Study to Assess the Long-term Safety, Tolerability, Efficacy of Secukinumab in Pediatric Patients of Age 6 to <18 Years, With Moderate to Severe Plaque Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Long-term Safety, Tolerability, Efficacy of Secukinumab in Pediatric Patients of Age 6 to <18 Years, With Moderate to Severe Plaque Psoriasis (NCT03668613), a randomized phase 3 study. The primary outcome is Number and Percentage of Participants With PASI 75 Response.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, open-label, multicenter, parallel-group trial of secukinumab in pediatric participants with moderate to severe chronic plaque psoriasis. The registry lists an enrollment of 84. Participants were assigned to low-dose or high-dose secukinumab, with 42 participants in each arm in the posted primary outcome results. The study summary states that participants were stratified by weight and disease severity.

The primary efficacy assessment was at Week 12 and concerned PASI 75 response. The registry also lists PASI 90 response, serum secukinumab concentration, and adverse events among its secondary outcomes. The trial title describes assessment of efficacy after 12 weeks and long-term safety, tolerability, and efficacy. The posted primary comparison is specifically the Week 12 response comparison between the two dose groups.

The study was open-label, meaning treatment assignment was not masked to participants or investigators according to the registry’s masking designation. Randomization can reduce systematic differences between assigned groups, while open-label conduct can affect how outcomes are assessed or reported; the extent of any such influence is not established by the record. The registry record does not report details of the randomization sequence, allocation concealment, or the precise stratification procedure.

The registry lists the study as completed. The start date is 2018-08-29 and the primary completion date is 2019-09-19. These dates describe the registry record and do not add information about follow-up completeness or the timing of analyses. The record does not report the protocol’s sample-size justification, interim-analysis plan, or a complete statistical analysis plan.

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: A total of 92 subjects were screened of which 84 subjects completed the screening phase and were randomized to the Secukinumab Low dose and High dose groups in a 1:1 ratio.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: The FAS comprised all patients from the randomized set to whom study treatment had been assigned

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 and Percentage of Participants With PASI 75 Response, measured over Week 12.

The primary endpoint is the number and percentage of participants with a PASI 75 response at Week 12. PASI combines assessments of lesion severity and affected body area into a single score. The registry describes scoring across the head, trunk, upper limbs, and lower limbs, with severity and the extent of affected skin contributing to the final score. A PASI 75 response represents at least a 75% reduction in PASI from baseline.

This kind of endpoint translates a change in a continuous severity score into a responder outcome: each participant is classified according to whether the specified improvement threshold was reached. Reporting the number of responders makes the result interpretable as a count, while the percentage expresses that count relative to the analysis group. Because a threshold discards information about the size of changes on either side of the cut-off, it does not describe the full distribution of PASI changes. Two participants with different score changes can be classified alike if both meet the threshold, and a small difference around the threshold can change responder classification.

PASI 75 is used to summarize a substantial improvement from baseline in a standardized way. It is distinct from PASI 90, which represents a more stringent response threshold, and from PASI 100, which the registry describes as complete resolution. The endpoint alone does not establish how participants felt or functioned, nor does it describe longer-term response. The primary result concerns the specified Week 12 assessment.

7. Results Posted in the Registry

• AIN457 High Dose: 92.9% (39/42) versus 92.9% (39/42) on control; risk difference 0.0 percentage points (95% CI -11.0 to 11.0), risk ratio 1.00 (0.89–1.13); unadjusted two-proportion z-test p = 1.000.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number and Percentage of Participants With PASI 90 Response

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • AIN457 High Dose: 76.2% (32/42) versus 69.0% (29/42) on control; risk difference 7.1 percentage points (95% CI -11.9 to 26.2), risk ratio 1.10 (0.85–1.44); unadjusted two-proportion z-test p = 0.463.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AIN457 High Dose and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes include PASI 90 response, serum secukinumab concentration, and adverse events. The available secondary efficacy comparison concerns PASI 90 response at Week 12. The observed counts are directionally higher in the high-dose arm, unlike the equal PASI 75 counts in the primary result, but the recalculated comparison is uncertain. These outcomes provide additional context on response at a more stringent threshold and on drug exposure; they do not overturn or replace the primary endpoint.

