Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis (NCT05125679), a na phase 4 study. The primary outcome is Change From Baseline in Coronary Flow Reserve (CFR) at Week 32.

2. Clinical Question

The study also listed changes in CFR at Week 16, global longitudinal strain, and carotid-femoral pulse wave velocity among its secondary outcomes. These are cardiovascular surrogate measures; the registry record does not describe clinical cardiovascular events as the primary endpoint. Because the design has no concurrent comparator, any observed baseline-to-follow-up change would describe change over time among the assessed participants. By itself, such a change would not separate a treatment effect from other explanations, including natural variation or measurement variability.

3. Trial Design

This was a Phase 4, interventional, single-group, open-label study of guselkumab in participants with moderate to severe plaque psoriasis. The registry lists enrollment as 15 and the study status as terminated. The record gives a study start date of 2021-11-23 and a primary completion date of 2023-07-28. The reason for termination is not reported in the registry record.

All participants were assigned to the guselkumab intervention; there was no randomized allocation or separate control arm. The specified regimen was 100 mg by subcutaneous injection at Weeks 0, 4, 12, 20 and 28. Masking was listed as none. The registry identifies Janssen-Cilag Ltd. as the sponsor.

The primary outcome was change from baseline in CFR at Week 32. The record describes CFR measurement by transthoracic Doppler echocardiography, using blood-flow measurements at rest and during pharmacological stress. Baseline was defined as the last non-missing measurement before or on the day of the first guselkumab dose. The primary outcome population was described as treated participants evaluable for the measure, with CFR from 2 to 3.5 at screening and baseline.

The registry lists 17 outcome measures, including secondary assessments of CFR, absolute global longitudinal strain, and carotid-femoral pulse wave velocity. It records 0 analyses. Numerical primary outcome results and the analysis methods used to estimate them are not reported in the registry record. The record also does not report a statistical analysis plan or the reason the study was terminated.

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: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2 and \<=3.5 at screening visit 2 (2 to 4 weeks prior to Week 0) and baseline (Week 0).

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Coronary Flow Reserve (CFR) at Week 32, measured over Baseline (Week 0) and Week 32.

The primary endpoint was change from baseline in coronary flow reserve at Week 32, expressed as a ratio. CFR compares coronary blood flow during stress, when the coronary arteries are maximally dilated, with blood flow at rest. The registry describes CFR as an indicator of the ability of coronary blood flow to increase in response to metabolic demand.

For measurement, the study recorded Doppler signals from the distal left anterior descending artery and then administered adenosine as a coronary vasodilator. Doppler signals were recorded during the infusion. The baseline value was the last non-missing measurement before or on the day of the first dose. The endpoint thus focuses on the difference between a participant’s baseline CFR and the Week 32 measurement.

As a general statistical concept, a surrogate marker is a measured indicator used to study a biological process related to health, rather than a direct count of clinical events. CFR can describe coronary flow response under the measurement conditions in the protocol, but a change in a surrogate measure is not itself evidence about whether clinical cardiovascular events changed. Interpreting a mean change also requires its numerical estimate and information about variability or uncertainty. Those primary outcome results are not reported in the registry record, so the magnitude and precision of the change cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

The primary measure is continuous and is summarized as a mean. A change-from-baseline analysis focuses on the difference between a participant’s follow-up measure and baseline measure, then summarizes those changes across the participants included in the analysis. This approach keeps the question tied to change within the measured group rather than comparing separate treatment arms.

As a general statistical concept, the mean is sensitive to the values included in the analysis. The analysis population and the availability of measurements can therefore affect the estimate. The registry describes the primary population as treated participants evaluable for CFR and meeting the stated CFR range at screening and baseline. It does not report the number analyzed or the numerical mean change.

What does the standard deviation add?

The registry identifies standard deviation as the measure of dispersion for the primary outcome. As a general concept, standard deviation describes how far individual observations tend to vary around the mean. It is not the same as the uncertainty around the estimated mean: uncertainty also depends on how much information contributes to the estimate and on the analysis approach. Since the registry record does not report the standard deviation or a confidence interval for the primary change, the spread and precision of the result cannot be evaluated.

Why does the design affect interpretation?

This is a single-group, open-label study, with no concurrent comparator. As a general statistical principle, a within-group change can describe the observed pattern over time but cannot by itself distinguish an intervention effect from time trends, measurement variation, or other influences. A randomized comparator can support a direct between-group contrast; this study’s registry design does not include one. Open-label status also means masking was not used, although the record does not report whether or how that could have affected outcome measurement.

