Secukinumab Efficacy and Safety Study in Patients With Rheumatoid Arthritis and Inadequate Response to Anti-TNFα Agents.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Secukinumab Efficacy and Safety Study in Patients With Rheumatoid Arthritis and Inadequate Response to Anti-TNFα Agents. (NCT01770379), a randomized phase 3 study. The primary outcome is Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20)..

2. Clinical Question

3. Trial Design

This was a Phase III, randomized, double-blind, placebo-controlled, parallel-group study of subcutaneous secukinumab in rheumatoid arthritis. The registry identifies Novartis Pharmaceuticals as sponsor and lists enrollment as 242. The study began in 2012-10, primary completion was 2015-05, and its status is terminated. The reason for termination is not reported in the registry record.

The planned treatment groups were secukinumab 75 mg, secukinumab 150 mg, and placebo. The primary endpoint was assessed at Week 24. The official title describes a study intended to assess efficacy at Week 24 and longer-term efficacy, safety, tolerability, and usability up to 5 years. The record does not establish from the posted results whether that longer-term assessment was completed.

Randomization means the study assigned participants to treatment groups by chance; double masking means the study was designed so that treatment assignment was concealed from participants and relevant study personnel, though further operational details are not reported in the registry record. A parallel-group design compares assigned groups over the study period rather than having every participant receive each initial treatment.

The placebo-group description includes later reassignment: non-responders at Week 16 were to be reassigned to new treatment at Week 16, and responders at Week 16 at Week 24. Placebo patients were to be reassigned 1:1 to secukinumab 75 or 150 mg. This feature matters when interpreting outcomes after reassignment; the primary endpoint is the Week 24 result, with its stated non-responder imputation. Further details of treatment exposure, adherence, and post-reassignment analysis 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: At Wk 16, patients were classified as responders or non-responders. Placebo patients who were non responders were rerandomized at Wk 16 to AIN457 75 mg or AIN457 150 mg (1:1). Patients on placebo who were responders continued to receive placebo until Wk 24, these patients were re-randomized to receive AIN457 75 mg or AIN457 150 mg (1:1).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS): The FAS was comprised of 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 Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20)., measured over Week 24.

The primary endpoint was the percentage of participants achieving an American College of Rheumatology response of at least 20%, called ACR20, at Week 24. In the registry definition, this required at least 20% improvement in both tender 68-joint count and swollen 66-joint count, plus improvement in at least 3 of 5 additional measures. Those measures covered the participant's assessment of rheumatoid arthritis pain, participant and physician global assessments of disease activity, self-assessed disability using the HAQ-DI, and an acute-phase reactant, either hsCRP or ESR.

ACR20 is a composite responder endpoint: a participant must meet criteria across several disease-related measures rather than show change on only one measure. Reporting the percentage who meet the definition gives a readily interpretable group-level summary of response by a specified time. It also means that the result depends on the chosen threshold and on the handling of missing outcomes. For this endpoint, the record states that Week 24 results used non-responder imputation, under which missing response status is treated as non-response.

The endpoint identifies whether the stated response criteria were met; it does not describe the full range of individual changes or establish how durable responses were beyond the specified assessment. The Week 24 percentages therefore answer a defined, time-specific question. The registry record does not report additional details about endpoint adjudication or the rationale for selecting this particular response threshold.

7. Results Posted in the Registry

• AIN457 75 mg: 37.5% (30/80) versus 27.2% (22/81) on control; risk difference 10.3 percentage points (95% CI -4.0 to 24.7), risk ratio 1.38 (0.88–2.18); unadjusted two-proportion z-test p = 0.161.
• AIN457 150mg: 38.3% (31/81) versus 27.2% (22/81) on control; risk difference 11.1 percentage points (95% CI -3.2 to 25.5), risk ratio 1.41 (0.90–2.21); unadjusted two-proportion z-test p = 0.132.

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.

Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • AIN457 75 mg: mean -1.56 versus -1.01 on control; difference -0.55 (95% CI -1.00 to -0.10), standardized effect d = -0.38; z-test p = 0.017.
  • AIN457 150mg: mean -1.61 versus -1.01 on control; difference -0.60 (95% CI -1.05 to -0.15), standardized effect d = -0.41; z-test p = 0.009.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for AIN457 75 mg 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 mean is statistically lower for AIN457 150mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • AIN457 75 mg: mean -0.42 versus -0.13 on control; difference -0.29 (95% CI -0.49 to -0.09), standardized effect d = -0.44; z-test p = 0.005.
  • AIN457 150 mg: mean -0.39 versus -0.13 on control; difference -0.26 (95% CI -0.46 to -0.06), standardized effect d = -0.39; z-test p = 0.012.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for AIN457 75 mg 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 mean is statistically lower for AIN457 150 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants Achieving ACR50

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • AIN457 75 mg: 17.5% (14/80) versus 13.6% (11/81) on control; risk difference 3.9 percentage points (95% CI -7.3 to 15.1), risk ratio 1.29 (0.62–2.67); unadjusted two-proportion z-test p = 0.492.
  • AIN457 150mg: 18.5% (15/81) versus 13.6% (11/81) on control; risk difference 4.9 percentage points (95% CI -6.3 to 16.2), risk ratio 1.36 (0.67–2.79); unadjusted two-proportion z-test p = 0.392.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AIN457 75 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AIN457 150mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover different dimensions of rheumatoid arthritis: disease activity using DAS28-CRP, disability using HAQ-DI, and a more stringent ACR50 response threshold. Across these outcomes, the posted group summaries show a broadly similar direction for the two secukinumab groups relative to placebo: larger mean decreases in the disease activity and disability scores, and numerically higher ACR50 response percentages. This pattern offers additional descriptive context alongside the primary ACR20 outcome, but it should not be treated as an independent confirmation of it.

These measures are related but not interchangeable. A score change retains information about the scale of change, while a responder percentage classifies participants according to whether they cross a specified threshold. The results can therefore differ in apparent strength without being logically inconsistent. None of these secondary endpoints changes the definition or analysis of the primary outcome.

The recalculated unadjusted comparisons for continuous endpoints have intervals that do not include zero, while the ACR50 risk-difference intervals include zero. These results are exploratory in the sense that the registry record does not report a multiplicity adjustment, prespecified testing sequence, or sponsor analyses for the secondary outcomes. When several outcomes and contrasts are considered, some nominally notable results can arise by chance. The registry record does not report whether the secondary outcomes were intended to support formal confirmatory claims.

Accordingly, the secondary findings can inform the overall pattern and identify outcomes for further study, but they carry less weight than a prespecified primary analysis when multiplicity control and analysis hierarchy are unreported. The record also does not report missing-data handling for these secondary measures, so their estimates should be interpreted with that limitation in mind.

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

• Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP)
• Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)
• Percentage of Participants Achieving ACR50

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each participant either met the ACR20 response definition at Week 24 or did not. A percentage summarizes the fraction meeting that criterion in a group. A comparison of percentages can be expressed as a risk difference, which is the response proportion in one group minus the response proportion in the other. A difference of zero represents equal response proportions. The recalculated comparisons use this unadjusted form of the contrast.

For AIN457 75 mg versus placebo, the recalculated risk-difference point estimate is positive, and the confidence interval extends from a negative value to a positive value. For AIN457 150mg versus placebo, the estimate is also positive and its interval likewise extends across zero. This means the posted summaries do not pin down the direction of the underlying difference with high precision. The unadjusted p-values are 0.161 and 0.132, respectively. A p-value describes how compatible the observed data are with a specified null model; it is not the probability that the null hypothesis is true, nor a measure of clinical importance.

The registry's sponsor-reported comparisons use logistic regression and present odds ratios. An odds ratio compares the odds of response between groups; an odds ratio of one is the null value for no odds difference. Odds ratios and risk differences use different scales, so their numerical values are not interchangeable. Both sponsor-reported confidence intervals include one, as do not establish a clear difference from the null in those analyses. The sponsor's analysis is the study's reported analysis; recalculations based on posted summary data are useful as a separate, unadjusted check and are not a substitute for the study's full analysis.

A confidence interval gives a range of values compatible with the data under the analysis assumptions. Its width conveys precision: a wider range indicates greater uncertainty about the effect size. A confidence interval is not a guarantee that the true value lies within the particular interval, and it does not correct for unreported analysis decisions or multiplicity. General statistical interpretation also distinguishes statistical compatibility from practical importance: a small p-value alone would not establish that an effect is important to patients, while a non-small p-value does not prove the absence of an effect.

The primary endpoint used non-responder imputation. In general, this approach classifies missing response outcomes as failures to respond. It can preserve a conservative interpretation under some circumstances, but its consequences depend on why observations are missing and on whether the assumption is appropriate. The record specifies this approach for ACR20, but further missing-data procedures and sensitivity analyses are not reported in the registry record. Handling of missing values for the secondary outcomes is also not reported in the registry record.