Secondary endpoints can help describe whether the overall pattern is coherent across different outcome definitions. PASI 90 is related to PASI 75, but it applies a stricter response criterion, so the two outcomes are not interchangeable. Serum concentration is a different kind of measure and does not itself establish a clinical response. Adverse events address safety rather than efficacy. Each outcome therefore answers a distinct question, and a pattern across them should be interpreted with attention to those differences.

The registry lists multiple outcome measures and analyses. When several outcomes or comparisons are examined, the chance of finding apparently notable results by chance can increase. Unless multiplicity is addressed through a prespecified testing strategy or adjustment, secondary p-values are generally less conclusive than a primary analysis specified in advance. The registry record does not report a multiplicity-control plan for the posted secondary results. Their unadjusted comparisons should therefore be treated as exploratory rather than as independent confirmatory evidence.

The registry record does not provide a complete account of the secondary analysis populations, missing-data handling, or hierarchy among secondary outcomes. The secondary results can describe the observed data, but they do not establish a definitive dose-response relationship or resolve the uncertainty in the primary between-arm comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number and Percentage of Participants With PASI 90 Response
• Secukinumab Concentration in Serum
• Summary Table of Adverse Events

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either met the PASI 75 response threshold at Week 12 or did not. The posted counts are 39 responders among 42 participants in each dose arm. For a binary endpoint, the analysis can compare the proportions of participants meeting the response definition. The recalculated contrast is expressed as a risk difference, which subtracts one group’s response proportion from the other group’s response proportion. Its reported point estimate is 0.0.

What does an unadjusted risk difference represent?

General statistical explanation: a risk difference describes an absolute contrast in the probability of an event between groups. A value of zero corresponds to equal observed proportions. “Unadjusted” means the recalculation uses the posted group counts without adjusting for other variables. Such a contrast is straightforward to interpret, but it does not account for stratification variables or other covariates. The registry record says participants were stratified by weight and disease severity, but the recalculated contrast does not incorporate that information.

The registry also reports a p-value of 1.0 for the recalculated comparison. A p-value measures how compatible the observed data are with a specified null model, under the assumptions of the test; it is not the probability that the null hypothesis is true, and it does not measure clinical importance. In this result, the p-value does not provide evidence of a difference between the dose groups. It cannot establish that the groups are equivalent.

What do the confidence intervals add?

General statistical explanation: a confidence interval describes a range of effect estimates compatible with the data and the method used, at the stated confidence level. It communicates uncertainty around the point estimate and helps readers judge which effect sizes remain plausible. The recalculated risk-difference interval extends to both sides of no difference. That means the data are compatible with more than one direction of difference, rather than identifying a precise advantage for either dose. A confidence interval is not a guarantee that the true effect lies within its bounds.

The registry also provides relative measures, including risk ratio and odds ratio, in its recalculated comparison. These express group contrasts on different scales. A risk ratio compares response probabilities, whereas an odds ratio compares response odds. They can look numerically different from a risk difference because they answer the contrast on different scales. They should not be conflated, and their interpretation depends on the event definition and the groups being compared.

How does the sponsor analysis differ?

The sponsor-reported analysis uses a Bayesian method identified as MAP and reports predicted log-OR estimates for each arm, with 95% confidence intervals. A log-OR is on the logarithmic scale of an odds ratio. The registry’s presentation gives one estimate for the low-dose group and one for the high-dose group; it does not present those two entries as the same direct risk-difference contrast produced by the recalculation. The estimates therefore should not be interpreted as if they were the recalculated between-arm effect.

