Controlled Study of Humira in Subjects With Chronic Plaque Psoriasis of the Hands and/or Feet: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Controlled Study of Humira in Subjects With Chronic Plaque Psoriasis of the Hands and/or Feet (NCT00735787), a randomized phase 4 study. The primary outcome is Number of Subjects With Physician's Global Assessment of Psoriasis (PGA) of Clear or Almost Clear at Week 16.

2. Clinical Question

The study asked whether participants assigned to adalimumab or placebo differed in the number who reached a specified physician-assessed psoriasis status at Week 16. The registry describes an adult population with chronic plaque psoriasis affecting the hands and/or feet. It reports the Week 16 outcome for the intention-to-treat population, with missing Week 16 assessments treated as non-responses.

The primary endpoint is a threshold outcome rather than a measure of average change. It counts participants whose physician assessment met either of the two specified categories. The posted results report 15 participants in the adalimumab group and 1 in the placebo/adalimumab group reaching that threshold at Week 16. These are observed group counts; the registry’s missing-assessment rule classifies participants without a Week 16 assessment as non-responders.

The question is therefore about the Week 16 comparison during the initial randomized treatment period. It is not a comparison of the later open-label period, and it does not by itself describe longer-term response or outcomes beyond the stated assessment time.

3. Trial Design

The registry describes a completed, Phase 4, randomized, double-masked, parallel-group study. The condition listed is psoriasis. Enrollment is recorded as 81. The study began in 2008-08, and primary completion is recorded as 2009-09. The registry’s stated aim was to evaluate efficacy and safety during a 16-week course of Humira (adalimumab) compared with placebo in adults with chronic plaque psoriasis of the hands and/or feet, as well as the sustainability of response for 12 additional weeks.

For the initial period, the placebo/adalimumab group received placebo injections at Week 0 and every other week from Week 1 through Week 15. The adalimumab group received an 80 mg loading dose at Week 0 and 40 mg every other week from Weeks 1 through 15. The reported primary endpoint is assessed at Week 16. The group labels in the results preserve the initial placebo assignment while also indicating later treatment: participants who continued in the study received open-label adalimumab during the second period.

In that second period, the registry describes an 80 mg adalimumab dose at Week 16 followed by open-label 40 mg every other week from Week 17 to Week 27 for participants continuing from the placebo group. Participants initially assigned adalimumab received placebo injections at Week 16 to maintain masking, followed by open-label adalimumab from Week 17. The end of that latter schedule is incomplete in the registry description, so its full timing is not reported in the registry record.

The primary comparison is the randomized Week 16 comparison, not a comparison of the later open-label treatment period. The record gives group sizes of 23 for placebo/adalimumab and 49 for adalimumab in the primary results. The reason these analysis group sizes differ from the enrollment figure is not reported in the registry record. Further details about the randomization procedure, allocation concealment, or how masking was implemented 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.

Period 1

Period 2

Analysis population for the primary outcome, as defined in the registry: Analysis was based on the intention to treat (ITT) subject population. Subjects who did not achieve PGA assessments at Week 16 were imputed as non-responders.

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Physician's Global Assessment of Psoriasis (PGA) of Clear or Almost Clear at Week 16, measured over Week 16.

The primary endpoint counts participants whose physician’s Global Assessment of Psoriasis (PGA) was clear or almost clear at Week 16. The registry defines clear as representing no signs of plaque psoriasis and almost clear as representing just perceptible erythema and scaling. The PGA is described as a five-point scale used to assess disease severity at the physician’s evaluation: 0 is clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 is severe.

Turning the scale into a threshold outcome focuses the comparison on whether a participant reached one of the two most favorable categories specified for this endpoint. It is a binary outcome for analysis: each participant either meets the clear-or-almost-clear definition or does not. The posted endpoint is a count of participants, rather than a mean score or a change from baseline.

This type of endpoint is useful when the clinical question is framed around reaching a defined status, and when a count of participants meeting that status is easier to interpret than an average across scale values. It also discards distinctions within each side of the threshold: the endpoint does not distinguish clear from almost clear, and it does not describe the distribution among participants who did not meet the threshold. The registry’s analysis population is intention to treat, with participants lacking a Week 16 PGA assessment imputed as non-responders. The endpoint therefore reflects the stated threshold and the stated handling of missing assessments, not a complete description of every participant’s disease severity.

