A Study to Investigate Interchangeability of ABP 654 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Investigate Interchangeability of ABP 654 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis (NCT04761627), a randomized phase 3 study. The primary outcome is Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (AUCtau) Between Week 52 and Week 64.

2. Clinical Question

The trial asks whether repeated switching between ustekinumab and ABP 654, compared with continued ustekinumab, produces similar pharmacokinetic exposure in participants with moderate to severe plaque psoriasis. The registry describes the study as evaluating pharmacokinetic similarity, efficacy, safety, and immunogenicity. Its primary endpoint is the area under the plasma concentration-time curve over the dosing interval between Week 52 and Week 64.

The comparison is between participants assigned to a switching regimen and participants assigned to continued ustekinumab. The switching group initially received ustekinumab up to Week 16 and, starting from Week 28, switched between ABP 654 and ustekinumab every 12 weeks up to Week 52. The continued-use group received ustekinumab up to Week 52. The posted primary pharmacokinetic parameters are based on ABP 654 in the switching group and ustekinumab in the continued-use group.

Clinical response is also described through PASI outcomes at Week 64, including percentage improvement from baseline and PASI response thresholds. These outcomes provide clinical context alongside the concentration-based primary endpoint, but they are not the same measure: pharmacokinetic exposure concerns drug concentration over time, whereas PASI outcomes concern psoriasis severity and response.

3. Trial Design

NCT04761627 is a completed, randomized, double-blinded, parallel-group phase 3 study sponsored by Amgen. The registry lists the study start as 2021-03-24 and primary completion as 2023-02-28. Its official title describes a multicenter study evaluating pharmacokinetics, efficacy, and safety of multiple switches between ustekinumab and ABP 654 compared with continued ustekinumab.

The registry lists enrollment of 494. Participants were randomized to a switching group or a continued-use group. In the continued-use group, participants received subcutaneous ustekinumab up to Week 52. In the switching group, participants initially received ustekinumab up to Week 16; starting from Week 28, they switched between ABP 654 and ustekinumab every 12 weeks up to Week 52. The registry record does not describe the treatment schedule between Week 16 and Week 28, so no further schedule should be inferred.

The primary outcome is a pharmacokinetic measure collected between Week 52 and Week 64. Blood samples were taken before the Week 52 dose and at specified times after that dose, extending through 12 weeks. The primary analysis population is described as randomized participants who received all 3 assigned investigational-product doses between Week 28 and Week 52 and had an evaluable serum concentration-time profile between Week 52 and Week 64. The record's description of the population is incomplete, and further eligibility or missing-data details are not reported in the registry record.

Other posted outcomes include PASI measures, pharmacokinetic measures, treatment-emergent adverse events, events of interest, and antidrug antibodies. The registry lists ten outcome measures and nine analyses, but numerical results are not included for every listed outcome in the information reported. The record does not report the sample-size justification, detailed statistical plan, or any interim-analysis procedures.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Participants with moderate to severe plaque psoriasis were randomized at week 28 to 1 of 2 treatment groups following a run-in period. Randomization was stratified by prior biologic use for psoriasis at baseline, geographic region, and body weight group at baseline. Dosage was weight-based to ensure similar concentration by body weight received.

Run-in Period

Reasons for not completing this period:

Post-randomization Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The PK parameter analysis set consisted of all randomized participants who received all 3 doses of the assigned investigational product between week 28 and week 52 and who had an evaluable ABP 654 or ustekinumab serum concentration-time profile between week 52 and week 64. Participants with data available are presented.

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.

Population: Baseline characteristics are presented for the full analysis set which included all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (AUCtau) Between Week 52 and Week 64, measured over Blood samples were taken pre-dose week 52; and at 2 days, 7 days, 10 days, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the week 52 dose.

The primary endpoint is area under the plasma concentration-time curve over the dosing interval, abbreviated AUCtau, between Week 52 and Week 64. It summarizes drug exposure over time across the dosing interval rather than describing a concentration at a single sampling moment. The registry reports the endpoint in hour*mcg/mL and presents geometric means with geometric coefficients of variation as the measure of dispersion.

For the switching group, the pharmacokinetic parameter is based on ABP 654; for the continued-use group, it is based on ustekinumab. The registry reports a geometric least-squares means ratio for the comparison. A ratio expresses one group's geometric least-squares mean relative to the other group's, so interpretation depends on the stated order of the comparison. The registry gives the ratio as 0.932 with a 90% confidence interval from 0.887 to 0.980.

