Safety and Efficacy of Adalimumab (Humira) for Hidradenitis Suppurativa (HS) Peri-Surgically: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Adalimumab (Humira) for Hidradenitis Suppurativa (HS) Peri-Surgically (NCT02808975), a randomized phase 4 study. The primary outcome is Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12.

2. Clinical Question

The clinical question concerns adalimumab used around surgery, rather than adalimumab in isolation from the surgical context. The study objective was to assess safety and efficacy of adalimumab prior to surgery among participants with moderate to severe HS who were surgical candidates. The registry record does not specify in the primary endpoint description how surgery was timed in relation to the Week 12 assessment, nor does it provide a more detailed account of the surgical procedures. Those details are not reported in the registry record.

3. Trial Design

This was a phase 4, randomized, parallel-group, placebo-controlled study sponsored by AbbVie. The registry record describes the study as double-blind in its official title and lists quadruple masking in its design fields. It was multicenter. Enrollment was 206, with 103 participants listed in each primary endpoint arm. The study status is completed.

The registry dates the study start to 2016-07-18 and primary completion to 2019-05-16. Participants were assigned to placebo or adalimumab. Both arms had subcutaneous injections across the listed periods: Period A, Period B and Period C. In the adalimumab arm, the listed injections were 40 mg; the placebo arm description does not specify a dose. The registry does not report the randomization procedure or the reasons for the masking level beyond its design classification.

The primary endpoint was the percentage achieving HiSCR at Week 12, assessed in the intent-to-treat population, defined in the record as all participants randomized at the baseline visit. Non-responder imputation was used for missing data for this endpoint. Four secondary outcomes are listed: HiSCR-es at Week 12, HiSCR-es at Week 24, change in surgical-site surface area from baseline to Week 12, and the percentage at Week 12 requiring less extensive surgery than planned at baseline or no surgery. Results are posted for three of those secondary outcomes; numerical results for change in surgical-site surface area are not reported in the registry record.

The registry record does not report the original sample-size justification, the trial’s planned significance level, or the statistical analysis plan in sufficient detail to establish all planned analyses. Interim analyses and any stopping rules are not reported in the registry record. Those omissions limit how fully the posted results can be compared with the study’s original protocol.

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: Intent-to-Treat (ITT) population: all participants who were randomized at the Baseline visit

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) population: all participants who were randomized at the Baseline visit; non-responder imputation (NRI) was used for missing data

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.

Population: Intent-to-Treat (ITT) population: all participants who were randomized at the Baseline visit

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12, measured over At Week 12.

The primary endpoint was the percentage of participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12. The registry defines a response as at least a 50% reduction in abscess and inflammatory nodule (AN) count relative to baseline, without an increase in abscess count or draining fistula count. This combines improvement in inflammatory lesions with a condition that the specified counts do not worsen.

A percentage endpoint expresses how many participants in each arm met the response definition, rather than the average change in an individual measurement. The primary endpoint uses the intent-to-treat population: all participants randomized at the baseline visit. For missing primary endpoint data, the registry states that non-responder imputation (NRI) was used. Under this approach, participants with missing outcome data are treated as not having achieved the endpoint for the analysis. This can affect the estimated response percentages, so the result should be understood in light of that stated missing-data rule.

A binary response endpoint is useful for presenting the proportion meeting a defined clinical criterion, but it does not show the full distribution of changes in lesion counts. It also does not, by itself, describe surgical outcomes or establish how responses relate to the timing or details of surgery. Those are distinct questions. The record lists additional surgical and response outcomes, but the numerical result for change in surgical-site surface area is not reported in the registry record.

HiSCR-es is named among the secondary outcomes, but its definition is not reported in the registry record. It should therefore not be assumed to be identical to the primary HiSCR definition.

