Study of Efficacy and Safety of Secukinumab in Patients With Non-radiographic Axial Spondyloarthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Efficacy and Safety of Secukinumab in Patients With Non-radiographic Axial Spondyloarthritis (NCT02696031), a randomized phase 3 study. The primary outcome is The Number and Percentage of TNF Naive Participants Who Achieved an Assessment of Spondylo Arthritis International Society (ASAS) 40 Response at Week 16.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, quadruple-masked, parallel-group study comparing secukinumab with placebo in patients with non-radiographic spondyloarthritis. The registry lists enrollment of 555 and the status as completed. The study start was 2016-04-29, and primary completion was 2019-07-01. These registry dates describe the record and do not, by themselves, establish how long any individual participant was followed.

The core phase included three groups: secukinumab 150 mg with a loading schedule, secukinumab 150 mg without a loading schedule, and placebo. The placebo schedule was matched to the dosing pattern described for the core phase. The registry describes the study purpose as assessing efficacy, safety, and tolerability at Week 16 and Week 52, and longer-term outcomes through Week 104.

After the core phase, an optional extension was described. It included a randomized dose-escalation treatment period lasting 16 weeks and a continuous-treatment period for up to Week 208. Extension groups included core-phase responders assigned to 150 mg or 300 mg, and core-phase non-responders receiving 300 mg open-label. These later treatment paths are not the same comparison as the randomized placebo-controlled Week 16 primary analysis.

The posted primary endpoint concerns only TNF-naive participants, while the trial enrollment figure refers to the study as a whole. The outcome-specific group counts therefore should not be treated as interchangeable with overall enrollment or with the sizes of other analysis populations. Details such as the original sample-size justification and the planned statistical analysis procedure 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.

Up to Week 24

Reasons for not completing this period:

Up to Week 52

Reasons for not completing this period:

Up to Week 104

Reasons for not completing this period:

Extension Phase From wk 104 to wk 208

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subset of TNF naive patients

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 The Number and Percentage of TNF Naive Participants Who Achieved an Assessment of Spondylo Arthritis International Society (ASAS) 40 Response at Week 16, measured over Week 16.

The primary endpoint counts TNF-naive participants who achieved an Assessment of SpondyloArthritis International Society 40 response at Week 16. ASAS response criteria draw on patient global assessment, back pain, physical function, and inflammation as the four main domains. The endpoint description also identifies spinal mobility and C-reactive protein as additional assessment domains. A higher visual-analogue-scale score represents greater severity.

For ASAS40, a participant must improve by at least 40% and at least 2 units on a scale of 10 in at least three of the four main domains, without worsening in the remaining domain. This composite rule captures improvement across several aspects of disease activity and function rather than relying on a single measure. A response count makes the outcome readily interpretable as the number meeting the stated criteria in each group.

The endpoint is assessed at Week 16, an early time point in the core phase. It does not describe the full course of symptoms, later outcomes, or every component of the response separately. It also does not establish whether an individual participant’s improvement was sustained after the assessment. The registry record’s stated primary population is a subset of TNF-naive patients, so the result should be interpreted within that population rather than assumed to represent every participant enrolled.

7. Results Posted in the Registry

• Secukinumab, Load, Core Phase: 41.5% (68/164) versus 29.2% (50/171) on control; risk difference 12.2 percentage points (95% CI 2.1 to 22.4), risk ratio 1.42 (1.06–1.91); unadjusted two-proportion z-test p = 0.019.
• Secukinumab, No Load, Core Phase: 42.2% (70/166) versus 29.2% (50/171) on control; risk difference 12.9 percentage points (95% CI 2.8 to 23.1), risk ratio 1.44 (1.08–1.93); unadjusted two-proportion z-test p = 0.013.

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.

