Long-Term Effects of Infliximab in the Treatment of Moderate to Severe Psoriasis [Extension of Study P04271, NCT00251641] (P04563): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-Term Effects of Infliximab in the Treatment of Moderate to Severe Psoriasis [Extension of Study P04271, NCT00251641] (P04563) (NCT00358670), a randomized phase 3 study. The primary outcome is Number of Participants Who Achieved Psoriasis Area and Severity Index 75 (PASI75) Response at Week 128.

2. Clinical Question

The central comparison is between two schedules of the same biological treatment, not between infliximab and a different drug. The extension was intended to assess efficacy and safety during long-term maintenance therapy versus intermittent therapy. The original Study P04271 had compared infliximab with methotrexate, but that earlier comparison is background to this extension rather than the comparison posed by its primary endpoint.

The primary endpoint asks about response at a specified time point, Week 128, and uses the original baseline from Study P04271 as its reference. The registry record states that no subjects completed 128 weeks of therapy because the extension ended early. Consequently, the record does not provide a completed Week 128 response count for either schedule. The clinical question is clear, but the posted record cannot answer it with the planned endpoint data.

3. Trial Design

This was a Phase 3, randomized, parallel-group, open-label study of long-term infliximab treatment. The registry record lists 441 participants enrolled and identifies the condition as psoriasis. The study began in 2006-05, had a primary completion date of 2009-01, and is recorded as terminated.

Participants were assigned to maintenance or intermittent infliximab. The maintenance schedule was 5 mg/kg every 8 weeks without a treatment interruption. The intermittent schedule began after a 50% reduction in PASI from the baseline in Study P04271 and consisted of infusions at Weeks 0, 2, 6 and 14. Both arms therefore used infliximab, while differing in the timing and continuity of treatment.

Randomization is intended, in general, to reduce systematic differences between comparison groups at the time of assignment. A parallel-group design means participants are followed in their assigned groups rather than crossing between schedules as part of the described comparison. Open-label means masking was not used; the registry record does not report that participants or study personnel were blinded.

The study was an extension of Study P04271, a Phase 3b study described in the registry as a 26-week comparison of infliximab and methotrexate. The extension’s stated objective was to assess long-term maintenance versus intermittent infliximab. During an interim safety evaluation, the registry narrative reports a higher incidence of serious and severe infusion reactions in the intermittent arm than in the maintenance arm. The sponsor terminated the trial in response, and the registry narrative says the label would be updated to reflect the information about re-induction. Details of the randomization procedure, allocation concealment, and the protocol’s statistical analysis plan are 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: Due to the early termination of the study, no subjects completed 128 weeks of therapy.

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 Number of Participants Who Achieved Psoriasis Area and Severity Index 75 (PASI75) Response at Week 128, measured over 128 weeks.

The primary endpoint is the number of participants who achieved a Psoriasis Area and Severity Index 75 response at Week 128. PASI75 is defined in the registry as a >=75% improvement in PASI from the original baseline in Study P04271. PASI is a measure of psoriasis area and severity; the endpoint therefore represents a specified degree of improvement relative to the earlier study’s baseline.

In general, a threshold response endpoint can make a clinical outcome easier to interpret as a count of participants meeting a defined criterion. It also reduces a range of possible score changes to a yes-or-no classification at the selected threshold and time point. That simplicity comes with limits: the endpoint does not by itself describe the size of improvement among responders or the range of score changes among nonresponders.

The registry record gives a timeframe of 128 weeks but states that no subjects completed 128 weeks of therapy because of early termination. It does not report the number achieving PASI75 at that time. Thus, the endpoint is defined, but a Week 128 response result is not available in the registry record. Other listed outcomes include PASI75 at Week 52 and Week 100 and PASI area-under-the-curve measures over 6-month and 12-month periods; their numerical results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group comparison with no masking. These design features matter when interpreting an intended comparison, but the record does not give the detailed statistical methods used for efficacy or safety analyses. No analysis is listed. In particular, the registry record does not report a model, an analysis population, an adjustment strategy, a confidence interval, or a statistical test for the primary endpoint.

What randomization contributes

In general, randomization assigns participants to groups by chance and is intended to make groups comparable on average at the start of a trial. It can reduce the influence of measured and unmeasured baseline characteristics on a comparison, but it does not guarantee that groups will be identical. Its interpretation also depends on maintaining and documenting the assigned groups and on how outcomes and missing observations are handled. The registry identifies the study as randomized but does not report the allocation sequence, allocation concealment, or details of the assignment process.

The parallel-group structure means the two infliximab schedules are the groups of interest. The comparison is not between infliximab and methotrexate in this extension. The earlier Study P04271 comparison is described as background, and its baseline is used to define the PASI75 response in the extension. The registry does not report additional analytic details connecting data from the earlier study with the extension’s analysis.