For continuous secondary outcomes, the reported group summaries are least-squares means with standard errors. A least-squares mean is a model-based adjusted mean, while a standard error reflects the estimated uncertainty in that mean. The recalculated mean differences compare those posted summaries across groups. The registry does not list sponsor-reported analyses for these secondary endpoints. The standard deviations used in the recalculations were approximated from the reported standard errors, as indicated by the analysis notes; consequently, those recalculations are not equivalent to a complete individual-participant-data analysis.

General considerations for binary outcomes include the number of events and the total number evaluated. With relatively few responses, estimates can be imprecise, and small changes in event counts can matter. General methods may also need to account for clustering or over-dispersion when observations are more variable than a simple model assumes. The record does not report that such features were part of the primary analysis, so they should not be presumed.

What does the analysis population mean?

The primary endpoint population is described as the full analysis set, comprising patients in the randomized set to whom study treatment had been assigned. This definition gives the population label used for the outcome, but the registry record does not report further details such as exclusions from that set or the number with endpoint data available in each analysis.

How should the two treatment comparisons be viewed?

Each dose is compared separately with placebo. These are two related comparisons within one study, not independent replications. If several hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis addresses multiplicity. Whether the sponsor adjusted for multiple comparisons, and what testing hierarchy or decision rule was specified, is not reported in the registry record.

What do planning calculations express?

Planning illustrations estimate group sizes under stated assumptions for a hypothetical future comparison. They are not evidence about the probability that this completed study detected an effect. Their values depend on the assumed effect size and statistical model; smaller effects generally require more participants to detect reliably. The original trial's sample-size justification and design assumptions are not reported in the registry record.

11. Confidence Intervals and Precision

The primary response percentages are point estimates, and the confidence intervals communicate how uncertain the treatment contrasts are. The recalculated intervals for both secukinumab-versus-placebo risk differences extend across zero. Thus, the data are compatible with no difference as well as with effects in either direction over the ranges represented by those intervals. The intervals are not narrow enough to establish a precise magnitude from the unadjusted summaries alone.

The sponsor-reported logistic-regression odds ratio for AIN457 75 mg was 1.55, with a 95% confidence interval from 0.79 to 3.03. For AIN457 150mg, the odds ratio was 1.62, with a 95% confidence interval from 0.83 to 3.15. Each interval includes one, the no-odds-difference value. Their breadth indicates that the observed data are compatible with a range of possible odds contrasts; the point estimates should not be read without that uncertainty.

Precision is affected by the amount of information in the data, including the number of participants and the frequency of the outcome. In general, binary outcomes with limited event information can yield broad intervals. The enrolled study and analysis group sizes are modest compared with some of the hypothetical planning illustrations, but those illustrations are based on assumed effects and should not be treated as a direct test of this study's adequacy.

Confidence intervals address sampling uncertainty under a statistical model. They do not capture every source of uncertainty, including unreported protocol decisions, missing-data assumptions, or the consequences of examining multiple outcomes. Nor do they establish whether a difference, if present, would be important in practice. Interpretation therefore depends on the endpoint definition, the analysis method, and the broader clinical context, which is not fully described in the registry record.

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 planning illustrations express the number of participants per arm for the binary and continuous comparisons in this study. They do not express total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial's original sample-size assumptions and justification are not reported in the registry record.

For the primary ACR20 comparison of AIN457 75 mg with placebo, planning for 100% of the observed effect gives 321 participants per arm for 80% power and 428 participants per arm for 90% power. Planning for 75% gives 558 and 746 participants per arm, respectively; planning for 50% gives 1,227 and 1,642 participants per arm. For AIN457 150mg versus placebo, the corresponding figures are 279 and 373 for 100% of the observed effect, 486 and 649 for 75%, and 1,066 and 1,427 for 50%.

The 80% power column describes the planned chance of detecting the assumed effect under the stated model if that effect is real; the 90% column uses a higher target chance under the same general assumptions. Smaller effects require more participants because they are harder to distinguish from random variation. These values are planning illustrations based on observed estimates, not observed power and not a retrospective statement about whether the completed study succeeded. The original design may have used different assumptions; those details are not reported in the registry record.