The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 20 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:
  • Secukinumab, Load, Core Phase: 56.8% (105/185) versus 45.7% (85/186) on control; risk difference 11.1 percentage points (95% CI 0.9 to 21.2), risk ratio 1.24 (1.02–1.52); unadjusted two-proportion z-test p = 0.033.
  • Secukinumab, No Load, Core Phase: 58.2% (107/184) versus 45.7% (85/186) on control; risk difference 12.5 percentage points (95% CI 2.4 to 22.6), risk ratio 1.27 (1.04–1.55); unadjusted two-proportion z-test p = 0.017.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Secukinumab, Load, Core Phase than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Secukinumab, No Load, Core Phase than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 5/6 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:
  • Secukinumab, Load, Core Phase: 40.0% (74/185) versus 23.7% (44/186) on control; risk difference 16.3 percentage points (95% CI 7.0 to 25.7), risk ratio 1.69 (1.24–2.31); unadjusted two-proportion z-test p = <0.001.
  • Secukinumab, No Load, Core Phase: 35.9% (66/184) versus 23.7% (44/186) on control; risk difference 12.2 percentage points (95% CI 3.0 to 21.5), risk ratio 1.52 (1.10–2.09); unadjusted two-proportion z-test p = 0.010.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Secukinumab, Load, Core Phase than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Secukinumab, No Load, Core Phase than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society Partial Remission (ASAS PR)

• 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:
  • Secukinumab, Load, Core Phase: 21.6% (40/185) versus 7.0% (13/186) on control; risk difference 14.6 percentage points (95% CI 7.7 to 21.6), risk ratio 3.09 (1.71–5.59); unadjusted two-proportion z-test p = <0.001.
  • Secukinumab, No Load, Core Phase: 21.2% (39/184) versus 7.0% (13/186) on control; risk difference 14.2 percentage points (95% CI 7.3 to 21.2), risk ratio 3.03 (1.67–5.49); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Secukinumab, Load, Core Phase than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Secukinumab, No Load, Core Phase than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes covering additional ASAS response definitions, partial remission, disease activity, physical function, and quality of life. Among the secondary response outcomes with numerical results in the record, the counts meeting response criteria are higher in both secukinumab core-phase groups than in placebo. This broad direction is consistent with the primary ASAS40 comparison, but the secondary measures use different definitions and should not be treated as interchangeable with ASAS40.

These results add context by showing that the record includes other response thresholds and a remission measure, rather than relying only on the primary endpoint. They do not establish a comprehensive pattern across every secondary outcome. The registry notes 14 posted secondary outcomes, but results for each outcome are not all detailed in the registry record for this interpretation. The named secondary outcomes also include continuous measures, for which a response count is not the relevant summary.

Secondary findings generally carry less confirmatory weight when many outcomes or time points are examined, particularly if the analysis plan does not specify how multiplicity is handled. Testing multiple hypotheses increases the chance that some results appear notable by chance. The record does not report whether a formal multiplicity procedure was planned or applied. The secondary results should therefore be viewed as supportive descriptive context, not as a substitute for the primary analysis or proof of a broad effect across every measured domain.

Differences in analysis populations and endpoint definitions also matter. The primary analysis is in TNF-naive participants, while the secondary response counts have their own reported group sizes. Results should be compared within each outcome’s defined population and time point; counts should not be combined across outcomes.

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

• The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response
• The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 20 Response
• The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 5/6 Response
• The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society Partial Remission (ASAS PR)
• Change in Bath Ankylosing Spondylitis Functional Index (BASFI)
• The Number and Percentage of Patients to Achieve a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response
• Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
• Change in Ankylosing Spondylitis Quality of Life (ASQoL) Scores at Week 16

9. Statistical Interpretation

10. Statistical Methods Explained

What does a binary endpoint mean?

The primary outcome is binary for each participant: the participant either met the ASAS40 response definition at Week 16 or did not. The registry reports counts of participants meeting the definition and the corresponding group sizes. A binary outcome can be summarized as a response probability, a difference between probabilities, a relative risk, or an odds ratio. Each measure answers a related but distinct question, so the scale must be named when interpreting an estimate.

A risk difference describes the absolute gap between response probabilities in two groups. A relative risk compares the probabilities as a ratio. An odds ratio compares the odds of response rather than the probabilities themselves. Odds and probabilities are not identical; when an event is not rare, an odds ratio can look farther from the null value than a relative risk. For this reason, an odds ratio should not be translated directly into a percentage-point change.

Why are two effect measures present?

The simple re-calculation is based on the posted counts and gives an unadjusted risk difference. The sponsor’s registry analysis is reported as logistic regression with an odds ratio. Logistic regression is a common method for binary outcomes and can estimate an odds ratio. The registry does not report the covariates or full model specification in the registry record for this analysis, so no claim about adjustment for particular characteristics is warranted.