7. Results Posted in the Registry

• Adalimumab: 30.6% (15/49) versus 4.3% (1/23) on control; risk difference 26.3 percentage points (95% CI 10.9 to 41.6), risk ratio 7.04 (0.99–50.12); unadjusted two-proportion z-test p = 0.012.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary because it records whether a participant did or did not achieve clear or almost clear PGA status at Week 16. For a binary endpoint, the group proportion is the number meeting the definition relative to the number analyzed in that group. The posted proportions are 0.306 for adalimumab and 0.043 for placebo/adalimumab. The registry also gives the underlying counts and analysis group sizes: 15 of 49 and 1 of 23.

What does a risk difference describe?

A risk difference subtracts one group’s event proportion from the other group’s event proportion. It is an absolute measure, expressed on the same proportion scale as the outcome. The recalculated unadjusted risk difference is 0.263, with a 95% confidence interval from 0.109 to 0.416. The estimate describes the observed separation between the groups under this calculation. It is not an adjusted estimate, and it should not be confused with a relative measure such as a risk ratio or odds ratio.

Relative measures compare the groups by division rather than subtraction. The record includes a risk ratio estimate of 7.041 with interval limits 0.989 and 50.12, and an odds ratio estimate of 9.706 with interval limits 1.196 and 78.79. Such measures can look large when the control-group event proportion is small, and their interpretation differs from an absolute risk difference. They do not replace the underlying group counts or describe how many participants met the endpoint.

What does a confidence interval add?

A confidence interval conveys the uncertainty associated with an estimate under the assumptions of the method used to construct it. It shows a range of values compatible with the data and method at the stated confidence level; it is not a guarantee that the true effect lies in that particular interval. A narrower interval indicates greater statistical precision than a wider one, while the interval’s location indicates which values are compatible with the data. The risk-difference interval is entirely above zero, but its width shows that the effect is not pinned down to a single value.

Why are there two p-values?

The posted unadjusted recalculation gives p = 0.012. The registry also reports a Fisher exact analysis with p = 0.014. Fisher’s exact test is a method for comparing categorical outcomes between groups, particularly useful when counts are sparse. It evaluates how compatible the observed allocation of outcomes is with a null hypothesis of no association, given the margins of the comparison. A p-value is not the probability that a result occurred by chance, nor does it measure the probability that one treatment is better. The sponsor’s own result is the registry-reported Fisher exact p-value; the recalculated result is a separate unadjusted analysis.

The p-values are close but are not identical because they arise from distinct analysis procedures. The registry record does not give enough information to reconstruct every step of the sponsor’s analysis beyond identifying Fisher Exact and reporting its p-value. The unadjusted comparison does not incorporate adjustment for any other outcomes, covariates, or design features.

How does missing-outcome handling matter?

The registry says the primary analysis used the intention-to-treat population and classified participants without a Week 16 PGA assessment as non-responders. Intention-to-treat analysis generally aims to retain participants in the groups to which they were assigned, preserving the randomized comparison. Counting missing assessments as non-responses is a particular imputation rule: it assigns an outcome category instead of excluding those participants from the endpoint analysis. This can affect group counts and proportions, especially if missingness differs between groups. The record does not state the number of missing Week 16 assessments or report sensitivity analyses using alternative assumptions.

What can the methods establish?

These methods quantify the observed Week 16 difference and its statistical uncertainty under the stated analysis. Random allocation supports a comparison between assigned groups, but the registry entries available do not fully describe the randomization process, masking implementation, or all analytic decisions. Statistical significance does not establish the size, durability, or broader relevance of the result. It also does not answer questions about outcomes beyond the defined PGA threshold or the later open-label period. Those questions require other reported analyses and sufficient detail about their methods.

The registry lists 20 outcome measures and 1 analysis in the record, with 19 secondary outcomes posted. A multiplicity adjustment or an analysis plan controlling the interpretation across outcomes is not reported in the registry record. A single primary comparison can be interpreted as the stated endpoint analysis, but it should not be assumed that the broader family of outcomes was handled with a particular correction. The record also does not report whether interim analyses were conducted.

