Acitretin and Etanercept in Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acitretin and Etanercept in Psoriasis (NCT00156247), a na phase 2 study. The primary outcome is Percent of Patients Achieving PASI 75 at 6 Months After the Addition of Acitretin Therapy.

2. Clinical Question

The registry describes the study as a pilot, single-arm phase 2 study. Its stated purpose was to assess whether the combination was more effective than etanercept alone in clearing psoriasis plaques in adults. That stated purpose is a question, not evidence that the study can estimate a comparative treatment effect. Without an etanercept-only group assessed over the same period, changes after adding acitretin cannot be separated from changes that might have occurred with continued etanercept, the course of disease, or other influences.

The primary outcome is defined at a particular follow-up time, 6 months after acitretin therapy was added. Two secondary outcomes are also named: PASI 50 and a Physician Global Assessment (PGA) rating of clear or almost clear at that time. The registry record does not report results for the primary or secondary outcomes. Accordingly, it does not establish how many participants met any of these response definitions.

3. Trial Design

This is a phase 2, single-group, open-label pilot study of adding acitretin to etanercept therapy. The registry lists enrollment as 10, allocation as NA, masking as none, and the model as single group. It identifies the University of Medicine and Dentistry of New Jersey as sponsor. The recorded start is 2005-09, primary completion is 2009-03, and status is completed.

The study population is described in the official title as patients with moderate to severe psoriasis who fail to respond to etanercept monotherapy. The named intervention is acitretin, and the arm description is etanercept with acitretin. The study is open-label, so treatment masking is not part of the design as recorded. The registry record does not provide further details about how response to etanercept was established, how participants were selected, or how treatment was administered.

A single-group design can describe outcomes among participants receiving the combination, but it does not create a concurrent estimate of what would have happened to comparable participants receiving etanercept alone. The brief summary frames a comparison with etanercept alone, while the recorded design has no control arm. Thus, even if a response result were available, it would describe outcomes within the treated group rather than a randomized or otherwise like-for-like contrast.

The registry identifies three outcome measures, including the primary PASI 75 outcome and the two secondary outcomes. It lists no analysis records. Details of the analysis population, statistical model, handling of missing outcomes, and any adjustment for multiple outcomes are not reported in the registry record. The designation completed describes the study's status; it does not by itself mean that outcome findings or a statistical analysis are available in the 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

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 Percent of Patients Achieving PASI 75 at 6 Months After the Addition of Acitretin Therapy, measured over 6 months.

The primary endpoint is the percent of patients achieving PASI 75 at 6 months after acitretin was added to etanercept therapy. A participant meets the response definition by having at least a 75% decrease from baseline in the Psoriasis Area and Severity Index (PASI). The index combines assessments of erythema, desquamation, infiltration, and affected body surface area. The described scale ranges from 0 to 72, with 0 indicating no psoriasis and 72 indicating severe disease.

A threshold endpoint translates change on a disease-severity scale into a clinically interpretable responder category: participants either meet or do not meet the stated response criterion. PASI is used in this outcome to capture several features of psoriasis severity rather than relying on a single feature. The 6-month time point specifies when response is assessed, which is important because outcomes can depend on the follow-up time used.

As a general statistical point, a responder percentage is most informative when its numerator, denominator, and uncertainty are reported together. A percentage alone can conceal how much information supports it, especially in a small study. Here, the registry record gives the endpoint definition but does not report the observed percentage, the count of responders, a confidence interval, or an analysis. The endpoint therefore cannot be interpreted as evidence of the magnitude or precision of response in this study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a phase 2, open-label, single-group study and names a binary responder outcome expressed as a percentage. It does not report the statistical methods used to analyze that endpoint, and it lists no analysis records. The explanations below describe general statistical principles relevant to this type of study; they should not be read as a claim that a particular method was used in this trial.

What does a responder percentage represent?

A responder percentage is the proportion of an analysis group meeting a prespecified outcome definition. For this study, the definition is achieving at least a 75% decrease from baseline in PASI at 6 months. To interpret a reported percentage, readers need to know both how many participants met the criterion and how many were included in its denominator. The denominator can depend on whether the analysis includes all enrolled participants, only participants with a follow-up assessment, or another defined population. The registry record does not report the primary endpoint's numerator, denominator, or analysis population.

Responder outcomes are straightforward to communicate, but turning a continuous scale into a category discards information about the size of changes within each category. Participants just above and well above the response threshold are counted alike, as are participants just below the threshold and those with little change. For that reason, reporting the responder outcome alongside the underlying scale or other relevant summaries can help readers understand the pattern. Such additional primary endpoint results are not reported in the registry record.

Why does uncertainty matter?

A point estimate, such as a percentage, is an estimate based on the observed participants. A confidence interval is a range calculated by a statistical procedure to express uncertainty around an estimate. It reflects how compatible a range of values is with the data under the assumptions of that procedure. It does not guarantee that the true value lies in the interval, nor does it address biases caused by study design or missing data. No confidence interval for PASI 75 is reported in the registry record.