What an open-label design means

In general, an open-label trial does not mask the assigned treatment schedule from participants and study personnel. Awareness of assignment can affect care, reporting, or assessment, depending on the outcome and trial procedures. PASI75 is a threshold based on a clinical score, but the registry does not say whether outcome assessors were separately blinded or how PASI assessments were conducted. It would be inappropriate to assume either assessor masking or its absence beyond the recorded statement that the study was open-label.

How the primary outcome is structured

The primary outcome is a count of participants meeting a threshold at Week 128, with response defined as a >=75% improvement in PASI from the original Study P04271 baseline. In general, a binary response outcome allows a comparison of the proportion meeting a criterion in each group. Its interpretation depends on the definition, assessment time, and participants included in the analysis. Here, the endpoint’s time point is specified, but no subjects completed 128 weeks and the response counts are not reported. As a result, no efficacy comparison can be reconstructed from the registry record.

The additional outcomes are response counts at Week 52 and Week 100 and PASI area-under-the-curve measures over 6 and 12 months. In general, area under the curve combines measurements across time into an overall measure over a specified period; a time-adjusted form can express an average over that period. The registry identifies these outcomes but does not report their numerical results or the analysis procedures used to calculate them.

Uncertainty and statistical tests

In general, a confidence interval describes a range of values compatible with an estimate under the assumptions of the analysis; its width conveys precision. A p-value, when reported, summarizes how compatible data are with a specified null model and is not a measure of clinical importance. Neither confidence intervals nor p-values for the efficacy comparison are reported in the registry record. No effect estimate is reported for the primary endpoint, so there is no posted estimate whose precision can be judged.

General planning calculations can illustrate how a proposed study size might relate to an assumed effect and a chosen statistical threshold. The planning framework described for this record uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. Such illustrations are not the trial’s own design justification and are not observed power. The registry does not report a sample-size justification, and the primary endpoint does not yield an observed effect in the posted record from which to make a single comparison. The listed framework should therefore not be read as evidence that the trial was designed or powered for a particular effect.

Why over-dispersion can matter in general

For count outcomes, over-dispersion means that observed variability exceeds what a chosen statistical model expects. If it is ignored, standard errors can be too small and uncertainty can appear narrower than it is. This is a general consideration, not a reported finding about this trial: the registry does not identify a count model or report a dispersion assessment. Likewise, no particular outcome distribution, adjustment, or model should be inferred from the fact that outcomes include counts and score summaries.

Overall, the design and outcome definitions are available, but the record does not report the detailed analysis methods or efficacy estimates. The most defensible statistical interpretation is limited to the design, endpoint definition, early termination, and posted safety information.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint at Week 128 and several secondary outcomes: PASI75 response at Week 52 and Week 100, plus PASI area-under-the-curve measures over 6 and 12 months. Considering multiple outcomes or time points raises a general multiplicity issue: when many comparisons are examined, the chance of at least one apparently unusual result can increase. Trial protocols commonly specify how outcomes and tests are prioritized or adjusted, but the statistical plan and any multiplicity procedure are not reported in the registry record. No outcome analyses are listed, so no adjustment method or hierarchy can be assessed.

The registry’s primary-endpoint description states that no subjects completed 128 weeks of therapy because the study was terminated early. This explains why the planned endpoint was not completed, but the record does not report the number of participants with missing assessments at earlier time points, reasons for missing measurements beyond the stated early termination, or the methods used to handle missing data. It also does not report whether any analysis used observed cases, imputation, or another approach; none should be assumed.

The record identifies enrollment and safety groups at risk, but does not specify the analysis population for efficacy, such as whether analyses followed assigned groups or included only participants with particular measurements. The number of participants enrolled is not, by itself, a description of the denominator used for each outcome analysis. Details of protocol deviations, withdrawals, and follow-up by arm are not reported in the registry record. These omissions limit assessment of both the intended analysis and the potential consequences of incomplete follow-up.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infusion related reaction (3.7%), intervertebral disc protrusion (0.9%), diverticulitis (0.9%), pneumonia (0.9%), arthralgia (0.9%).

The adverse-event figures list 24 participants affected by serious adverse events among 222 at risk in the maintenance group and 23 among 219 at risk in the intermittent group. For other adverse events, the listed figures are 95 among 222 at risk in maintenance and 97 among 219 at risk in intermittent treatment. These are descriptive counts and denominators; no comparative statistical analysis or uncertainty interval is reported in the registry record.

The registry also lists serious-event terms, including infusion-related reaction at 3.7%, intervertebral disc protrusion at 0.9%, diverticulitis at 0.9%, pneumonia at 0.9%, arthralgia at 0.9%, and atrial fibrillation at 0.5%. These term-specific percentages should be read as event listings, not as a complete account of all safety outcomes or as proof that treatment caused an event. Death counts are not reported in the registry record.

The record’s narrative separately states that an interim safety evaluation found a higher incidence of serious and severe infusion reactions in the intermittent arm and that the sponsor terminated the trial as a consequence. It gives no numerical comparison for that specific finding. The overall serious-event counts should not be used to negate or quantify the narrative’s finding, because the registry does not explain how the measures relate.