General statistical context: pharmacokinetic endpoints are useful when the question concerns exposure to a drug over time. AUC captures both the magnitude and duration of measured concentrations across the interval, unlike a single concentration measurement. Geometric summaries are commonly used for positive measurements that may be right-skewed or vary proportionally; the coefficient of variation describes relative variability on a multiplicative scale. These general properties do not establish clinical equivalence by themselves. Formal equivalence interpretation also depends on prespecified margins and analysis details, which are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a ratio of geometric least-squares means. A least-squares mean is a model-based group estimate; the registry does not identify the model or list its adjustment variables. The ratio compares the switching group's pharmacokinetic estimate with that of the continued-use group, as specified by the reported group order. The numerical estimate is 0.932, and its 90% confidence interval is 0.887 to 0.980.

What does a confidence interval describe?

General statistical context: a confidence interval describes the uncertainty associated with an estimate under a particular statistical procedure and its assumptions. A narrower interval indicates a more precise estimate than a wider interval, but precision is not the same as absence of bias. A confidence interval is not a range of individual participant values, and it is not a statement that a particular probability of the true effect lies within the interval. The registry gives a 90% interval for the primary ratio and 90% intervals for its sponsor-reported secondary equivalence comparisons.

Why use a ratio for pharmacokinetic exposure?

General statistical context: concentrations and exposure measures are positive quantities, and proportional differences can be more meaningful than absolute differences. Comparing geometric means through a ratio expresses relative exposure. A ratio near one indicates similar estimated group values on the ratio scale, but whether the values meet a formal equivalence criterion depends on an acceptable range set before analysis. That range, and the method used to construct the primary interval, are not reported in the registry record.

The primary endpoint is summarized by geometric means and geometric coefficients of variation. General statistical context: geometric summaries are calculated on a multiplicative scale and are often suitable when positive measurements are skewed. The geometric coefficient of variation describes relative dispersion rather than dispersion in the original measurement units. It is not interchangeable with a standard deviation. The posted group values are 5144.0 for the switching group and 5768.0 for the continued-use group; the listed geometric coefficients of variation are 45.3 and 50.4, respectively.

How should the PASI comparisons be read?

The registry also reports mean percentage improvement from baseline and response percentages for PASI 75 and PASI 100 at Week 64. The recalculated continuous comparison uses a mean difference, while the response comparisons use risk differences. A mean difference expresses the separation between group averages in the original outcome scale. A risk difference expresses the difference between the proportions meeting a response definition. The recalculated confidence intervals are unadjusted and arise from simple comparisons of posted summary statistics; the record does not say that these reproduce the sponsor's analysis method.

General statistical context: an interval that includes zero for a difference is compatible with no difference under that calculation, but does not prove the groups are identical. Conversely, a small point estimate does not by itself demonstrate equivalence. For binary outcomes, uncertainty depends on both the response proportions and the amount of information available. Estimates based on a limited number of events can be imprecise even when the point estimates are close.

Why can over-dispersion matter?

General statistical context: over-dispersion occurs when observed variability is greater than a model assumes. If a model ignores that extra variability, its uncertainty estimates can be too small and its intervals too narrow. The registry does not report whether over-dispersion was assessed or relevant to these analyses. This is a general consideration, not a claim about the study's data or analysis.

The planning illustrations associated with the secondary recalculations are not observed power and are not the study's own sample-size calculation. They use the observed effects as planning inputs, with stated assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation; the illustrations consider specified fractions of the observed effect. Very small observed differences can yield very large planning requirements, but such illustrations are sensitive to the observed effect and do not establish what sample size the trial needed. The trial's own sample-size justification is not reported in the registry record.

Finally, results depend on the analysis population, handling of missing measurements, model specification, and any multiplicity strategy. The registry describes a primary pharmacokinetic analysis set based on dosing and an evaluable profile. The full analytic rules, treatment of missing data, and multiplicity procedure are not reported in the registry record. That limits independent evaluation of the estimates and of the certainty attached to them.

10. Analyses Reported by the Sponsor

The registry's primary sponsor-reported analysis is a geometric least-squares means ratio of 0.932, with a 90% confidence interval from 0.887 to 0.980, and it is labeled as an equivalence analysis. There is no recalculated primary ratio in the posted secondary recalculations, so those calculations do not provide a direct independent reproduction of the primary estimate.

For the secondary PASI outcomes, the registry reports its own equivalence comparisons. For mean PASI percentage improvement, the sponsor-reported mean difference is 0.07 with a 90% confidence interval from -2.62 to 2.77. The simple recalculation from posted summaries gives -0.08 with a confidence interval from -3.313 to 3.153. These are close in broad interpretation but are not identical. The record does not provide enough method detail to attribute the difference to a particular model, population, or rounding choice.