Small studies generally provide less precise estimates than larger studies when other features are similar. This is a general principle, not a calculated precision statement for this trial. The enrollment entry is 10, but the record does not give the primary outcome denominator, outcome count, or uncertainty estimate. A precise assessment of the endpoint cannot be reconstructed from the enrollment entry alone.

What can a single-group design estimate?

A single-group study can describe outcomes observed after participants receive an intervention. In this case, an outcome estimate would concern the group receiving etanercept with acitretin. A comparative treatment effect, however, requires a basis for estimating what would have happened under a different treatment strategy. A concurrent control group can provide that basis when the groups are suitably comparable. The registry records no such group and identifies the design as single-group.

As a general matter, comparing participants with their own baseline can describe change, but it does not remove all alternative explanations for that change. Baseline and follow-up measurements occur at different times, and changes over time may reflect factors other than the added treatment. Without a control group, an observed improvement cannot be attributed uniquely to the addition of acitretin. In this study, the primary endpoint description refers to change from baseline, but the record does not report the observed change or the analysis used.

What is the role of masking?

Masking is intended to reduce the influence of knowledge about treatment assignment on care, participant reports, or outcome assessment. The registry records masking as none and describes the treatment as open-label. As a general principle, lack of masking can matter more when outcomes depend on judgment or reporting than when they are measured by an objective procedure. PASI includes assessments of visible signs and affected body surface area, while PGA is a global assessment. This makes consistent assessment procedures relevant, but the registry record does not describe assessor training, independent review, or other safeguards.

How should planning calculations be read?

The registry record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. For outcomes other than time-to-event outcomes, such illustrations are expressed as participants per arm; time-to-event illustrations are expressed as a total number of events. The record does not give the observed effect or numerical planning results in the information available for this interpretation.

Such calculations are planning illustrations, not observed power. A sample-size calculation asks what sample size would be needed under specified assumptions to detect a chosen effect with a chosen operating characteristic. It does not establish that a study with a particular enrollment had a specific probability of finding an effect, and it does not show that an effect was observed. The illustrations described in the registry assumptions also use a two-arm equal-allocation framework, whereas this study's recorded design is single-group. They should not be treated as evidence that the trial was designed or analyzed as a two-arm comparison.

What can a p-value establish?

As a general explanation, a p-value measures how surprising data at least as incompatible with a specified null model would be if that model and the statistical assumptions were true. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. A p-value also does not correct for a weak comparison or an unmasked design. No p-value or analysis result for the primary outcome is reported in the registry record.

Overall, the record makes the endpoint and design identifiable but does not provide the numerical outcome data or the analysis details needed to evaluate effect size and uncertainty. General statistical concepts can clarify what those missing elements would mean, but they cannot substitute for the unreported analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies PASI 75 as the primary outcome and names PASI 50 and PGA clear or almost clear as secondary outcomes, all assessed at 6 months after acitretin was added. It lists three outcome measures. The results for these outcomes and the analysis records are not reported in the registry record. The record does not specify whether the outcomes were analyzed as originally planned, whether any additional outcomes were examined, or how the results were handled statistically.

Multiplicity arises when several outcomes, time points, subgroups, or analyses are assessed. As a general principle, the more statistical tests considered, the greater the chance that at least one result may appear notable by chance if no adjustment or prespecified hierarchy is used. Methods for addressing this include defining a primary outcome in advance, controlling an overall error rate, or treating secondary outcomes as exploratory. The record identifies a primary outcome, but multiplicity procedures or a testing hierarchy beyond that designation are not reported in the registry record.

Missing outcome data can affect both the estimated response and its uncertainty. The interpretation depends on how much data are missing, why they are missing, and how the analysis handles participants without an assessment. The registry record does not report missingness for PASI 75, the reasons for any missing assessments, or an imputation or sensitivity-analysis approach. It also does not define the primary analysis population or explain whether participants without a 6-month result were included in a particular way.

The enrollment entry is 10, while the safety group lists 9 at risk. The record does not explain that difference, and the safety denominator should not be assumed to be the primary endpoint denominator. Neither entry establishes the number with evaluable PASI data. Consequently, the response rate and the influence of missing outcome data cannot be assessed from the registry record.

11. 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 non-serious adverse event terms

The registry lists an adverse-event group titled Etanercept With Acitretin. In that group, 9 participants are recorded as at risk for serious adverse events, and 0 are recorded as affected. For other adverse events, 9 are recorded as at risk and 2 as affected. These entries describe the counts in the registry's safety categories; they do not provide event-level descriptions in the information.

The deaths entry is null. This means deaths are not reported in the registry record; it should not be read as a reported count of zero. The record also lists no top serious-event terms, which does not supply further detail about the safety observations or explain how events were collected and classified.

As a general statistical principle, safety counts need denominators and clear definitions. The at-risk group size indicates the denominator recorded for each category, but the record does not explain why it is 9 when overall enrollment is listed as 10. A small number of reported events cannot rule out uncommon harms, and these counts should not be interpreted as a complete assessment of safety. They also do not establish a comparison with etanercept alone, because there is no concurrent control group in the recorded design.

