Human Anti-tumor Necrosis Factor (TNF) Monoclonal Antibody Adalimumab in Subjects With Active Ankylosing Spondylitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Human Anti-tumor Necrosis Factor (TNF) Monoclonal Antibody Adalimumab in Subjects With Active Ankylosing Spondylitis (NCT00085644), a randomized phase 3 study. The primary outcome is Number of Responders With a Reduction of Signs and Symptoms of Ankylosing Spondylitis (AS) as Measured With ASAS International Working Group Response Criteria (ASAS 20)..

2. Clinical Question

The trial’s objective was to evaluate safety and efficacy in people with active ankylosing spondylitis and the stated treatment history. The principal statistical question is therefore about the comparative frequency of a defined response at the stated assessment time, not simply whether an individual participant’s symptoms changed. A randomized comparison can address a treatment contrast when group-level results and the analysis details are available. Those primary results are not reported in the registry record.

3. Trial Design

This was a Phase 3, randomized, double-masked, parallel-group study. Its official title describes it as a multicenter study. The registry lists an enrollment of 315 and identifies adalimumab and placebo as the interventions. It does not provide the number assigned to each group, the number analyzed for the primary endpoint, or a fuller account of participant flow.

The registry lists the study as completed. The start is recorded as 2004-01 and primary completion as 2004-12. Abbott is identified as the sponsor. These record details describe the trial’s status and administration; they do not establish how the study was conducted in every operational respect. For example, the registry record does not report the randomization method, concealment procedure, or the procedures used to maintain masking.

The primary endpoint was the number of participants meeting ASAS 20 criteria at Week 12. The listed secondary outcomes include ASAS 20, ASAS 50, and ASAS 70 responses and changes in patient’s global assessment, BASFI, and total back pain. Several of those outcomes are described through Week 260 of adalimumab exposure. These long-term outcome descriptions concern adalimumab exposure and should not be mistaken for a continued placebo-controlled comparison; the registry record does not establish the design or analysis details for each later assessment.

The record lists 37 outcome measures and 2 analyses, but does not identify a complete statistical analysis plan or explain how all outcomes were analyzed. It also does not report group-specific baseline summaries, endpoint denominators, or a primary treatment-effect estimate. Without those details, the design can be characterized from the registry, but the precision and interpretation of the primary comparison cannot be assessed.

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: Subjects were randomized 2:1 to receive either 40 mg adalimumab subcutaneous (sc) every other week (eow) or matched placebo for the 24-week double-blind placebo-controlled period of the study. After 12 weeks, subjects without a reduction of signs and symptoms in ankylosing spondylitis (ASAS 20) were considered for open-label adalimumab treatment.

Double-Blind Period

Reasons for not completing this period:

Open-Label Period

Reasons for not completing this period:

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 Responders With a Reduction of Signs and Symptoms of Ankylosing Spondylitis (AS) as Measured With ASAS International Working Group Response Criteria (ASAS 20)., measured over Week 12.

The primary endpoint counts participants who met ASAS 20 response criteria at Week 12. A responder needed an improvement of >=20% and an absolute improvement of >=10 units from baseline in at least 3 of 4 domains: patient’s global assessment of disease activity, total back pain, BASFI, and inflammation. The definition also required no deterioration in the potential remaining domain, defined as worsening of >=20% and a net worsening of >=10 units.

The registry describes the scales used for these domains, including visual analog scales for global assessment, back pain, BASFI, and inflammation. It emphasizes that the criteria are applied to each scale rather than to an overall global scale. Thus, ASAS 20 is a composite response classification built from changes across multiple domains, rather than a single measurement or an average change across all domains.

General statistical context: a prespecified response threshold can make a result easier to interpret as the proportion meeting a defined standard, while compressing the amount of information in continuous scale changes. Participants just on either side of a threshold may have similar measured changes but receive different classifications. The registry record does not report the number meeting the endpoint in either group, so the observed response proportions and their uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: the interpretation of a clinical-trial result begins with the estimand—the treatment effect the analysis is intended to describe—and the endpoint used to measure it. The registry identifies ASAS 20 response at Week 12 as the primary endpoint. It defines a responder using improvements across specified disease-assessment domains, together with a restriction on worsening in the remaining domain. The record does not report a formal estimand, such as whether the intended effect concerns assignment to treatment regardless of later treatment changes or exposure while taking assigned treatment.

What does a randomized comparison contribute?

In general, random allocation is used to make treatment groups comparable on average at the start of a trial, including with respect to factors that may not have been measured. A between-group comparison can then estimate the effect associated with assignment, subject to the trial’s conduct, follow-up, and analysis. Randomization does not guarantee that every group characteristic is identical, and it does not replace reporting group sizes, outcomes, and analytic choices. The registry record labels this trial randomized but does not report the allocation sequence, allocation concealment, or group-specific primary endpoint results.

Double masking is intended to reduce the influence of knowledge of treatment assignment on care, participant reporting, or outcome assessment. Its practical contribution depends on how masking was implemented and whether it remained intact. Those operational details are not reported in the registry record. The parallel-group label indicates that the record classifies the study as comparing groups in parallel; further details of the treatment schedule and follow-up are not reported.

How should a response endpoint be understood?

ASAS 20 converts changes in several scales into a responder classification. The definition requires improvement of >=20% and >=10 units in at least 3 of 4 domains, with no qualifying deterioration in the remaining domain. This rule combines relative and absolute change criteria. General statistical context: using both types of threshold can avoid defining response solely by a proportional change or solely by an absolute scale shift. However, classifying participants as responders or nonresponders loses some detail about the size and pattern of changes within each domain.

