Secukinumab in Tumor Necrosis Factor (TNF) - Inadequate Response (IR) Psoriasis Participants.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Secukinumab in Tumor Necrosis Factor (TNF) - Inadequate Response (IR) Psoriasis Participants. (NCT01961609), a randomized phase 3 study. The primary outcome is Percentage of Secukinumab 300 mg Participants Achieving PASI 75 at 16 Weeks.

2. Clinical Question

This clinical question is about a response threshold at a specified follow-up time, rather than a change in an average PASI score. The registry also lists a 150 mg PASI 75 outcome at 16 weeks and several secondary PASI response outcomes, including subgroup and maintenance-period outcomes. Those additional measures provide context about the outcomes registered for the trial; they do not supply the missing primary result.

3. Trial Design

The registry describes a randomized, open-label, parallel-group Phase 3 trial. It lists an enrollment of 235 and marks the trial as completed. The record gives a start date of 2013-10-09 and a primary completion date of 2016-07-12. It identifies Novartis Pharmaceuticals as the sponsor.

The two listed groups received secukinumab at 150 mg or 300 mg. The arm descriptions specify subcutaneous dosing on Day 0 and at weeks 1, 2, 3 and 4, followed by dosing every 4 weeks. They also begin to describe continuation after the primary endpoint for participants meeting NICE criteria for adequate response; the continuation details are truncated, so further treatment rules are not reported in the registry record.

Randomization means treatment assignment is determined by an allocation process rather than being chosen solely by the participant or investigator. In general, random allocation can help balance prognostic factors across groups, although it does not guarantee balance in every trial. Open-label means masking is listed as none. Knowledge of treatment assignment can affect experiences, assessments or reporting, particularly for outcomes requiring judgment. The registry record does not report whether any outcome assessment was independently masked.

A parallel design assigns participants to a treatment group and follows the groups over the trial period. The posted primary endpoint is a response percentage for the 300 mg group at 16 weeks. The registry also lists a 150 mg response outcome at that time, but does not report a primary hypothesis test or a specific primary comparison between the doses. The trial's sample-size justification, allocation ratio, randomization procedure and detailed statistical 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.

Before assignment: For both maintenance periods 1 and 2, after 16 weeks and 48 weeks, respectively, responders at both the 150 mg and 300 mg doses continued on their initiation doses during maintenance periods 1 and 2. Non-responders at 150 mg were uptitrated to 300 mg. Non-responders at 300 mg returned to routine treatment under the care of their usual clinician.

Initiation

Reasons for not completing this period:

Maintenance 1 (Weeks 17 - 48)

Reasons for not completing this period:

Maintanence 2 (Weeks 49 - 72)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The full analysis set was analyzed. Missing values with respect to response variables based on PASI score have been imputed with non-response throughout regardless of the reason for missing data (e.g. premature study discontinuation, missed visit, administrative issues).

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Secukinumab 300 mg Participants Achieving PASI 75 at 16 Weeks, measured over 16 weeks.

The primary endpoint is the percentage of participants receiving secukinumab 300 mg who achieved PASI 75 at 16 weeks. PASI combines assessments of lesion severity and affected body area into a score ranging from 0, indicating no disease, to 72, indicating maximal disease. The registry describes scoring across the head, arms, trunk and legs, using affected skin area and clinical signs including erythema, induration and desquamation.

PASI 75 is defined in the record as at least 75% improvement from baseline. This threshold turns a continuous score into a binary response: each participant either meets the threshold or does not. A response percentage is therefore an intuitive way to report how often a specified level of improvement occurred in the group. It does not show the size of improvement for participants who fall short of the threshold, nor does it describe the distribution of individual score changes.

Using a fixed follow-up time makes the response question specific to the 16-week assessment. It also means the result would depend on how missing response data are handled. The registry says missing PASI response values were imputed as non-response. The primary endpoint value and its uncertainty are not reported in the registry record, so the actual response percentage cannot be interpreted from this information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary because PASI 75 defines a threshold: a participant either reaches at least 75% improvement from baseline or does not. For a binary outcome, a response percentage is calculated from the number of participants meeting the definition relative to the relevant analysis population. The registry identifies the full analysis set as the population analyzed, but does not report the primary response count or percentage. The endpoint estimate therefore cannot be reconstructed from the record.

What does a response percentage convey?

A percentage expresses how common the defined response was in the analyzed group. It is not an average amount of improvement, and it does not show how far each participant's score changed. Threshold outcomes are straightforward to interpret, but they can conceal variation: participants just below the threshold are categorized with participants whose scores changed little, while participants at or above it are grouped together. The choice of threshold and assessment time therefore shapes what the endpoint says.

In general, uncertainty around a response percentage can be described with a confidence interval. The interval reflects sampling variability under the method's assumptions, but it does not account automatically for every possible source of bias, such as outcome measurement differences or missing-data assumptions. Since the registry does not report the endpoint estimate or its interval, neither the observed response nor its statistical precision is available for interpretation.