10. Confidence Intervals and Precision

The primary recalculated risk difference is 0.263, and its 95% confidence interval extends from 0.109 to 0.416. The interval gives a range of values compatible with the observed data under the calculation used. Because the interval does not include zero, the estimated difference is positive across the interval’s reported limits. This does not eliminate uncertainty: the interval still spans a range of possible effect sizes, and the point estimate should not be treated as exact.

The observed counts are 15 of 49 in the adalimumab group and 1 of 23 in the placebo/adalimumab group. The relatively small number of participants meeting the endpoint in the comparator group is relevant to precision: with limited outcome information, estimates can be sensitive to a small number of observations. This is a general statistical consideration, not evidence that any particular observation is incorrect.

The record also reports a risk ratio and odds ratio with broad interval limits. Relative measures can be especially uncertain when one group has few events, and their intervals should be read as part of the evidence rather than as precise single values. The risk-difference interval may be more directly interpretable for the absolute separation in proportions, while the relative measures answer different questions.

The sponsor-reported Fisher exact p-value is 0.014, while the unadjusted recalculation gives p = 0.012. Neither p-value describes precision as directly as the confidence interval. Precision depends on the amount of information and the variability in the data; a statistically significant p-value does not make an estimate precise. The registry does not report a confidence interval for the sponsor’s Fisher exact result, so the reported risk-difference interval should not be attributed to that sponsor analysis.

These intervals describe uncertainty for the recorded Week 16 endpoint and analysis, not uncertainty about every secondary outcome or later-period response. Further context about missing assessments and analysis choices would help evaluate how robust the estimate is to alternative assumptions, but that information is not reported in the registry record.

11. 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 figures are participants per arm, not total events. For planning to detect 100% of the observed effect, the illustration gives 32 participants per arm for 80% power and 42 participants per arm for 90% power. For 75% of the observed effect, it gives 49 participants per arm for 80% power and 64 participants per arm for 90% power. For 50% of the observed effect, it gives 88 participants per arm for 80% power and 117 participants per arm for 90% power.

Power is the probability, under a specified statistical model and assumed effect, of detecting an effect at the chosen significance level if that effect is present. The 80% column represents a design targeting an 80% chance of detecting the stated effect under the planning assumptions; the 90% column targets a 90% chance. A larger target power generally requires more participants for the same assumed effect. Likewise, planning for a smaller effect requires more participants, because smaller differences are harder to distinguish from random variation.

The illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumed effect is the stated fraction of the observed effect. These are planning assumptions for an illustration based on the observed result, not the trial’s original design assumptions. The original sample-size justification and assumptions are not reported in the registry record. These figures are not observed power; they describe hypothetical planning under the listed assumptions, not the probability that this completed trial detected its result.

12. 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 = 0.043; treatment proportion p₁ = 0.306; average p̄ = 0.175.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5371 = 1.0527.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5040 = 0.4242.
4. n = (1.0527 + 0.4242)² / (0.2626)² = 31.6, rounded up to 32 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 <- 0.0434782608695652                          # control proportion
p1 <- 0.306122448979592                          # 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(735787)
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 = 32 (80% power), 42 (90% power)
 75% of observed effect: n per arm = 49 (80% power), 64 (90% power)
 50% of observed effect: n per arm = 88 (80% power), 117 (90% power)
power.prop.test: 31.6 
Simulated power at n = 32 per arm: 0.858 (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.

13. Analyses Reported by the Sponsor

The registry reports the sponsor’s own primary comparison as a Fisher Exact analysis with p = 0.014. That is the reported sponsor result and should be distinguished from the unadjusted recalculation, which gives p = 0.012 and a risk difference of 0.263 with a 95% confidence interval from 0.109 to 0.416. The recalculation is a simple unadjusted comparison from the posted group summaries; it is not a replacement for the sponsor’s analysis.

The two p-values are close, but they are not identical. The registry identifies the sponsor’s method as Fisher Exact, while the recalculated result is an unadjusted analysis. The record does not provide additional detail sufficient to recreate all sponsor analysis steps or to attach the recalculated confidence interval to the sponsor’s test. The registry does not indicate a discrepancy between the sponsor result and the recalculation.