General statistical explanation: Bayesian methods combine a likelihood from observed data with prior information to obtain a posterior distribution. A MAP estimate is a mode of that distribution. The role of prior information and the full model specification matter to interpretation. The registry record does not report sufficient detail to reconstruct those modeling choices. The sponsor’s listed intervals are described as 95% confidence intervals in the record; the page should retain that terminology rather than assume a different interval definition.

What are the planning illustrations?

The planning illustrations are based on the observed effect and are not the trial’s design justification or observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They show participants per arm for 80% power and for 90% power at different fractions of the observed effect. Such calculations are hypothetical planning aids: they describe the group sizes a calculation would suggest under the stated assumptions and effect scenario. They do not change the observed trial results or show that the trial had a particular probability of detecting its actual effect.

General statistical explanation: when an observed effect is used as the planning target, the estimate itself is uncertain. Planning for a smaller fraction of that effect requires a larger study under otherwise fixed assumptions, because a smaller contrast is harder to distinguish from random variation. These illustrations should not be read as a sample-size rationale documented by the investigators. The registry record does not report the original sample-size justification.

Why does a binary endpoint need careful interpretation?

General statistical explanation: converting a continuous score into a responder classification can simplify communication, but it loses information about the magnitude of change. The threshold also makes the result sensitive to participants whose scores lie near the cut-off. The responder count is therefore one useful summary, not a complete account of clinical outcomes. The registry record reports the PASI 75 count at the specified assessment; detailed individual score changes and their distribution are not reported in the registry record.

11. Confidence Intervals and Precision

The primary comparison has a point estimate of 0.0 for the unadjusted risk difference. Its confidence interval is wide enough to include differences in either direction, so the point estimate should not be treated as a precise finding of no difference. The interval communicates that the observed counts are compatible with a range of possible underlying contrasts. It does not, by itself, establish that either dose is better or that the doses are interchangeable.

General statistical explanation: precision depends on the amount of information in the data and on how variable the outcome is. For a binary endpoint, uncertainty is affected by the number of participants and the distribution of responders and nonresponders. Confidence intervals make that uncertainty visible; the point estimate alone does not. A narrow interval can rule out more effect sizes than a wide interval, but even a narrow interval must be interpreted in relation to a clinically meaningful difference and a prespecified analysis plan.

The registry’s sponsor-reported 95% confidence intervals are attached to predicted log-OR estimates for each arm. They are not the interval for the recalculated risk difference and should not be used as though they directly quantify uncertainty in that between-arm contrast. The registry record does not report enough model detail to independently assess the sponsor intervals’ construction.

The trial’s reported counts support a direct description of the observed response pattern, but they do not support a highly precise conclusion about small dose differences. The record does not report a prespecified equivalence or noninferiority margin, which would be necessary to interpret precision as evidence that any possible difference is acceptably small. The confidence interval is best read as uncertainty around an unadjusted estimate, not as a definitive boundary on all relevant effects.

12. Analyses Reported by the Sponsor

The sponsor-reported primary analyses use a Bayesian method identified as MAP and list predicted log-OR estimates of 4.862 for the low-dose arm and 4.836 for the high-dose arm. Each is accompanied by a 95% confidence interval. These are arm-specific sponsor results on a log-odds scale. The recalculation instead compares the posted responder counts between arms using an unadjusted risk difference, whose point estimate is 0.0. Because the estimands and scales differ, the values should not be compared as if they were competing estimates of one identical contrast.

The registry record does not flag a discrepancy between posted results and the recalculation. The recalculation is therefore a simple unadjusted check of the reported counts, not a replacement for the sponsor’s model-based analysis. The sponsor’s analysis should be interpreted according to its own stated method, while recognizing that the registry record does not provide enough detail to reproduce the model or assess its assumptions fully.

Neither set of results establishes equivalence between doses. The sponsor estimates are not a direct randomized contrast as presented, and the recalculated contrast is imprecise. A fuller appraisal would require the prespecified analysis plan, details of the Bayesian model and priors, handling of missing data, and any planned covariate adjustment; these are not reported in the registry record.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, but a full multiplicity strategy is not reported in the registry record. Multiplicity matters when many outcomes or comparisons are tested: without a planned approach, the overall chance of a nominally unusual result arising by chance can rise. The available record does not state whether secondary outcomes were tested in a fixed hierarchy, adjusted for multiple testing, or intended as exploratory. Unadjusted secondary results should accordingly receive less weight than a clearly prespecified primary analysis.