For PASI response outcomes, the registry reports response differences and 90% confidence intervals. The recalculated binary comparisons use unadjusted risk differences from posted summary counts. These are different analytic presentations, so they should not be treated as exact replications of the sponsor's analyses. The record does not identify the sponsor methods in detail. The sponsor's analysis is the study's reported analysis; the recalculations are descriptive checks based on the posted summaries.

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise because the registry lists multiple outcome measures and analyses, including the primary pharmacokinetic endpoint, several PASI outcomes, pharmacokinetic measures, safety outcomes, and immunogenicity. When many outcomes are tested, the chance of at least one apparently notable result can increase. General statistical context: prespecifying a primary endpoint helps identify the main comparison, while a stated multiplicity procedure explains how inference across additional tests is controlled. The registry record does not report a multiplicity adjustment strategy for the secondary outcomes.

The registry labels the primary analysis and several sponsor-reported secondary comparisons as equivalence analyses. A formal equivalence conclusion requires margins specified in advance and an analysis designed to evaluate those margins. The margins and detailed analysis plan are not reported in the registry record. The label is therefore relevant to how the sponsor framed the comparison, but the record does not contain all information needed to assess the formal equivalence framework independently.

The primary analysis population is described as randomized participants who received all 3 doses of assigned investigational product between Week 28 and Week 52 and had an evaluable serum concentration-time profile between Week 52 and Week 64. The full population description is incomplete in the registry record. The posted primary group sizes are 199.0 and 204.0; the post-randomization safety group sizes and the outcome-specific PASI group sizes differ. These populations should not be conflated, and the record does not explain all reasons for differences in analysis denominators.

Missing-data handling is not reported in the registry record. In particular, the record does not describe how missing PASI assessments, nonevaluable pharmacokinetic profiles, or incomplete follow-up were handled in each analysis. It also does not provide a full account of analysis-set definitions for every secondary outcome. These omissions limit assessment of possible bias from missing observations and the extent to which analyses preserve the randomized comparison.

The record does not report interim-analysis procedures, a detailed statistical analysis plan, or the trial's sample-size justification. Planning illustrations based on observed secondary effects are not a replacement for those design details. They should not be interpreted as observed power or evidence that the trial was sized to detect a particular effect.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: papillary thyroid cancer (0.5%), dermatillomania (0.5%), pancreatitis acute (0.5%), cholecystitis (0.5%), colon cancer (0.5%).

The safety summary separates the run-in period from post-randomization groups. In the run-in group, 14 serious adverse events were reported among 494 at risk, and 116 other adverse events were reported among 494 at risk; the record lists 2 deaths. In the post-randomization switching group, 3 serious adverse events and 55 other adverse events were reported among 217 at risk, with no deaths listed. In the post-randomization continued-use group, 2 serious adverse events and 58 other adverse events were reported among 216 at risk, with no deaths listed.

The registry also lists additional post-randomization categories with missing treatment information. Their at-risk counts and event counts are not interchangeable with the principal switching and continued-use groups. The listed serious-event terms are each shown at 0.5% and include papillary thyroid cancer, dermatillomania, acute pancreatitis, cholecystitis, colon cancer, and cerebrovascular accident. These terms should be read as registry event listings, not as evidence that treatment caused them.

General statistical context: event counts alone do not describe exposure time, severity distributions, or causal attribution. Low counts can produce substantial uncertainty, and comparisons can be affected by differing analysis populations and follow-up. The registry summary does not provide enough detail to determine whether a difference between these counts would reflect treatment, chance, or other factors. These figures are descriptive safety information, not a treatment recommendation.

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

The posted primary result describes the relative pharmacokinetic exposure measured by AUCtau between Week 52 and Week 64 for the switching regimen and continued ustekinumab. The estimate and confidence interval are consistent with the registry's stated equivalence framing, but a complete independent assessment of formal equivalence requires the prespecified margins and analysis details, which are not reported in the registry record.

The secondary PASI summaries show broadly similar clinical-response patterns between the groups. Their recalculated unadjusted intervals include no difference, which means the posted summaries do not provide a clear separation on those comparisons. This is not proof that the regimens are identical, and it is not proof that any clinically meaningful difference has been excluded. The precision and interpretation of each result depend on the interval, the endpoint, the analysis population, and the method used.

The findings also do not establish the safety of either regimen beyond the study context or show that the treatments work or do not work. The registry's adverse-event figures are descriptive counts, with separate run-in and post-randomization groupings. They do not on their own establish causation or permit a complete comparison of safety over time.