What does treating missing values as non-response mean?

The registry states that missing PASI response values were imputed as non-response, regardless of the reason for missing data. This is a response rule: participants without an observed response value are classified as not achieving PASI 75 for the analysis. In general, this approach can be conservative when missing participants might otherwise have responded, but it can also affect groups differently if missingness patterns differ. Its implications depend on the amount, timing and reasons for missingness, which are not reported in the registry record. The stated rule does not reveal how many values were missing.

What can be inferred from the trial structure?

Randomized allocation is intended to make treatment groups comparable on average before treatment, subject to the conduct of the randomization and chance variation. The record labels the design randomized, but does not report the randomization method, allocation concealment or baseline balance details. Open-label status means masking is listed as none. In general, knowledge of assignment can influence participant-reported outcomes, clinical decisions and assessment, though the degree depends on how outcomes are measured. The PASI definition includes clinical assessments, and the registry does not report whether assessors were masked.

The parallel design describes groups followed under their assigned dose regimens. The primary outcome concerns the 300 mg group, while a 150 mg PASI 75 outcome is listed among the secondary measures. Without a reported contrast, the primary endpoint should not be recast as a direct randomized comparison between doses. The registry lists 17 outcome measures and one analysis, but does not report the statistical procedures used for the primary endpoint, any adjustment for multiple testing, or a detailed analysis plan.

How should planning calculations be read?

General sample-size calculations estimate how many participants may be needed to detect a chosen effect under stated assumptions. The registry's planning note says its illustration is based on the observed effect, uses a two-sided significance level of 0.05, equal allocation, and a normal approximation; it describes the effect to detect as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. They do not substitute for the actual endpoint estimate, uncertainty interval or sponsor analysis. The registry's sample-size justification and its own detailed design assumptions are not reported in the registry record.

General statistical interpretation also distinguishes statistical significance from magnitude and precision. A test result depends on a null hypothesis and a model; a confidence interval helps communicate uncertainty around an estimate. Neither should be treated as a complete account of clinical relevance. For this trial, the registry record does not report a primary result, confidence interval or test statistic, so these methods cannot be used to characterize the observed PASI 75 outcome.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Secukinumab (AIN457) 300 mg")
n      <- c(118)
events <- c(77)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Secukinumab (AIN457) 300 mg  118  77  65.3  55.9  73.8  56.3  73.2  56.3  73.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures and one analysis. The primary endpoint is PASI 75 response in the 300 mg group at 16 weeks. Secondary outcomes include PASI 75 for the 150 mg group at 16 weeks, subgroup outcomes for primary inadequate response, secondary inadequate response and inadequate response after more than one anti-TNFα therapy, and PASI response measures across initiation and maintenance periods. It also lists PASI 50 and PASI 90 outcomes across those periods.

When many outcomes or subgroup analyses are considered, the chance of finding at least one apparently notable result by chance can increase. In general, multiplicity methods define how interpretation or testing accounts for a set of comparisons. The registry does not report whether a multiplicity adjustment was used, how outcomes were ordered for testing, or whether any outcomes were exploratory. A count of registered outcomes alone does not establish how many formal hypothesis tests were conducted.

For missing data, the record states that missing PASI response values were imputed as non-response regardless of the reason, including premature discontinuation, missed visits or administrative issues. The full analysis set was analyzed. This specifies the classification rule and analysis population, but the number of missing endpoint values and their distribution across groups are not reported in the registry record. The statistical analysis plan, sensitivity analyses and any alternative missing-data assumptions are also not reported. These omissions limit assessment of how robust the endpoint result would be to missingness, even if the numerical result were available.

12. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: myocardial infarction (1.7%), vomiting (1.7%), pneumonia (1.7%), diverticulitis (1.1%), lower respiratory tract infection (1.1%).

The registry's safety entries list serious adverse events for each secukinumab group. For the 150 mg group, the serious-event fields show 115 at risk and 14 affected. For the 300 mg group, they show 179 at risk and 24 affected. These are descriptive group entries; the registry record does not provide a comparative statistical analysis for them in the information available for this analysis.

The record also lists selected serious adverse event terms with percentages: myocardial infarction, vomiting and pneumonia at 1.7% each; diverticulitis, lower respiratory tract infection and cerebrovascular accident at 1.1% each. These percentages should be read as the registry's reported term values. The record does not provide further details about event timing, recurrence, overlap between terms or the denominator used for each percentage. A participant may have more than one event, so term counts or percentages should not be treated as mutually exclusive categories unless the record specifies that rule.

The other adverse-event fields list 115 at risk and 88 affected for the 150 mg group, and 179 at risk and 152 affected for the 300 mg group. The record does not report death counts. These entries do not establish whether an event was caused by treatment, and they do not by themselves support a comparison of safety between doses. Interpretation requires context about event definitions, follow-up, severity, exposure and analysis methods, which is not reported in the registry record.