7. Results Posted in the Registry

• Adalimumab: 47.6% (49/103) versus 34.0% (35/103) on control; risk difference 13.6 percentage points (95% CI 0.3 to 26.9), risk ratio 1.40 (1.00–1.96); unadjusted two-proportion z-test p = 0.047.

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.

Percentage of Participants Achieving HiSCR-es at Week 12

• 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:
  • Adalimumab: 47.6% (49/103) versus 35.0% (36/103) on control; risk difference 12.6 percentage points (95% CI -0.7 to 26.0), risk ratio 1.36 (0.98–1.90); unadjusted two-proportion z-test p = 0.066.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Adalimumab and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants Achieving HiSCR-es at Week 24

• 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:
  • Adalimumab: 51.5% (53/103) versus 31.1% (32/103) on control; risk difference 20.4 percentage points (95% CI 7.2 to 33.5), risk ratio 1.66 (1.17–2.33); unadjusted two-proportion z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Adalimumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants at Week 12 That Require a Less Extensive Surgery Than the Surgical Plan (Determined at Baseline) or No Surgery

• 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:
  • Adalimumab: 46.3% (38/82) versus 43.7% (38/87) on control; risk difference 2.7 percentage points (95% CI -12.3 to 17.7), risk ratio 1.06 (0.76–1.48); unadjusted two-proportion z-test p = 0.728.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Adalimumab and the control. The interval gives the range of effects that remain compatible with the data.

Across the posted secondary results, the response outcomes show a generally higher observed response proportion in the adalimumab arm than in the placebo arm. The Week 24 response comparison has a confidence interval for the difference that does not include zero, whereas the Week 12 HiSCR-es comparison has an interval that includes zero. The surgery-related outcome, which concerns less extensive surgery than planned at baseline or no surgery, has a comparatively uncertain difference whose interval also includes zero. These are distinct outcomes and should not be treated as interchangeable confirmations of the primary endpoint.

The broad pattern is consistent with the direction of the primary Week 12 HiSCR comparison, but it does not mean every secondary endpoint gives equally clear evidence. The secondary outcomes address different time points, a separately named response measure, and a surgical-plan outcome. The registry does not report the definition of HiSCR-es, and numerical results for change in surgical-site surface area from baseline to Week 12 are not reported in the registry record.

Secondary comparisons generally carry less inferential weight when the testing plan and adjustment for multiple comparisons are not available. When several outcomes are examined, the chance of observing a small p-value somewhere among them can increase, depending on how the tests are related and how they are selected. The registry lists five outcome measures and five analyses, but adjustment for multiplicity is not reported in the registry record. The secondary findings are therefore useful for describing the pattern of posted outcomes, but should not be read as independent, definitive tests of the primary question.

The primary endpoint remains the prespecified focus identified by the registry as primary. Secondary results can add context about response over time and surgery-related outcomes, yet the missing analysis-plan details and unavailable surgical-site-area result limit a unified interpretation across all registered questions.

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

• Percentage of Participants Achieving HiSCR-es at Week 12
• Percentage of Participants Achieving HiSCR-es at Week 24
• Percent Change in the Surface Area of the Hidradenitis Suppurativa (HS) Surgical Site From Baseline to Week 12
• Percentage of Participants at Week 12 That Require a Less Extensive Surgery Than the Surgical Plan (Determined at Baseline) or No Surgery

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each participant either met the stated HiSCR response definition at Week 12 or did not. The endpoint is reported as a percentage, and the posted comparison expresses the between-arm contrast as a risk difference. A risk difference subtracts the response proportion in one group from that in the other; a value of zero represents equal proportions. The recalculated estimate is 0.136, with a confidence interval from 0.003 to 0.269.

What does the confidence interval describe?

A confidence interval gives a range of values compatible with the observed data under the method used to construct it. In repeated applications of a procedure with the same coverage properties, intervals built in that way would contain the target quantity at the stated rate. It is not a range containing a specified percentage of individual participants, and it does not mean there is a 95% probability that this particular interval contains the true value. The registry gives 95% confidence intervals for the arm-level percentages and the recalculated comparison.