The randomized, double-blinded design supports a comparative study question, but interpretation still depends on the analysis sets and missing-data methods. The record does not fully report those methods, the equivalence margins, the multiplicity approach, or the complete statistical plan. This means the posted results are useful for understanding the reported comparison, while important details needed for a comprehensive appraisal remain unavailable in the registry record.

General statistical context: an estimate is not a guarantee about future participants or settings. Confidence intervals quantify uncertainty under the analysis assumptions, not every source of uncertainty. The result should therefore be read as a registry-reported comparison of the studied regimens and endpoints, rather than as a universal conclusion about all patients, treatment schedules, or outcomes.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary question concerns pharmacokinetic comparability after repeated switching, not simply a difference in a clinical-response score. AUCtau captures exposure over the dosing interval, and the comparison uses a geometric least-squares means ratio. That scale is suited to relative exposure questions, but it makes the equivalence margins and ratio interpretation central to judging the result.

The treatment contrast also has a specific sequence: participants in the switching group initially received ustekinumab, then switched between ABP 654 and ustekinumab beginning at Week 28, while the comparator continued ustekinumab through Week 52. The primary pharmacokinetic window follows the Week 52 dose. Accordingly, the estimate addresses the exposure comparison in that study context and does not answer every possible switching schedule or timing question.

The study reports both sponsor analyses and allows straightforward secondary recalculations from group summaries. Their roles differ. Sponsor-reported analyses reflect the study's stated equivalence comparisons, while recalculations are transparent, unadjusted comparisons based on summary statistics. Similar-looking estimates do not ensure that methods are identical, and differences should not be resolved by assuming a particular model or adjustment that the record does not describe.

The study also illustrates why a point estimate alone is inadequate. The confidence interval describes precision, and a formal equivalence assessment requires a prespecified acceptable range. Without the margins and full statistical plan, readers can see the reported estimate and uncertainty but cannot reconstruct every step behind the sponsor's formal conclusion. This is a useful distinction for interpreting equivalence claims in clinical trials more generally.

Finally, the secondary clinical outcomes and safety counts contribute context without replacing the primary endpoint. The available record supports a focused reading of the reported pharmacokinetic comparison and selected PASI results, while missing details about multiplicity, missing data, and analysis populations constrain broader conclusions.

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 registry record does not report the equivalence margins for the primary pharmacokinetic analysis. It also does not identify the model, covariates, or full method used to derive the geometric least-squares means ratio and its confidence interval. This prevents an independent reconstruction of the sponsor's formal equivalence assessment.

The primary analysis population is limited to participants with specified dosing and evaluable pharmacokinetic profiles. The record does not fully explain how participants without evaluable profiles were handled or how missing observations were treated. The posted primary group sizes differ from the outcome-specific PASI group sizes and from the post-randomization safety at-risk counts; reasons for these denominator differences are not fully described.

Only some secondary outcomes have detailed numerical results in the registry record. Although additional pharmacokinetic, safety, and immunogenicity outcomes are listed, their numerical findings are not reported in the available information. The secondary comparisons calculated from posted summaries are unadjusted and should not be read as reproductions of the sponsor's full methods.

The registry does not report the multiplicity strategy, detailed statistical analysis plan, interim-analysis procedures, or sample-size justification. The study's sample-size assumptions therefore cannot be assessed from this record. The planning illustrations based on observed effects are not the trial's design calculations and do not represent observed power.

The safety data are presented as event counts across run-in, post-randomization, and missing-treatment categories. The record does not provide a complete account of exposure duration, event adjudication, or causal attribution. The listed event terms and counts are descriptive and cannot, by themselves, establish comparative risks.

Finally, the registry's treatment descriptions do not state the schedule between Week 16 and Week 28 for the switching group. The reported comparison should be understood from the explicit schedule details available, without filling in that interval by assumption.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Investigate Interchangeability of ABP 654 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis — NCT04761627.
• Registry record last updated 2024-01-11; status last verified 2024-01.
• Results first posted 2024-01-11.
• 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

NCT04761627 is a completed randomized, double-blinded, parallel-group phase 3 study sponsored by Amgen, with enrollment listed as 494. It compared switching between ustekinumab and ABP 654 with continued ustekinumab in participants with moderate to severe plaque psoriasis.

The primary outcome was AUCtau between Week 52 and Week 64. The registry reports a geometric least-squares means ratio of 0.932 with a 90% confidence interval from 0.887 to 0.980 and labels the comparison as equivalence. Selected Week 64 PASI results show broadly similar group summaries; the unadjusted recalculations do not show a clear separation.

Important interpretive details, including equivalence margins, multiplicity procedures, missing-data methods, and the full statistical plan, are not reported in the registry record. Safety counts are descriptive and should not be interpreted as establishing causation.