Unadjusted calculations use the group summaries as posted and do not account for participant-level covariates. A regression analysis may use additional information or modeling choices that are not captured by a simple calculation from counts. Differences between the numerical estimates do not automatically indicate an error: the reported measures have different scales, and the fitted model may have details not visible in the summary. The registry record does not flag a discrepancy.

How should a p-value be understood?

A p-value is a measure of how compatible the observed data are with a specified null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it quantify the size or importance of an effect. A small p-value does not remove uncertainty about the effect estimate, which is why confidence intervals are also informative.

The registry labels the primary logistic-regression analyses as superiority analyses. That label identifies the stated comparison type; it does not mean that every possible outcome or time point was tested successfully, or that the size of the effect is necessarily important to patients. The registry record does not report the complete statistical analysis plan, including the planned handling of multiple comparisons.

What does masking contribute?

The study is registered as quadruple-masked. In general, masking is intended to reduce the influence of treatment knowledge on participant experience, clinical assessment, and study conduct. The registry’s masking label does not specify in the registry record which roles were masked or how masking was maintained. It should therefore be read as the recorded design characteristic, not as evidence that masking was assessed or maintained without difficulty.

Why does the analysis population matter?

The primary result is explicitly described for a subset of TNF-naive patients. This matters because the endpoint counts and denominators belong to that defined analysis population, not automatically to all enrolled participants. The registry does not report the operational definition of TNF-naive status or further details of the primary analysis population in the information used. Interpretation should stay within the population as named in the endpoint record.

Group sizes can also vary across outcomes because different outcome records may use different analysis populations. The primary counts should not be combined with group counts for secondary outcomes or safety summaries. A count is meaningful only alongside the population, time point, and outcome definition to which it refers.

11. Confidence Intervals and Precision

A confidence interval gives a range of effect values that are reasonably compatible with the observed data under the statistical model and its assumptions. It conveys uncertainty around an estimate, rather than asserting that the true effect has a particular probability of lying within the observed interval. Wider intervals indicate less precision; narrower intervals indicate greater precision, all else equal.

For the sponsor-reported primary comparison, the odds ratio for secukinumab with loading versus placebo is 1.72, with a 95% confidence interval from 1.09 to 2.70. For secukinumab without loading versus placebo, the odds ratio is 1.76, with a 95% confidence interval from 1.12 to 2.76. Both intervals are above the null value of 1 for an odds ratio. Their widths still allow a range of possible effect sizes, so the point estimates should not be treated as exact or certain.

The recalculated risk-difference intervals use a different effect scale from the sponsor’s odds-ratio intervals. They should be interpreted as uncertainty about an absolute difference in response probability, not as another way of writing the odds ratio. The endpoints of an interval are not individual outcomes and do not describe the range of responses among participants.

Precision depends in part on the number of observations and the frequency of the outcome, but it also depends on the design and analysis. A confidence interval does not account for every possible source of uncertainty, such as limitations in the recorded analysis plan or incomplete reporting. The registry does not report enough information to assess all such sources. The intervals support a group-level reading of the Week 16 result, not a precise prediction for an individual.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations describe hypothetical future planning using the observed effect as a reference. For these binary-outcome comparisons, the figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. These calculations are not the trial’s original design justification; that justification is not reported in the registry record.

The 80% power column gives the approximate number of participants per arm under which a study would have an 80% chance of detecting the specified effect at the stated significance level, if the planning assumptions hold. The 90% power column describes the corresponding planning target for a 90% chance. Power is a design property calculated before observing a study’s results under specified assumptions; it is not a measure of how likely the result already observed is to be correct.

Rows for a smaller fraction of the observed effect require more participants per arm. This is expected because smaller differences are harder to distinguish from random variation. The illustration assumes the effect being planned for is a chosen fraction of the observed effect, not that a future study will necessarily reproduce that effect. Observed effects can be imprecise and can differ across settings.