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 = 0.272; treatment proportion p₁ = 0.375; average p̄ = 0.323.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6615 = 1.2965.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6574 = 0.5533.
4. n = (1.2965 + 0.5533)² / (0.1034)² = 320.1, rounded up to 321 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 <- 0.271604938271605                          # control proportion
p1 <- 0.375                          # 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(1770379)
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 = 321 (80% power), 428 (90% power)
 75% of observed effect: n per arm = 558 (80% power), 746 (90% power)
 50% of observed effect: n per arm = 1,227 (80% power), 1,642 (90% power)
power.prop.test: 320.1 
Simulated power at n = 321 per arm: 0.798 (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 sponsor-reported primary comparisons use logistic regression and report odds ratios with 95% confidence intervals. For AIN457 75 mg versus placebo, the reported odds ratio is 1.55 (95% CI 0.79 to 3.03); for AIN457 150mg versus placebo, it is 1.62 (95% CI 0.83 to 3.15). Both intervals include one, the null value for an odds ratio.

The recalculated comparisons use unadjusted risk differences derived from posted summary counts. That is a different effect scale and a simpler calculation than logistic regression, so numerical estimates need not match. The recalculated risk-difference intervals include zero, consistent with the sponsor intervals including the null on the odds-ratio scale. The recalculated unadjusted p-values are 0.161 for the 75 mg comparison and 0.132 for the 150mg comparison.

The record does not identify a discrepancy between the sponsor results and the recalculations. The sponsor's logistic-regression analyses remain the reported study analyses; summary-statistic recalculations provide context but cannot reproduce unreported model details or adjustments. Further information about covariates, model specification, or the sponsor's treatment of missing data beyond the stated non-responder imputation is not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The record identifies one primary endpoint and three secondary outcomes. It reports two treatment-versus-placebo comparisons for the primary endpoint and also posts comparisons for the secondary outcomes. Testing multiple endpoints or contrasts raises a general multiplicity concern: without an adjustment or a prespecified testing strategy, the chance of at least one apparently positive result can be greater than for a single planned test. The registry record does not report a multiplicity adjustment, testing hierarchy, or decision rule.

The primary outcome uses non-responder imputation at Week 24. This specifies that missing primary response status is counted as non-response. The record does not report the amount or reasons for missing primary data, whether additional sensitivity analyses were conducted, or how alternative assumptions might affect the result. Missing-data methods for the secondary endpoints are not reported in the registry record.

The primary analysis population is the full analysis set, defined as all patients from the randomized set to whom study treatment had been assigned. The record does not provide further details of exclusions, endpoint availability, or whether the reported analyses followed this population definition without exception. No interim analyses or stopping rules are reported in the registry record. The reason for the terminated status is also not reported, so the impact of termination on planned follow-up or analysis cannot be determined from the record.

These omissions do not invalidate the posted results, but they limit assessment of how closely the analyses followed a prespecified plan and how robust they are to alternate assumptions. Confidence intervals and p-values describe uncertainty within their analysis framework; they do not resolve uncertainty about unreported methods or missing observations.

16. 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: gastroenteritis (1.7%), rheumatoid arthritis (1.7%), atrial fibrillation (0.9%), acute vestibular syndrome (0.9%), impaired healing (0.9%).

The adverse-event record lists serious adverse events among groups titled Any AIN457 75 mg, Any AIN457 150 mg, and Placebo. The respective serious-event counts are 12 among 115 at risk, 9 among 115 at risk, and 0 among 79 at risk. The record also lists other adverse events in those groups: 77 among 115 at risk, 63 among 115 at risk, and 35 among 79 at risk. These safety denominators differ from the primary efficacy group sizes; the registry record does not explain the difference.

The listed serious-event terms with the largest reported percentages include gastroenteritis and rheumatoid arthritis, each at 1.7%, followed by atrial fibrillation, acute vestibular syndrome, impaired healing, and acute cholecystitis, each at 0.9%. The registry record does not report deaths in the posted safety fields. These counts and terms describe what was recorded; they do not establish that an event was caused by treatment, nor do they by themselves permit a complete comparison of safety between groups.

Interpretation is limited by the absence of further details about event definitions, exposure duration, event timing, severity, or attribution. The study is listed as terminated, but the reason is not reported in the registry record.

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

The primary result answers a specific question: what proportion of participants assigned to each group met the registry's ACR20 criteria at Week 24 under the stated non-responder-imputation approach? The observed percentages were higher in both secukinumab groups than in placebo. The uncertainty analyses are also important: the sponsor-reported odds-ratio intervals include one, and the unadjusted recalculated risk-difference intervals include zero. The posted data therefore do not provide a precise estimate of the treatment contrast from these summaries.