The primary arm-level intervals are 24.8 to 43.1 for placebo and 37.9 to 57.2 for adalimumab. The comparative interval is more directly relevant to the difference between response proportions. Because it is an interval for a contrast, its position relative to zero is useful for assessing whether the data are compatible with no difference under the interval method. The interval’s width also signals uncertainty about the magnitude, even when the point estimate is positive.

How should the p-values be read?

A p-value is calculated under a null model, usually one that assumes no difference for the comparison being tested. It describes the probability of observing a result at least as extreme as the one obtained if that null model and the test assumptions hold. It is not the probability that the observed result arose by chance, and it does not indicate the probability that adalimumab is effective or ineffective. The primary recalculation reports p = 0.047; the registry’s Cochran-Mantel-Haenszel analysis reports p = 0.049. These are close, but they come from distinct analyses.

The registry identifies Cochran-Mantel-Haenszel as the sponsor’s primary comparison method. In general, this method can assess an association between treatment group and a categorical outcome across strata. The registry does not identify the strata used for this analysis, so no particular stratification scheme can be inferred. The recalculation is an unadjusted comparison based on the posted summary statistics; it should not be mistaken for the sponsor’s analysis.

Why can unadjusted and reported analyses differ?

Analyses can differ because they use different methods, assumptions, or adjustments. A method that accounts for strata may not produce exactly the same estimate or p-value as a simple unadjusted comparison. Here the recalculated p-value and the registry-reported p-value are close, and the record does not flag a discrepancy. The registry does not report enough detail to explain the precise difference between them or to reproduce the sponsor’s analysis fully.

What does non-responder imputation do?

The primary endpoint population is all participants randomized at baseline, and the registry states that NRI was used for missing primary endpoint data. In general, NRI treats a missing response assessment as a failure to meet the response definition. This preserves participants in the randomized analysis while applying a specific assumption to missing outcomes. Its impact depends on how much outcome data are missing and on the reasons for missingness; the amount and reasons for missing primary outcome data are not reported in the registry record.

Missing-data methods embody assumptions rather than recovering an unobserved outcome with certainty. NRI can be conservative in some circumstances, but it is not guaranteed to bias an estimate in a particular direction in every setting. The registry’s stated rule should therefore be reported as part of the endpoint definition, not as proof that missingness had no effect.

Why can over-dispersion matter?

General statistical context: over-dispersion occurs when variability in the data exceeds what a chosen model expects. It can make standard errors too small and confidence intervals too narrow if the model does not account for it. This is especially relevant to outcomes whose variability is modeled rather than directly represented by a simple binary proportion. The posted primary outcome is binary, and the registry does not report an over-dispersion assessment or a model specification beyond naming the Cochran-Mantel-Haenszel method.

What is not established by the method description?

The analysis method does not, on its own, establish that all model assumptions were met, that all registered analyses were prespecified, or that multiplicity was controlled. The detailed analysis plan, stratification factors, and adjustment for multiple comparisons are not reported in the registry record. The posted result supports a description of the specified comparison, while those missing details constrain stronger claims about the broader inferential plan.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data locate an estimated quantity. For the primary outcome, the placebo response estimate is 34.0%, with a 95% confidence interval from 24.8 to 43.1. The adalimumab response estimate is 47.6%, with a 95% confidence interval from 37.9 to 57.2. These intervals show uncertainty around each arm’s response proportion; they are not predictions for individual participants.

The recalculated risk difference is 0.136, with a 95% confidence interval from 0.003 to 0.269. The lower endpoint is close to zero, while the interval also allows a considerably larger positive difference. This means that the observed direction is positive, but the registry data do not pin down the magnitude very narrowly. The comparison interval is more informative about the between-arm difference than judging overlap or non-overlap of the separate arm intervals.