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

The trial record identifies a randomized Phase 3 evaluation of secukinumab in participants with moderate to severe chronic plaque psoriasis who had an inadequate response to anti-TNFα therapy. It specifies two dose groups and names PASI 75 response at 16 weeks in the 300 mg group as the primary endpoint. This describes the question the trial registered, not the result of that question.

The primary response percentage, its confidence interval and a primary statistical test are not reported in the registry record. It is therefore not possible to state how many participants achieved PASI 75, how precisely the response was estimated, or whether the posted evidence supports a difference between doses. The presence of a 150 mg group does not alone establish that the primary analysis compared it directly with the 300 mg group.

More generally, a registered endpoint is a planned measurement, while an outcome estimate is evidence about what was observed. A response threshold captures whether a defined level of improvement was reached; it does not describe every participant's change or the full distribution of PASI scores. The missing-as-non-response rule also forms part of the endpoint's interpretation, because it determines how participants without observed response data are classified.

The safety entries provide descriptive adverse-event information, including serious event fields and selected event-term percentages. They do not show causality or comparative safety on their own. The record does not report deaths, and does not provide a complete statistical safety analysis in the information. Overall, the registry establishes the design, treatment groups and response definition, but the absent outcome results prevent conclusions about the observed efficacy endpoint or its precision.

14. Why This Trial Matters Statistically

This trial is statistically notable for the way its registered primary question is framed: a binary PASI response threshold at a defined follow-up time in a population described as having an inadequate response to TNFα antagonists. That combination makes the target outcome clear, while also limiting the scope of what the endpoint can show. The response percentage would describe whether participants crossed the threshold, not the size or distribution of score changes.

The randomized, parallel-group design and two listed doses make allocation and dose regimen central features of the trial record. At the same time, the primary endpoint is stated for the 300 mg group rather than as an explicit dose-to-dose contrast. Statistical interpretation must keep the registered endpoint separate from any possible comparison that may have been planned or conducted but is not reported.

The stated missing-data rule matters because it classifies missing PASI response measurements as non-response. This is part of the definition of the analyzed response outcome, not a minor reporting detail. Without the number and pattern of missing measurements, readers cannot assess how much that rule influenced the estimate.

The record also lists secondary response outcomes, including subgroup and maintenance-period outcomes. Multiple endpoints can provide a broader view of treatment response, but they raise questions about analysis hierarchy and multiplicity. Those methods are not reported. Finally, the primary outcome result itself is absent. The record therefore illustrates an important distinction in trial reporting: knowing the design and endpoint is not enough to evaluate the observed effect or its uncertainty.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation is that the registry record does not report the primary PASI 75 result at 16 weeks. It also does not report a confidence interval, test statistic or primary p-value. The primary response rate and its precision therefore cannot be assessed. The registry identifies a 150 mg secondary PASI 75 outcome, but its numerical result is not reported in the information available for this analysis.

The record does not explain the trial's sample-size justification, detailed statistical plan, randomization method or allocation concealment. It lists one analysis, but does not specify the primary comparison or report multiplicity procedures. The registered outcome list includes subgroup and period-specific measures, yet their analysis methods and results are not reported.

Missing PASI response values were treated as non-response, but the record does not state how many values were missing, why they were missing in practice, or whether sensitivity analyses were performed. The response percentage could be affected by this rule, and its impact cannot be evaluated without those details.

The enrollment entry is 235, while the safety fields list group-specific at-risk counts of 115 and 179. The registry record does not explain the relationship between these figures, so they should not be reconciled by assumption. The safety information also lacks details needed to interpret selected event-term percentages, including their denominators and whether events overlap. Death counts are not reported in the registry record. These reporting gaps limit both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Secukinumab in Tumor Necrosis Factor (TNF) - Inadequate Response (IR) Psoriasis Participants. — NCT01961609.
• Registry record last updated 2019-03-18; status last verified 2018-12.
• Results first posted 2019-03-18.
• 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 completed, randomized, open-label, parallel-group Phase 3 trial sponsored by Novartis Pharmaceuticals. It lists enrollment of 235 and identifies participants with moderate to severe active chronic plaque psoriasis who had an inadequate response to anti-TNFα therapy. The record gives dates of 2013-10-09 for study start and 2016-07-12 for primary completion.

Participants were assigned to listed secukinumab 150 mg or 300 mg groups, with subcutaneous loading followed by dosing every 4 weeks. The primary endpoint was PASI 75 response in the 300 mg group at 16 weeks. Missing PASI response values were imputed as non-response in the full analysis set.

The registry record does not report the primary endpoint result, its precision or a primary comparison test. It lists secondary PASI outcomes and descriptive adverse-event entries, but the information available does not establish comparative efficacy or safety conclusions.