The primary outcome population is described as the Full Analysis Set, comprising all patients from the randomized set to whom study treatment had been assigned. That definition identifies the intended population for the reported primary result, but the record does not describe in detail how participants without an observed Week 12 assessment were treated. Missing-data counts, reasons for missingness, imputation procedures, and sensitivity analyses are not reported in the registry record. The posted counts alone cannot establish whether missingness could have affected the comparison.

The summary says participants were stratified by weight and disease severity. The recalculated comparison is unadjusted, and the registry record does not report whether the sponsor’s primary Bayesian model incorporated those strata or other covariates. The randomization procedure, allocation concealment, and detailed analysis plan are also not reported in the registry record.

The registry reports a sponsor analysis for each arm and an unadjusted between-arm recalculation. The full relationship between those analyses and the prespecified primary testing procedure is not available. Interim analyses, stopping rules, and the protocol’s sample-size justification are not reported in the registry record. Without those details, the posted results can be described and their uncertainty assessed, but some aspects of confirmatory interpretation remain unresolved.

14. 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: crohn's disease (2.4%), appendicitis (2.4%), covid-19 (2.4%), infectious mononucleosis (2.4%), tonsillitis (2.4%).

The posted safety counts report serious adverse events in 4 participants in the AIN457 Low Dose arm and 2 participants in the AIN457 High Dose arm. Other adverse events are reported for 30 participants in the low-dose arm and 27 participants in the high-dose arm. The registry reports 0 deaths in each arm. These are descriptive counts from the posted safety results and should not be treated as adjusted comparisons or proof of a causal difference between doses.

The listed serious adverse-event terms each have a reported frequency of 2.4%: Crohn's disease, appendicitis, COVID-19, infectious mononucleosis, tonsillitis, and tibia fracture. The record does not provide enough detail in these figures to assess timing, severity beyond the serious classification, relatedness to treatment, or whether a participant could contribute to more than one term. The listed terms are not a complete safety profile.

Safety counts require context, including duration of observation, exposure, definitions, and how events were collected. Those details are not reported in the registry record for these figures. The counts describe what was posted; they do not establish that an event was caused by treatment, nor do they establish the absence of risk.

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

The primary result describes the Week 12 PASI 75 responder counts in two randomized secukinumab dose groups. The posted counts are equal: 39 participants in each arm, with 42 participants in each arm reported for the primary outcome. The unadjusted risk-difference estimate is 0.0, and its p-value is 1.0. This is a summary of the observed comparison, not proof that the underlying response probabilities are identical.

The result does not compare secukinumab with placebo or another treatment. It cannot establish the effect of receiving secukinumab relative to receiving no active treatment. It also does not show whether the doses differ on outcomes other than the reported endpoint, whether any response persists beyond Week 12, or how participants’ symptoms and daily functioning changed.

A non-significant comparison does not demonstrate equivalence, and equal observed counts do not rule out a meaningful difference in the underlying effects. Equivalence or noninferiority requires a suitable design, a prespecified margin, and analyses that address that question. Such a margin is not reported in the registry record.

The endpoint is a thresholded score outcome. It communicates whether participants reached a specified reduction in PASI, but it does not describe the full range of score changes. The reported analysis also leaves questions about missing assessments, multiplicity, and model specification unanswered. Those limitations affect how firmly the result can be interpreted, particularly for secondary comparisons and longer-term conclusions.

Overall, the posted primary data show no observed difference in PASI 75 responder counts between the dose groups at the specified assessment. The uncertainty around the comparison means that this observation should not be translated into a claim that the doses have the same effect or that one dose is preferable. The registry results support a cautious statistical description rather than a treatment recommendation.