Confidence intervals depend on the method and assumptions used to construct them. The arm-level intervals and the recalculated comparative interval describe different quantities. The registry-reported Cochran-Mantel-Haenszel analysis gives p = 0.049, but does not report a comparative estimate or confidence interval for that analysis. The reported p-value alone does not provide the same information about the range of plausible effect sizes.

Precision is also affected by the number of observations and the outcome frequency, among other features. There were 103 participants in each primary arm, and the primary analysis used NRI for missing data. The number and pattern of missing assessments are not reported in the registry record, so their contribution to precision cannot be assessed from the record. The interval should be read as uncertainty under the stated analysis, not as protection against unreported design or data limitations.

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 figures are planning illustrations based on the observed effect, not the trial’s original design justification. For this binary outcome, the figures are participants per arm, not total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect.

The 80% power column gives the planned number of participants per arm for a design with an 80% chance of detecting the specified effect under the planning assumptions, if that effect and the assumptions were correct. The 90% power column gives the per-arm figure for a design with a 90% chance under the same conditions. Power is a property of a planned study under specified assumptions; it is not the probability that the observed finding is true.

The rows consider planning for 100%, 75% and 50% of the observed effect. The figures increase as the target effect becomes smaller: a study generally needs more participants to distinguish a smaller difference from background variation. For example, planning for 75% of the observed effect requires 359 participants per arm for 80% power and 480 per arm for 90% power. Planning for 50% of the observed effect requires 795 per arm for 80% power and 1,063 per arm for 90% power. These are illustrative calculations, not observed enrollment targets from the original protocol.

This is not observed power. The trial’s original sample-size assumptions, including its intended effect size and planned power, are not reported in the registry record. The illustration is conditional on the observed effect and stated calculation assumptions, and should not be read as evidence that the completed trial was adequately or inadequately powered.

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 = 0.340; treatment proportion p₁ = 0.476; average p̄ = 0.408.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6950 = 1.3621.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6883 = 0.5793.
4. n = (1.3621 + 0.5793)² / (0.1359)² = 204.0, rounded up to 205 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 <- 0.339805825242718                          # control proportion
p1 <- 0.475728155339806                          # 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(2808975)
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 = 205 (80% power), 273 (90% power)
 75% of observed effect: n per arm = 359 (80% power), 480 (90% power)
 50% of observed effect: n per arm = 795 (80% power), 1,063 (90% power)
power.prop.test: 204 
Simulated power at n = 205 per arm: 0.804 (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 reports a Cochran-Mantel-Haenszel superiority analysis for the primary comparison, with p = 0.049. The recalculation from the posted summary statistics is an unadjusted risk-difference analysis: the estimate is 0.136, its 95% confidence interval is 0.003 to 0.269, and p = 0.047. The two p-values are close, but they are not interchangeable because the methods differ.

The registry record does not provide the sponsor analysis’s comparative estimate or confidence interval, so the recalculation adds an unadjusted effect estimate and interval rather than reproducing every reported analysis statistic. The Cochran-Mantel-Haenszel result is the sponsor’s own analysis and should be treated as the primary reported inferential result. The recalculation is a supplementary check based on the posted arm summaries, not a substitute for the sponsor’s method.

The record marks the comparison as having no discrepancy. That means the posted information does not identify a conflict requiring resolution between the recalculation and the registry analysis. The small difference between the p-values is consistent with analyses that are close but not identical. The strata and other implementation details for the sponsor analysis are not reported in the registry record, so the precise source of the difference cannot be determined from the record.

15. Multiplicity, Missing Data and Analysis Populations

The primary analysis population is clearly described: the intent-to-treat population includes all participants randomized at the baseline visit, and non-responder imputation was used for missing primary endpoint data. This makes the primary result interpretable as a randomized-group comparison under the stated missing-data rule. However, the registry does not report the number of missing primary assessments or the reasons for missingness, so the consequences of the imputation cannot be evaluated from the posted record.

