. The primary estimate and its 95% confidence interval are not reported in the registry record. The record lists 2 participants with serious adverse events, 18 with other adverse events, and 0 deaths, without a comparator group.