16. Why This Trial Matters Statistically

This trial illustrates why a clear comparator is essential. Both randomized groups received secukinumab, at different doses, so the primary comparison addresses the relative outcomes between those dose groups. It does not answer the separate question of how either group compares with placebo or no treatment. Keeping the estimand clear prevents an observed within-trial contrast from being generalized to a different clinical question.

It also demonstrates the distinction between a point estimate and the uncertainty around it. Equal responder counts produce an unadjusted risk-difference estimate of 0.0, but that point estimate alone is not evidence of equivalence. The confidence interval and the absence of a reported equivalence margin matter to interpretation. Statistical significance, precision, and clinical importance are related but distinct considerations.

The record gives an opportunity to compare an unadjusted recalculation from group counts with sponsor-reported Bayesian estimates. Those results use different measures and presentations. Reading them side by side requires attention to what each analysis estimates, rather than treating unlike scales as interchangeable. The record also illustrates the limits of registry-level reporting: missing-data procedures, multiplicity control, and model details are not reported in the registry record.

Finally, the secondary outcomes and safety counts show why a trial’s evidence should be read as a set of distinct questions. Efficacy thresholds, serum concentration, and adverse events are not interchangeable measures, and multiple unadjusted results do not carry the same confirmatory weight as a prespecified primary analysis. Careful interpretation keeps the numerical findings connected to the design and to the uncertainty in the available record.

17. 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 open-label design is a trial-specific limitation: treatment assignment was not masked. This may influence subjective assessments or reporting, although the registry record does not establish whether it affected the PASI assessment in this trial. The use of a standardized PASI measure helps define the response outcome, but the record does not describe any safeguards or independent assessment procedures.

The primary comparison is between two active doses and has no placebo or untreated group. It therefore cannot isolate the effect of secukinumab from changes that might occur over time or from other influences. The primary endpoint is assessed at Week 12, while the title also describes longer-term assessment; the primary comparison alone does not characterize long-term outcomes.

The posted primary group counts are modest, and the confidence interval indicates uncertainty around the unadjusted contrast. The trial record does not report an equivalence or noninferiority margin, so equal observed counts cannot support a conclusion that the doses are equivalent. The registry also does not report the sample-size justification, full randomization details, or whether the analysis accounted for the stated stratification factors.

Important analysis details are not reported in the registry record, including missing-data handling, multiplicity control, the full sponsor model specification, and the prespecified statistical analysis plan. These omissions limit independent assessment of the sponsor-reported analyses and the robustness of secondary comparisons. The listed adverse-event counts also lack information on exposure duration, event relatedness, and detailed follow-up in the registry summary. These are limitations of interpretation, not evidence that an unreported procedure or event did or did not occur.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Study to Assess the Long-term Safety, Tolerability, Efficacy of Secukinumab in Pediatric Patients of Age 6 to <18 Years, With Moderate to Severe Plaque Psoriasis — NCT03668613.
• Registry record last updated 2025-05-16; status last verified 2025-05.
• Results first posted 2021-07-23.
• 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.

21. Record Summary

NCT03668613 is a completed Phase 3 randomized, open-label, multicenter, parallel-group study of low-dose versus high-dose secukinumab in participants aged 6 to <18 years with moderate to severe chronic plaque psoriasis. The registry lists an enrollment of 84 and says participants were stratified by weight and disease severity.

The primary outcome was PASI 75 response at Week 12. The registry reports 39 responders among 42 participants in each arm. The unadjusted recalculated risk difference is 0.0, with a p-value of 1.0; the confidence interval reflects uncertainty and does not establish equivalence. Sponsor-reported Bayesian MAP analyses are presented separately as arm-specific predicted log-OR estimates.

Secondary outcomes include PASI 90 response, serum concentration, and adverse events. The registry record does not report a complete multiplicity plan, missing-data procedures, or detailed model specifications. Safety counts are descriptive and should be interpreted with the limits of the registry summary in mind.