The analysis populations for the secondary outcomes are not fully described. The surgery-related endpoint lists 87 participants in the placebo arm and 82 in the adalimumab arm, while the primary outcome lists 103 in each arm. The registry does not explain this difference in analysis denominators or specify the associated missing-data handling. No assumptions should be made about the reason for the smaller secondary denominators.

Multiplicity is relevant because the record lists five outcome measures and five analyses, including the primary endpoint and secondary outcomes at different times or addressing different questions. The registry reports p-values for the primary and posted secondary comparisons, but a family-wise or other multiplicity adjustment is not reported in the registry record. Without the analysis plan, it is not possible to determine which tests were designated confirmatory, whether a testing hierarchy was planned, or how the sponsor intended to interpret the collection of results.

Interim analyses, stopping rules, the trial’s originally planned significance threshold, and a complete statistical analysis plan are not reported in the registry record. These omissions do not invalidate the posted numbers, but they limit assessment of whether the analyses followed a prespecified strategy and how much emphasis should be placed on individual p-values. In particular, secondary results should be treated as supportive descriptions unless their status and multiplicity handling are established.

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: hidradenitis (1.9%), cardiovascular disorder (1.0%), cholelithiasis (1.0%), blastocystis infection (1.0%), postoperative wound infection (1.0%).

The safety summaries list serious adverse events among 3 participants in the placebo group and 7 in the adalimumab group; 103 participants were at risk in each arm. Other adverse events are listed for 43 participants in the placebo group and 48 in the adalimumab group. The registry also records 0 deaths in the placebo arm and 2 in the adalimumab arm. These are counts in the registry’s safety fields, not evidence by themselves that an event was caused by assigned treatment.

The record lists serious-event terms including HIDRADENITIS at 1.9%, and CARDIOVASCULAR DISORDER, CHOLELITHIASIS, BLASTOCYSTIS INFECTION, POSTOPERATIVE WOUND INFECTION, and RESPIRATORY TRACT INFECTION at 1.0% each. The time window for the safety summaries and the method used to determine whether events were treatment-related are not reported in the registry record. The listed terms should not be interpreted as a complete account of event severity, duration, or attribution.

Safety comparisons require context about exposure time, event definitions, follow-up, and clinical review. Those details are not reported in the registry record. The counts describe the posted safety information; they do not, on their own, establish a causal difference between groups or provide a complete assessment of safety.

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

The primary result describes a difference in the proportion meeting a particular response definition at Week 12 in a randomized comparison of adalimumab and placebo among surgical candidates with moderate to severe HS. The observed response proportion was higher in the adalimumab arm, and the unadjusted risk-difference interval is above zero but has a lower endpoint close to zero. The sponsor’s reported analysis gives a p-value close to the recalculated one. Together, these statistics describe the posted data and the uncertainty in the estimated comparison.

They do not establish how much an individual participant’s condition changed, because the endpoint reduces lesion-count information to whether a threshold was met. They do not show the full distribution of responses, nor do they establish that every participant experienced the same result. The endpoint also does not itself measure surgical-site area or whether surgery was reduced or avoided; those are separate outcomes.

The result should be interpreted as applying to the trial’s specified population, treatment context, assessment time, and NRI rule. The registry record describes participants as surgical candidates and the study objective as evaluating adalimumab prior to surgery. It does not report sufficient details about surgery timing and procedures to generalize the result to every peri-surgical setting.

A p-value is not a measure of clinical importance, and a confidence interval does not remove uncertainty about bias, missingness, or design implementation. The original statistical plan, multiplicity handling, and detailed missing-data information are not reported in the registry record. The secondary outcomes offer additional context but do not all address the same question, and the surface-area result is not reported.

Accordingly, the registry supports a careful description of a higher observed Week 12 response proportion in the adalimumab group, alongside uncertainty about the size and broader interpretation of the difference. It does not justify conclusions beyond the recorded outcomes and analyses, nor an individual treatment recommendation.