The planning figures are therefore scenario-based illustrations, not a reconstruction of the completed study’s design process. They do not account for considerations not listed in the stated assumptions, and they should not be treated as a recommendation for a particular future study. This is not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.292; treatment proportion p₁ = 0.415; average p̄ = 0.354.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6761 = 1.3251.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6705 = 0.5643.
4. n = (1.3251 + 0.5643)² / (0.1222)² = 238.9, rounded up to 239 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.292397660818713                          # control proportion
p1 <- 0.414634146341463                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2696031)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 239 (80% power), 320 (90% power)
 75% of observed effect: n per arm = 417 (80% power), 558 (90% power)
 50% of observed effect: n per arm = 918 (80% power), 1,229 (90% power)
power.prop.test: 238.9 
Simulated power at n = 239 per arm: 0.801 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s own primary analyses use logistic regression and report odds ratios for each secukinumab schedule versus placebo. The reported odds ratio is 1.72 (95% confidence interval 1.09 to 2.70) for the loading schedule and 1.76 (95% confidence interval 1.12 to 2.76) for the no-loading schedule. The registry classifies both analyses as superiority comparisons.

The simple re-calculations instead use an unadjusted risk difference derived from the posted response counts. An odds ratio and a risk difference are different estimands, so their values are not expected to match numerically. The registry record does not provide the complete logistic-regression specification, and it would be inappropriate to assume which covariates or adjustments were used.

No discrepancy is flagged between the posted results and the re-calculations. The sponsor’s analyses remain the registry’s reported analyses, while the re-calculations offer a simple comparison from the summary counts on an absolute scale. Neither presentation removes the uncertainty reflected by the confidence intervals. The sponsor analysis does not provide a direct test comparing the loading schedule with the no-loading schedule.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several statistical hypotheses are tested, for example across multiple endpoints, time points, or treatment comparisons. If each test is considered separately without adjustment, the chance of at least one apparently positive result can increase as the number of tests grows. General methods for addressing this issue include prespecifying a hierarchy of tests or adjusting the significance threshold, but the appropriate approach depends on the planned study question and analysis strategy.

The registry lists 16 outcome measures and 36 analyses. It identifies a primary Week 16 ASAS40 endpoint and also lists several secondary outcomes. However, the registry record does not report whether the primary analysis was protected by a formal testing hierarchy, whether secondary results were adjusted for multiplicity, or how decisions about confirmatory claims were made. Consequently, the presence of reported p-values for multiple outcomes should not be read as evidence that multiplicity was controlled.

The handling of missing outcome data is also not reported in the registry record in the information available for this analysis. The record does not specify how participants without a Week 16 assessment were handled, whether imputation was used, or whether sensitivity analyses were performed. These details can affect estimates for response outcomes, particularly if missingness differs between groups or is related to response.

Analysis-population definitions beyond the stated TNF-naive subset are not reported in sufficient detail. The registry record also does not provide the original statistical analysis plan or enough information to determine whether the outcome analyses followed a prespecified plan. These omissions limit assessment of the confirmatory status and robustness of the findings. They do not establish that a particular method was or was not used; they identify information that is not reported in the registry record.

16. 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 (0.6%), tonsillitis (0.6%), arthritis (0.6%), acute coronary syndrome (0.5%), myocardial infarction (0.5%).

The registry reports serious adverse events and other adverse events in several treatment-exposure groups. In the group titled “Any AIN457 150 mg, in Core Phase and Extension Phase,” 48 participants were reported with serious adverse events among 543 at risk, and 320 with other adverse events among 543 at risk. In the group titled “Any AIN457, In Core Phase and Extension Phase,” the corresponding figures are 58 among 543 for serious adverse events and 335 among 543 for other adverse events. These group labels describe different summaries and should not be treated as separate, non-overlapping populations.

For placebo in the core phase, 8 participants among 186 at risk were reported with serious adverse events, and 67 among 186 with other adverse events. The extension-phase 300 mg group reports 11 among 254 with serious adverse events and 74 among 254 with other adverse events. The exposure periods and group definitions differ, so these counts are not a simple like-for-like randomized comparison at the Week 16 endpoint.

No deaths are reported in the listed groups. Serious adverse event terms with reported percentages include Crohn's disease, tonsillitis, and arthritis at 0.6%, and acute coronary syndrome, myocardial infarction, and pyrexia at 0.5%. These are registry summaries, not a complete assessment of causality or comparative risk. The safety figures should be read alongside the group definitions, exposure periods, and limits of registry reporting.

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

The posted primary results show that more participants met the ASAS40 response definition in each secukinumab core-phase group than in the placebo group at Week 16, within the TNF-naive subset. The sponsor-reported odds ratios and their confidence intervals summarize those comparisons on the odds scale. They support a group-level contrast at the stated time point, while retaining uncertainty about the size of the contrast.