The endpoint itself uses an objective physiological measure, but the registry’s method description does not eliminate the need to examine the actual data, completeness of measurements, and analysis procedures. Those result-level details are not reported in the registry record.

What does a confidence interval communicate?

As a general statistical concept, a confidence interval expresses uncertainty around an estimated quantity. A relatively narrow interval indicates greater precision under the chosen method, while a wider interval indicates less precision. A confidence interval is not a guarantee that the true value lies within the reported range, and it does not by itself establish clinical importance. The registry record does not report a confidence interval for the primary outcome, so its precision cannot be judged.

How should the planning illustrations be read?

Sample-size calculations based on an observed effect are planning illustrations, not observed power. The assumptions stated for those illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are hypothetical planning assumptions; they do not describe this study’s single-group design. The registry record does not report the numerical primary outcome estimate needed to assess the basis for such an illustration from the information presented in this analysis.

As a general concept, planning calculations depend on assumptions about the effect to detect, variability, allocation, and statistical method. A calculation under assumed conditions cannot show that an already completed study had adequate power, nor does it establish what the study found. The illustrations should therefore be distinguished from observed results and from the study’s own design justification. The study’s sample-size justification is not reported in the registry record.

What can be learned from the outcome list?

The registry lists 17 outcome measures and 0 analyses. Outcome descriptions identify what investigators intended to assess, while analyses and numerical results are needed to evaluate the findings. The additional outcomes include CFR at another assessment time and measures of cardiac strain and arterial stiffness. As a general statistical matter, evaluating multiple outcomes raises questions about how results are interpreted together and whether any adjustment or prioritization was specified. The statistical plan and any multiplicity strategy are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Guselkumab 100 mg: Nicotine Users", "Guselkumab 100 mg: Non-Nicotine Users")
n   <- c(3, 3)
m   <- c(-0.08, 0.173)
sp  <- c(0.2773, 0.6478)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Guselkumab 100 mg: Nicotine Users  3  -0.080  0.277  -0.769  0.609
CARM  Guselkumab 100 mg: Non-Nicotine Users  3  0.173  0.648  -1.436  1.782

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures and records 0 analyses. It identifies CFR change at Week 32 as the primary outcome and lists secondary outcomes involving CFR at Week 16, global longitudinal strain, and carotid-femoral pulse wave velocity at specified follow-up times and CFR subgroups. The outcome list alone does not show which measures were analyzed or what they found.

As a general statistical concept, multiplicity arises when researchers assess several outcomes, time points, or subgroups. Considering many results can increase the chance that some appear noteworthy by chance. A prespecified hierarchy or adjustment method can help guide interpretation, but the statistical plan and any multiplicity approach are not reported in the registry record. The record does not explain whether secondary measures were treated as exploratory or how they were intended to relate to the primary endpoint.

The registry defines baseline as the last non-missing measurement before or on the day of the first dose. It does not report the amount or pattern of missing outcome data, how missing follow-up values were handled, or whether any sensitivity analyses were conducted. The primary outcome population is described as treated participants evaluable for CFR within the stated screening and baseline range. The number analyzed is not reported in the registry record.

The description of the full analysis set says it included participants who received at least 1 dose, while the primary outcome description further restricts evaluability according to CFR measurements. The record does not provide enough analysis detail to determine how those population descriptions were applied to the reported results. Because numerical results and analysis details are absent, the effects of missing data, outcome selection, and population definitions cannot be assessed.

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: ligament rupture (12.5%).

The registry separates the safety figures by nicotine-use status among guselkumab recipients. In the nicotine-user group, 7 participants were at risk for serious adverse events and 0 were reported as affected; 7 were at risk for other adverse events and 1 was affected. In the non-nicotine-user group, 8 were at risk for serious adverse events and 1 was affected; 8 were at risk for other adverse events and 2 were affected. The reported death count was 0 in each group.

These are counts within registry safety categories, not a comparison between guselkumab and an untreated or alternative-treatment group. The nicotine categories are subgroup labels, not randomized study arms. The registry also lists ligament rupture at 12.5% as a top serious adverse event term, but does not give enough information in that listing to attribute the term to a particular subgroup or assess its context.

As a general statistical concept, safety counts should be read alongside the number at risk, follow-up duration, event definitions, and the way events were collected. These figures alone do not establish that an event was caused by treatment. The registry record does not report further event-level details or an explanatory safety analysis. They should be interpreted as descriptive reports from the study rather than as comparative estimates of risk.

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

The registry record describes a study designed to assess whether CFR changed from baseline to Week 32 during guselkumab treatment in participants with moderate to severe plaque psoriasis and intermediate cardiovascular risk. It explains the measurement procedure and identifies CFR as the primary endpoint. It also lists other cardiovascular surrogate measures for assessment.