18. Why This Trial Matters Statistically

This trial is statistically informative because it puts a clearly defined response outcome into a randomized, placebo-controlled peri-surgical comparison. Random allocation is intended to make groups comparable on average, which supports a treatment-group comparison more directly than an observational contrast. The primary endpoint also states a concrete response rule, making its meaning more specific than a general claim of improvement.

The comparison illustrates why arm percentages, a between-group estimate, a confidence interval, and a p-value answer related but different questions. The arm percentages describe response in each group; the risk difference summarizes the contrast; the interval conveys uncertainty about its magnitude; and the p-value summarizes compatibility with a null model under a chosen test. The registry’s sponsor analysis and unadjusted recalculation are close, while still being methodologically distinct.

The record also illustrates the importance of analysis populations and missing-data rules. The primary outcome uses an intent-to-treat population with NRI, while the secondary surgery outcome has smaller arm denominators and no explanation of that difference. Interpretation therefore depends not only on the observed percentages but also on knowing who contributed to each analysis and how missing assessments were handled.

Finally, a trial with several outcomes raises questions about multiplicity and prespecification. The registry identifies primary and secondary outcomes, but does not report the full testing plan or multiplicity adjustment. That distinction matters when assessing the strength of the overall evidence: a primary result and a set of secondary comparisons do not necessarily carry the same inferential status. The record is useful for learning how to keep effect size, precision, analysis method, and reporting completeness in view at the same time.

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.

Several trial-specific limitations follow from gaps in the registry record. The original sample-size justification and planned effect size are not reported, so the enrollment of 206 cannot be judged against the trial’s intended power target. The planning illustrations based on the observed effect are not a substitute for the original design assumptions.

The primary result uses NRI for missing data, but the record does not report how many Week 12 assessments were missing or why. This prevents assessment of how sensitive the primary estimate might be to the imputation rule. For the surgery-related secondary endpoint, the arm denominators are 87 and 82, rather than the 103 participants listed in each primary arm. The reason for this difference and the analysis population definition are not reported in the registry record.

The record identifies the sponsor method as Cochran-Mantel-Haenszel but does not report its strata or a comparative estimate and confidence interval from that analysis. It also does not report the complete statistical analysis plan, multiplicity adjustment, interim analyses, or stopping rules. These omissions restrict evaluation of prespecification and the interpretation of several p-values together.

HiSCR-es is listed as a secondary outcome, but its definition is not reported in the registry record. The numerical result for change in HS surgical-site surface area is also not reported. Safety reporting lacks a stated timeframe and does not provide event attribution details in the posted fields. These are reporting limitations rather than proof that the underlying trial did not collect such information.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety and Efficacy of Adalimumab (Humira) for Hidradenitis Suppurativa (HS) Peri-Surgically — NCT02808975.
• Registry record last updated 2020-05-14; status last verified 2020-05.
• Results first posted 2020-05-14.
• 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

The registry describes a completed phase 4, randomized, parallel, placebo-controlled, multicenter study of adalimumab used in conjunction with surgery for moderate to severe hidradenitis suppurativa. Enrollment was 206, with 103 participants listed in each primary arm. The primary endpoint was HiSCR at Week 12 in the intent-to-treat population, using non-responder imputation for missing data.

The posted primary response proportions were 34.0% for placebo and 47.6% for adalimumab. The unadjusted recalculated risk difference was 0.136, with a 95% confidence interval from 0.003 to 0.269 and p = 0.047. The registry-reported Cochran-Mantel-Haenszel analysis gives p = 0.049. Secondary outcomes show a mixed level of precision, and numerical results for surgical-site surface-area change are not reported in the registry record.

The registry does not report the original sample-size justification, full analysis plan, multiplicity handling, or detailed missing-data information. These gaps limit interpretation of the broader analysis strategy and the secondary results.