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

This trial record supports a limited set of conclusions about what was planned and what was posted. It describes a randomized, open-label, parallel-group extension comparing maintenance and intermittent infliximab in adults with moderate to severe plaque-type psoriasis. The primary question concerned PASI75 response at Week 128. The registry reports that no subjects completed 128 weeks of therapy and does not provide a Week 128 response count or an efficacy comparison.

The record does describe the reason for termination: during an interim safety evaluation, a higher incidence of serious and severe infusion reactions was observed in the intermittent arm than in the maintenance arm. This is a finding reported in the registry narrative, but its numerical estimate and statistical uncertainty are not given. The adverse-event listings provide selected counts and event terms, but they do not replace a full comparative safety analysis.

The absence of a completed primary outcome does not establish that the schedules had equal efficacy, that one was more effective, or what the result would have been with continued follow-up. It also does not mean that the study had no safety information: the registry reports selected safety figures and the sponsor’s stated reason for termination. These pieces of information address different questions and should be interpreted separately.

More broadly, a trial’s design describes how investigators intended to compare groups, while results describe the outcomes actually observed and analyzed. Here, the design and endpoint are specified, but the efficacy analyses are not reported. The registry also does not provide the analysis populations, missing-data methods, or uncertainty estimates needed to judge the precision and robustness of an efficacy comparison. The evidence in the record is therefore insufficient to quantify a long-term efficacy difference between the schedules.

13. Why This Trial Matters Statistically

This study is statistically notable because its planned primary endpoint was tied to a long follow-up time, while the registry records early termination before any subjects completed that time point. That creates a clear gap between the question the trial set out to answer and the outcome information available in the registry. A well-defined endpoint cannot support an efficacy conclusion when the required endpoint observations are not reported.

The trial also illustrates why safety monitoring can alter the course of a randomized study. The registry narrative links termination to an interim finding about serious and severe infusion reactions in the intermittent arm. Such a decision changes the amount and timing of follow-up available for efficacy outcomes. It also means that the posted record must be read as an interrupted study, rather than as a completed long-term comparison.

Statistically, early stopping can complicate interpretation because outcome availability may differ from the original plan, and the reasons for stopping may be related to events occurring during follow-up. General methodological principles call for transparent reporting of stopping decisions, analysis populations, missing-data handling, and outcome estimates. The registry record gives the termination rationale but does not report the analysis details or numerical efficacy results needed to evaluate these issues fully.

Finally, this extension compares treatment schedules rather than active treatment with no treatment or with a different drug. That distinction shapes the estimand: the intended comparison concerns maintenance versus intermittent use of infliximab. The trial’s design and its safety narrative matter, but they cannot substitute for the missing Week 128 outcome data. The record is an example of why planned endpoint definitions, observed follow-up, and actual analysis results must be considered together.

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.

The primary limitation for interpretation is that no subjects completed 128 weeks of therapy, and the registry does not report the primary PASI75 response count. The planned long-term efficacy comparison therefore cannot be evaluated from the posted record. The record also gives no numerical results for the listed secondary outcomes, including PASI75 at Week 52 and Week 100 and PASI area-under-the-curve measures over 6 and 12 months.

The study is recorded as open-label, and the registry does not state whether outcome assessors were masked. It does not report the allocation procedure, analysis populations, methods for missing data, or details of the statistical analysis plan. These omissions prevent assessment of how the intended comparison was implemented and analyzed. The record reports no inferential analyses for the listed outcomes.

For safety, the narrative reports a higher incidence of serious and severe infusion reactions in the intermittent arm but does not give a numerical estimate or uncertainty interval. The posted overall serious-event counts do not explain the specific comparison described in the narrative. The record does not report death counts, and the listed event terms alone do not provide a complete comparative safety profile.

Enrollment and the stated numbers at risk offer context, but they do not establish outcome completeness or the denominator used for each efficacy analysis. The registry record does not report participant flow by arm or the reasons for missing measurements beyond early termination. These limitations mean the posted record can describe the intended design, the endpoint, termination, and selected safety information, but cannot support a precise long-term efficacy comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Long-Term Effects of Infliximab in the Treatment of Moderate to Severe Psoriasis [Extension of Study P04271, NCT00251641] (P04563) — NCT00358670.
• Registry record last updated 2017-04-11; status last verified 2017-03.
• Results first posted 2010-11-19.
• 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

This Phase 3 extension study compared maintenance with intermittent infliximab in adults with moderate to severe plaque-type psoriasis. It was randomized, parallel-group, and open-label, with 441 participants enrolled. The primary endpoint was PASI75 response at Week 128, defined as a >=75% improvement from the original Study P04271 baseline.

The registry records the study as terminated and states that no subjects completed 128 weeks of therapy. It reports no primary or secondary efficacy analyses. The termination narrative attributes the decision to an interim safety finding of a higher incidence of serious and severe infusion reactions in the intermittent arm. Selected adverse-event counts and terms are posted, but the record does not give a numerical estimate for that specific comparison or a detailed statistical analysis plan.