The record does not report a numerical primary outcome result. It therefore does not show the direction or magnitude of the mean CFR change, the variation in individual changes, or the precision of an estimate. Numerical results for the secondary outcomes are also not reported in the registry record. The available information cannot establish that CFR or another surrogate marker improved, worsened, or remained unchanged.

Even if a within-group change were reported, the single-group design would limit causal interpretation. Without a concurrent comparator, change over time could reflect factors other than treatment, including natural fluctuation or measurement variability. An open-label design also means participants and study staff were not masked, though the registry does not report whether this influenced assessment.

CFR is a surrogate measure, not a direct measure of clinical cardiovascular events. As a general principle, a surrogate result should not be treated as interchangeable with evidence about clinical outcomes. The registry does not report clinical cardiovascular event results as the primary endpoint, and it does not provide enough numerical outcome information to assess the surrogate findings.

The record’s terminated status is relevant context, but the reason for termination and its implications for data collection or analysis are not reported in the registry record. It is therefore not possible to infer why the study ended or what impact termination had on the outcome assessment. Overall, the record defines the research question and methods, but does not provide the numerical evidence needed to answer the question statistically.

14. Why This Trial Matters Statistically

This study is statistically notable for the contrast between a specific physiological endpoint and a design without a concurrent comparator. CFR was defined as a ratio of blood flow during stress to blood flow at rest, with measurement described using transthoracic Doppler echocardiography and adenosine. The registry thus identifies a concrete, continuous surrogate measure and a defined follow-up time for the primary question.

At the same time, a single-group baseline-to-follow-up design answers a narrower question than a randomized comparison. It can describe change among participants with available measurements, but it cannot directly estimate how that change differs from what would have occurred under another treatment or no study intervention. This distinction matters whenever a within-group change is discussed as evidence of an intervention effect.

The record also illustrates why endpoint descriptions and outcome findings must be distinguished. It specifies the primary endpoint, population criteria, and measurement approach, but does not report the numerical result or analysis. Without the estimate and its uncertainty, readers cannot assess the size, direction, variability, or precision of the observed change. The registry’s 0 analyses further limits what can be interpreted from the posted record.

Finally, the range of listed outcomes makes statistical planning and reporting relevant. Multiple measures and assessment times can complicate interpretation, so a clear analysis plan and transparent reporting of missing data and multiplicity methods would help readers understand how findings were selected and evaluated. Those details are not reported in the registry record. The study is therefore informative about the intended measurement question and design, but not about the statistical result of that question.

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 main trial-specific limitation for interpreting the posted record is that it does not report numerical results for the primary CFR change. The registry identifies the mean and standard deviation as the planned summary, but the values and the number analyzed are not reported. Without those data, neither the magnitude nor precision of the primary finding can be assessed.

The single-group design has no concurrent control group, and the study was open-label. A change from baseline, if available, would not by itself separate treatment-related change from temporal effects or measurement variability. The record does not report whether the open-label design affected measurement or conduct.

The study is listed as terminated, but the reason for termination is not reported in the registry record. The record also does not state whether all intended follow-up measurements were completed or how termination affected the planned analysis. The analysis population is described, but the number evaluable and the completeness of outcome measurements are not reported.

The registry lists secondary outcomes and CFR subgroups, but numerical findings, missing-data methods, and multiplicity procedures are not reported. No statistical analysis plan or sample-size justification is reported in the registry record. The planning assumptions described for sample-size illustrations should not be confused with the study’s design or with observed power. Finally, CFR is a surrogate measure; the registry record does not present the primary outcome as a clinical cardiovascular event measure.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis — NCT05125679.
• Registry record last updated 2025-03-30; status last verified 2025-03.
• Results first posted 2025-01-27.
• 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 describes a Phase 4, interventional, open-label, single-group study of guselkumab in participants with moderate to severe plaque psoriasis and intermediate cardiovascular risk. Enrollment is listed as 15, and the study status is terminated. The specified regimen was 100 mg by subcutaneous injection at Weeks 0, 4, 12, 20 and 28.

The primary endpoint was mean change from baseline in CFR at Week 32, measured by transthoracic Doppler echocardiography. The registry also lists secondary outcomes involving CFR, global longitudinal strain, and carotid-femoral pulse wave velocity. It records 17 outcome measures and 0 analyses.

Numerical primary and secondary outcome results, the reason for termination, the statistical analysis plan, and missing-data methods are not reported in the registry record. The posted information defines the study question and design but does not permit assessment of the primary result’s direction, magnitude, or precision.