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

The registry record establishes that the study was designed to examine acitretin added to etanercept in people described as having moderate to severe psoriasis who did not respond to etanercept monotherapy. It specifies PASI 75 at 6 months as the primary endpoint and gives the response definition. It also records a completed, phase 2, open-label, single-group study with enrollment of 10.

Those details describe what was studied, not what the primary outcome showed. The registry record does not report the PASI 75 result, its denominator, a confidence interval, or an analysis. The secondary outcome results are not reported either. Therefore, the record cannot establish the proportion achieving the defined response, how precise an estimate would be, or whether outcomes differed across response criteria.

The study's stated question asks whether the combination is more effective than etanercept alone. The recorded single-group design does not include an etanercept-only comparator. Even if within-group response results were available, they would not by themselves estimate a comparative effect. General statistical reasoning cautions that changes from baseline can have explanations other than the added treatment, and the absence of masking can be relevant to assessment. These are limitations of inference, not evidence for or against benefit.

The safety entries report 0 serious adverse events among 9 recorded at risk and 2 other adverse events among 9 recorded at risk. The deaths field is not reported in the registry record. These entries are limited safety counts, not a comprehensive estimate of risk or a controlled comparison.

Accordingly, the record supports a careful account of the trial question, design, endpoint definitions, and limited safety reporting. It does not support a numerical statement about primary efficacy, a conclusion about comparative effectiveness, or a conclusion that the intervention is effective or ineffective. Those questions require outcome and analysis information not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why the registered question and the design must be read together. The brief summary asks whether acitretin plus etanercept is more effective than etanercept alone, but the study is recorded as single-group, with no concurrent etanercept-only control. The intended comparison and the comparison actually supported by the design are therefore not the same. This distinction is important when interpreting any within-group change.

The registry also shows why endpoint definitions alone are not enough to interpret a trial. PASI 75 is described clearly as at least a 75% improvement from baseline at 6 months, and PASI itself combines several features of psoriasis severity. Yet without the responder count, denominator, estimate, and uncertainty, the definition cannot tell readers how participants fared. A well-defined endpoint is necessary for interpretation, but it cannot replace the results.

The record highlights the need to consider analysis populations and missing data alongside enrollment. Enrollment is listed as 10, whereas the safety denominator is 9. Because the record does not explain the difference, it cannot be assumed that either figure is the denominator for the primary endpoint. Clear accounting of participants at each stage and for each outcome is essential to understanding the evidence.

Finally, this record demonstrates the limits of registry entries when results and analysis details are absent. The study is marked completed, and three outcome measures are identified, but no analysis records or outcome findings are listed. Completion status and outcome specification should not be mistaken for a statistical result. For biostatisticians and clinical researchers, the key lesson is to distinguish study intent, design capacity, and reported evidence before making claims about effect or precision.

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.

Several limitations are specific to this study as recorded. It is a pilot, single-group study, not a randomized comparison. The registry's stated interest in whether adding acitretin is more effective than etanercept alone cannot be answered directly by the design described, because an etanercept-only control group is not listed. No adjustment or design feature that would create a like-for-like comparison is reported in the registry record.

The study is open-label, with masking recorded as none. The record does not describe whether outcome assessors were independent or whether standardized assessment procedures were used. This matters to interpretation because the primary PASI outcome includes assessments of signs and affected body surface area, and one secondary measure is a global assessment. The implications cannot be quantified from the record.

The primary outcome is defined, but its observed result and analysis are not reported. The record also does not provide the responder count, endpoint denominator, confidence interval, p-value, analysis population, or handling of missing outcome data. It therefore does not allow assessment of the primary estimate's precision or robustness. The secondary outcomes are named but their results are also not reported.

Enrollment is listed as 10, while the adverse-event group records 9 at risk. The record does not explain the discrepancy or identify how participants contributed to each outcome. Deaths are not reported in the registry record. Safety reporting is thus limited to the listed event counts and cannot establish comparative safety.

Finally, the record does not report a statistical analysis plan, multiplicity handling, or a sample-size justification for this single-group design. Planning assumptions describe a two-arm equal-allocation illustration, but numerical planning results and the underlying observed effect are not reported in the registry record. These gaps limit the conclusions that can be drawn from the registry record, without implying that unreported procedures or findings did not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Acitretin and Etanercept in Psoriasis — NCT00156247.
• Registry record last updated 2015-02-16; status last verified 2015-02.
• Results first posted 2015-02-16.
• 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.

18. Record Summary

NCT00156247 is a completed phase 2 pilot study sponsored by the University of Medicine and Dentistry of New Jersey. It is recorded as an open-label, single-group study with enrollment of 10. The recorded start is 2005-09 and primary completion is 2009-03.

The study examines acitretin added to etanercept therapy for adults with moderate to severe psoriasis who fail to respond to etanercept monotherapy. PASI 75 at 6 months is the primary outcome; PASI 50 and PGA clear or almost clear at 6 months are secondary outcomes. Outcome results and analysis records are not reported in the registry record.

The safety group records 0 serious adverse events among 9 at risk and 2 other adverse events among 9 at risk. Deaths are not reported in the registry record. The single-group design does not provide a concurrent etanercept-only comparison, so the record does not establish a comparative treatment effect.