This result does not establish that a treatment works or does not work. It does not show that all participants experienced the same changes, because ACR20 compresses several measures into a responder classification. It does not describe outcomes beyond Week 24, even though the official title describes intended long-term assessment up to 5 years. Completion of that longer-term assessment is not reported in the registry record.

The results also do not establish the safety profile for all people with rheumatoid arthritis. Safety counts are presented for specified groups and risk sets, but details about exposure, event attribution, and follow-up are not reported. Nor can the findings automatically be generalized to people who differ from the study population, including those without the stated history of inadequate response or intolerance to anti-TNFα agents.

Clinical interpretation requires more than a comparison of percentages or a p-value. It depends on the size and precision of the estimated differences, the meaning of the response definition, the analysis population, missing-data assumptions, and the broader clinical context. The registry record supplies some of these elements but leaves others unreported. The findings are best understood as a time-specific account of the posted trial results, with uncertainty and reporting limitations kept in view.

18. Why This Trial Matters Statistically

This trial illustrates why a reported percentage should not be read in isolation. The ACR20 response proportions are higher in the two secukinumab groups than in placebo, but the uncertainty intervals for both the sponsor's odds ratios and the recalculated risk differences include their respective null values. The difference between a point estimate and the precision around it is central to statistical interpretation.

It also shows how analysis scale matters. Logistic regression reports odds ratios, while an unadjusted comparison of response proportions yields risk differences. These quantities describe related contrasts in different ways and are not interchangeable. Considering both can help readers understand the posted information, while recognizing that a summary-statistic recalculation does not replace the sponsor's model-based analysis.

The endpoint definition and missing-data rule are also consequential. ACR20 depends on joint counts and additional disease measures, and missing Week 24 response status was treated as non-response. Those details define what the result means and what assumptions underlie it. The three secondary outcomes add evidence across related domains but introduce multiplicity concerns that the registry record does not resolve.

Finally, the terminated status, lack of a reported reason, and limited detail about longer-term follow-up constrain interpretation. Statistical results are most useful when read alongside design, population, endpoint, analysis, precision, and reporting completeness. This record offers a practical example of how each element shapes what can responsibly be concluded from a clinical trial.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The study is listed as terminated, but the reason for termination is not reported in the registry record. The official title describes intended assessment up to 5 years, while the posted primary endpoint is at Week 24; completion and results of the longer-term assessment are not reported. This limits what can be inferred about durability or later outcomes.

The primary endpoint is a composite responder measure, and the record does not provide results for each component as part of the primary outcome. The endpoint therefore cannot show which components contributed most to the overall response classification. Week 24 missing response status was handled by non-responder imputation, but the amount and reasons for missingness and sensitivity analyses are not reported.

The sponsor-reported primary analyses use logistic regression, but model details beyond the method and odds ratios are not reported. The recalculations are unadjusted and based on posted summaries; they cannot account for covariates or other features of the original analysis. Secondary endpoints have recalculated comparisons but no sponsor-reported analyses in the record, and their missing-data methods and multiplicity handling are not reported.

The safety groups have risk sets that differ from the primary efficacy group sizes, without an explanation in the registry record. Event exposure time, attribution, and detailed follow-up are also not reported. The record does not provide the protocol's original sample-size justification, interim-analysis plan, or reasons for study termination. These limitations affect how fully the design and results can be assessed.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Secukinumab Efficacy and Safety Study in Patients With Rheumatoid Arthritis and Inadequate Response to Anti-TNFα Agents. — NCT01770379.
• Registry record last updated 2016-07-21; status last verified 2016-06.
• Results first posted 2016-07-21.
• 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

NCT01770379 is a terminated Phase III randomized, double-blind, placebo-controlled, parallel-group study of subcutaneous secukinumab in patients with active rheumatoid arthritis who had an inadequate response to anti-TNFα agents. The record lists Novartis Pharmaceuticals as sponsor and enrollment as 242. The study began in 2012-10, with primary completion in 2015-05.

The primary endpoint was Week 24 ACR20 response, analyzed in the full analysis set with non-responder imputation. Posted response percentages were 37.5% for AIN457 75 mg, 38.3% for AIN457 150mg, and 27.2% for placebo. Sponsor-reported logistic-regression confidence intervals and unadjusted recalculated risk-difference intervals include their respective null values.

Three secondary outcomes and adverse-event counts are also reported. The reason for termination, multiplicity plan, original sample-size justification, and details of longer-term follow-up are not reported in the registry record.