Both results concern the same Week 16 binary PGA threshold, but they should be presented with their method labels intact. The sponsor’s p-value is the registry-reported analysis; the recalculated estimate and interval offer a separate description of the posted counts and their uncertainty. Neither result should be interpreted as a measure of clinical importance or as proof of an outcome beyond this endpoint and assessment time.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures, including the primary Week 16 PGA endpoint and 19 secondary outcomes posted. The secondary outcomes include mean changes in ESIF overall and for palms and soles, counts with moderate or marked ESIF improvement, mean change in NAPSI, and counts meeting other PGA thresholds. These outcomes address related but distinct aspects of psoriasis assessment.

When many outcomes are tested, the chance of observing one or more apparently small p-values can increase, even if no effect exists across the full set. Statistical approaches to multiplicity can control how results are interpreted across a family of tests. The registry record does not report a multiplicity adjustment, a hierarchy of testing, or another plan for controlling interpretation across the outcome set. It should not be assumed that a correction was or was not used beyond what the record states.

The primary endpoint analysis is reported as an intention-to-treat analysis. Participants without a Week 16 PGA assessment were imputed as non-responders. This is an explicit missing-data rule, but the number of participants with missing assessments is not reported in the registry record. The record does not describe sensitivity analyses, alternative imputation methods, or the reasons assessments might have been missing. As a result, the impact of the missing-data rule cannot be assessed from the record alone.

The registry reports one analysis for the primary comparison and identifies the sponsor’s method as Fisher Exact. The record does not report whether interim analyses occurred or provide a fuller statistical analysis plan. It also does not report additional details about covariate adjustment, stratification, or prespecified handling of protocol deviations. These omissions do not change the posted counts, but they limit independent assessment of the analysis process.

Analysis populations matter because results can differ depending on which participants and outcomes are included. The stated intention-to-treat population and non-responder imputation rule define the reported endpoint analysis at a high level. The registry does not provide enough detail to establish whether other populations were analyzed or to compare their results. Interpretation should therefore stay with the population and handling rule explicitly reported.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: breast cancer (4.3%), breast mass (4.3%), acute myocardial infarction (2.0%), gastrointestinal haemorrhage (2.0%).

The registry records serious adverse events affecting 1 of 23 participants in the placebo/adalimumab group and 2 of 49 in the adalimumab group. Other adverse events are recorded for 15 of 23 and 30 of 49 participants, respectively. These are descriptive counts from the posted safety information; they are not adjusted comparisons and do not by themselves establish that one group had greater or lesser risk.

The record lists Breast cancer at 4.3%, Breast mass at 4.3%, Acute myocardial infarction at 2.0%, and Gastrointestinal haemorrhage at 2.0% among the top serious adverse-event terms. The registry does not assign these listed terms to specific treatment groups in the record, so the percentages should not be read as group-specific estimates. The record does not report deaths.

Safety counts depend on the period covered, definitions, and how events are attributed and collected. Those details are not fully described in the registry record for these figures. The initial comparison also transitions to open-label adalimumab for participants continuing into the second period, so the Week 16 randomized comparison should be kept distinct from later follow-up. The reported counts are not a complete account of an individual participant’s risks and do not support medical advice.

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

The posted Week 16 data show that 15 participants in the adalimumab group and 1 participant in the placebo/adalimumab group met the defined PGA threshold of clear or almost clear. The unadjusted risk difference is 0.263, with a 95% confidence interval from 0.109 to 0.416. The sponsor-reported Fisher exact analysis gives p = 0.014, and the unadjusted recalculation gives p = 0.012. Together, these statistics describe the direction and uncertainty of the observed group comparison for this endpoint.

The result does not mean that every participant assigned adalimumab met the threshold, nor does it describe the full distribution of disease severity. The binary endpoint combines clear and almost clear, and it places all other PGA categories on the non-response side of the threshold. It therefore cannot show whether participants below the threshold had mild, moderate, or severe status, or the degree of change each participant experienced from baseline.

The result is specific to the randomized Week 16 comparison in adults with chronic plaque psoriasis of the hands and/or feet. It does not establish the sustainability of response through the additional 12 weeks described in the study aim, because the primary endpoint presented is at Week 16 and later treatment was open-label. It also does not resolve the outcomes of the secondary measures or provide a broader account of safety.