These findings do not establish that every participant responded, that response continued after Week 16, or that the result applies to people outside the stated trial population. The registry describes longer follow-up and an optional extension, but the primary endpoint is not a substitute for results at Week 52, Week 104, or Week 208. Extension-phase treatment assignments and exposure groups also differ from the placebo-controlled core-phase comparison.

A statistically distinguishable group result is not the same as proof of clinical importance. The endpoint combines several domains into a threshold response, and the summary counts do not show the details of each person’s changes or how close non-responders came to meeting the criterion. The odds ratio should not be interpreted as an absolute increase in the chance of response.

The record also does not provide all details needed to assess missing data, multiplicity, or the full analysis plan. The safety summaries describe recorded adverse events but do not, by themselves, establish causation or settle the balance of benefits and harms. These results are evidence about a particular randomized comparison and endpoint, not medical advice or an individual prediction.

18. Why This Trial Matters Statistically

This trial illustrates why the analysis population and endpoint definition belong alongside every result. The primary outcome is not a general response among all enrolled participants: it is ASAS40 at Week 16 among the TNF-naive subset. Keeping that scope visible prevents the group counts from being mistaken for counts in the entire trial or for later extension populations.

It also demonstrates the distinction between absolute and relative effect measures. The recalculated risk difference expresses a contrast in response probabilities, while the registry’s logistic-regression analysis reports odds ratios. Those measures are related but not interchangeable. A reader who focuses only on the odds ratio could overstate what it says about an absolute change; a reader who focuses only on counts could overlook uncertainty around the comparison.

The study includes two active dosing schedules, placebo control, and an optional extension. This structure creates several clinically and statistically distinct questions: comparison of each active schedule with placebo, comparison between active schedules, and outcomes after the core phase. The primary analyses described in the registry answer the first type of question at Week 16; they do not establish a direct difference between the active schedules.

Finally, the record shows why interpretation must include reporting limits. Confidence intervals convey sampling uncertainty, while missing details about multiplicity, missing data, and analysis specifications constrain assessment of robustness. Statistical reading is not just identifying whether an estimate favors one group; it is clarifying the population, measure, time point, assumptions, and unanswered questions that define what the result can support.

19. 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 analysis applies to the registry-defined subset of TNF-naive patients, but the record does not provide further operational details about that subset. Generalizability beyond the enrolled trial population cannot be assessed from the endpoint summary alone. The listed primary endpoint is measured at Week 16, so it does not establish the longer-term course of response.

The primary sponsor analysis is reported as logistic regression, but the model specification and covariates are not reported in the registry record. The record also does not state whether the analyses followed a prespecified hierarchy or how missing endpoint data were handled. Without these details, it is not possible to fully assess analytic choices or the effect of missingness on the results.

The two active schedules are each compared with placebo in the reported primary analyses. Those results do not establish a difference between the loading and no-loading schedules. The optional extension includes changing treatment pathways and open-label treatment for one group, so extension outcomes would require their own careful interpretation rather than being treated as continued blinded placebo-controlled evidence.

Secondary outcomes span response criteria and other domains, but the registry does not report a multiplicity approach in the information. Secondary findings may therefore be less conclusive than the primary comparison. Safety summaries use groups with differing exposure descriptions and follow-up phases, and the counts alone cannot establish whether an event was caused by treatment or permit a fully comparable risk assessment.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study of Efficacy and Safety of Secukinumab in Patients With Non-radiographic Axial Spondyloarthritis — NCT02696031.
• Registry record last updated 2022-04-29; status last verified 2022-04.
• Results first posted 2020-08-07.
• 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.

23. Record Summary

NCT02696031 is a completed Phase 3 randomized, quadruple-masked, parallel-group study of secukinumab versus placebo in non-radiographic axial spondyloarthritis. The core phase compared a 150 mg loading schedule, a 150 mg no-loading schedule, and placebo. The primary endpoint was the Week 16 ASAS40 response among TNF-naive participants.

The registry reports more ASAS40 responses in each secukinumab group than in placebo, with sponsor-reported logistic-regression odds ratios above 1 and confidence intervals excluding 1. The study also describes follow-up through the core phase and an optional extension. Interpretation remains specific to the endpoint population and time point; details about multiplicity, missing-data handling, and the complete statistical plan are not reported in the registry record.