Statistical evidence is not the same as a clinical decision. The p-value does not quantify treatment benefit, and the confidence interval does not state the probability that a particular value is true. The findings should be understood as a comparison of observed counts under the registry’s stated analysis, including its rule that missing Week 16 assessments were treated as non-responses. The record’s incomplete reporting of some design, analysis, missing-data, and multiplicity details constrains further interpretation.

17. Why This Trial Matters Statistically

This trial illustrates why a binary clinical endpoint needs both its definition and its counts to be interpreted correctly. The primary outcome is not simply a general improvement measure: it is the number of participants classified as clear or almost clear on a physician assessment at Week 16. The scale categories and threshold determine which observations count as successes, so the endpoint definition is central to understanding the estimate.

It also shows the value of reporting an absolute effect with uncertainty. The risk difference of 0.263 summarizes the observed separation in proportions, while its 95% confidence interval, from 0.109 to 0.416, conveys that the estimate is not exact. The group counts make the underlying evidence transparent, particularly when the number meeting the endpoint is limited in one group.

The record places two analyses side by side in interpretation: a sponsor-reported Fisher exact p-value of 0.014 and an unadjusted recalculation with p = 0.012. They are close, but statistical reporting benefits from preserving the distinction between a sponsor analysis and a simple recalculation rather than treating them as interchangeable. This is a useful general lesson in registry-based assessment.

Finally, the record demonstrates why missing-data rules, multiplicity, and trial design assumptions matter. The non-responder imputation rule is stated, while the number of missing assessments and the plan for interpreting multiple outcomes are not reported. The planning illustration is also distinct from the original design rationale. Recognizing these differences helps keep the interpretation tied to what the analysis can support.

18. 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 results include unequal analysis group sizes: 23 participants in the placebo/adalimumab group and 49 in the adalimumab group. Enrollment is recorded as 81, but the reason for the difference between enrollment and the endpoint analysis group sizes is not reported in the registry record. The record does not state whether this reflects exclusions, missing data, or another aspect of the analysis population, so no explanation should be inferred.

The primary endpoint is a threshold-based PGA measure at Week 16. While the registry defines the categories, a binary count does not retain all information in the five-point scale. It does not show changes from baseline for each participant or distinguish clear from almost clear in the reported count. Other outcomes are listed, but their detailed results are not part of the primary comparison.

Missing Week 16 assessments were imputed as non-responses. The number of missing assessments and any sensitivity analysis under alternative assumptions are not reported in the registry record. The effect of this rule on the group estimates therefore cannot be evaluated from the recorded information. A multiplicity plan for the primary and secondary outcomes is also not reported.

The record provides limited detail about how randomization and masking were conducted, and the original sample-size justification is not reported. The sponsor-reported analysis is identified as Fisher Exact, but further analytic details are not available in the registry record. The sample-size illustration based on the observed effect should not be mistaken for the study’s original design rationale.

Finally, the later study period involved open-label adalimumab for participants continuing in the study. The primary comparison at Week 16 remains the randomized comparison, but it does not answer questions about the later period. The registry’s description of the open-label schedule for the initial adalimumab group is incomplete, and the listed serious adverse-event terms are not assigned to treatment groups in the record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Controlled Study of Humira in Subjects With Chronic Plaque Psoriasis of the Hands and/or Feet — NCT00735787.
• Registry record last updated 2010-11-01; status last verified 2010-10.
• Results first posted 2010-11-01.
• 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.

22. Record Summary

This completed Phase 4 study was randomized, double-masked, and parallel-group. It evaluated adalimumab against placebo in adults with chronic plaque psoriasis of the hands and/or feet. Enrollment is recorded as 81, with study start in 2008-08 and primary completion in 2009-09.

The primary endpoint counted participants with a PGA rating of clear or almost clear at Week 16. The posted counts were 15 of 49 in the adalimumab group and 1 of 23 in the placebo/adalimumab group. The unadjusted risk difference was 0.263, with a 95% confidence interval from 0.109 to 0.416. The sponsor-reported Fisher exact p-value was 0.014.

The primary analysis used the intention-to-treat population and treated missing Week 16 PGA assessments as non-responses. Details about the number missing, multiplicity handling, and the original sample-size rationale are not reported in the registry record. Safety information is recorded descriptively and should be interpreted separately from the efficacy comparison.