The endpoint is a count of participants in response categories, not a mean change on a continuous scale. To compare groups, analysts would ordinarily use the response counts and denominators for each group, then report a treatment contrast with an uncertainty measure. The exact contrast and statistical method depend on the analysis plan. Neither the counts nor the method for the primary comparison is reported in the registry record, so no specific effect measure or test can be attributed to the trial from these registry entries.

What does precision mean?

General statistical context: a confidence interval represents uncertainty around an estimated effect under the assumptions of its method. It is not a guarantee that the true effect lies within the interval, nor does it describe the probability that a particular treatment effect is true. A confidence interval is most useful when read with the estimate, endpoint definition, analysis population, and missing-data approach. The primary endpoint estimate and interval are not reported in the registry record.

A p-value, if reported, would describe how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of the test. It is not a measure of effect size, clinical relevance, or the probability that the null hypothesis is true. The registry entries do not include a primary endpoint p-value, test specification, or a complete statistical analysis plan. Therefore, no trial-specific p-value interpretation can be made.

What do the planning assumptions describe?

The registry entries describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustration is described as targeting a stated fraction of the observed effect. These are planning assumptions, not a report of the trial’s original design justification. The registry record does not report the original sample-size justification or the calculated planning values in the registry record.

General statistical context: a planning illustration asks what sample size might be needed under chosen assumptions about the effect, significance level, allocation, and statistical method. It is conditional on those assumptions and does not describe what the trial actually observed. It should not be confused with observed power, which is not a substitute for reporting an effect estimate and its uncertainty. No sample-size values can be interpreted from the registry entries.

Why can dispersion matter?

General statistical context: for count outcomes, the variability of counts can exceed what a simple model assumes. This is called over-dispersion. If it is present and ignored, standard errors and confidence intervals may be too small, making an analysis appear more precise than it is. The primary endpoint is described as a count of responders and nonresponders, but the registry record does not report a model, dispersion estimate, or a count-model analysis. No claim about over-dispersion in this trial is warranted.

The registry lists 37 outcome measures and 2 analyses. Those listings do not reveal which outcomes were included in each analysis, which models were used, whether estimates were adjusted, or how uncertainty was calculated. The analysis methods for the primary endpoint are not reported in the registry record. Accordingly, the statistical concepts above explain how such results are generally read; they do not describe an undocumented method used in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint, multiple secondary outcomes, 37 outcome measures, and 2 analyses. The record does not report how the primary and secondary analyses were organized, whether any outcomes were designated for confirmatory testing, or how the possibility of multiple statistical comparisons was addressed. A multiplicity adjustment or testing hierarchy is not reported in the registry record.

General statistical context: when many outcomes or repeated comparisons are examined, the chance of at least one apparently unusual result can increase if each is interpreted without regard to the others. Prespecified testing strategies can help define which findings are confirmatory and how they should be interpreted. Without the analysis plan and outcome-level results, it is not possible to assess whether or how multiplicity influenced the reported analyses.

The registry record also does not report the number of participants with missing Week 12 assessments, the reasons for missingness, or how missing primary endpoint data were handled. It does not describe imputation, sensitivity analyses, or assumptions about participants with unavailable outcomes. These omissions matter because the treatment comparison can depend on how missing outcomes are treated, particularly when the endpoint is classified as responder or nonresponder.

Analysis populations are also not described in the registry entries. The record does not state whether the primary analysis included all randomized participants, participants who received treatment, or another defined group. It does not report how protocol deviations, treatment discontinuation, or changes in treatment were handled for the primary endpoint. These details are not reported in the registry record and should not be inferred from the randomized design label.

11. 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: chest pain (1.6%), myocardial infarction (1.3%), ankylosing spondylitis (1.3%), atrial fibrillation (1.0%), coronary artery disease (1.0%).

The registry lists an Any Adalimumab group with 311 participants at risk for the serious adverse event summary and 96 affected. For the other adverse event summary, it lists 311 at risk and 279 affected. These are registry counts, not recalculated rates. The record does not provide a corresponding placebo-group summary in the registry record, so these figures do not form a randomized comparison between adalimumab and placebo.

The record also lists the most frequent serious adverse event terms with percentages: Chest pain, 1.6%; Myocardial infarction, 1.3%; Ankylosing spondylitis, 1.3%; Atrial fibrillation, 1.0%; Coronary artery disease, 1.0%; and Cellullitis, 1.0%. These are presented as event terms and percentages; the associated event counts are not reported in the registry entries.

General statistical context: adverse-event summaries depend on how events are defined, collected, coded, and attributed, as well as the period during which participants were observed. A count of affected participants does not communicate event duration, severity beyond the category shown, recurrence, or comparative risk on its own. The registry entries do not provide the observation time, detailed event definitions, or a placebo comparison for these summaries. The figures should therefore be read as descriptive safety information for the stated group, not as proof of a causal difference or a complete account of safety.

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

The registry record establishes that a randomized, double-masked, parallel-group Phase 3 study evaluated adalimumab and placebo in people with active ankylosing spondylitis. It specifies the primary endpoint as the number of ASAS 20 responders at Week 12 and gives the response definition. These details explain what the trial set out to compare, but the primary response counts and treatment-effect estimate are not reported in the registry record.

As a result, the record does not support a conclusion about whether the groups differed on the primary endpoint, how large any difference was, or how precisely it was estimated. It also does not support a statement about statistical significance. The absence of primary results in the registry record should not be interpreted as evidence of no effect or as evidence of an effect.

The listed secondary outcomes provide context about the types of measures tracked, including response thresholds and changes in disease assessments. Their descriptions alone do not establish their observed results. Outcomes described through Week 260 of adalimumab exposure do not, without further design and analysis information, establish a long-term placebo-controlled comparison.

The safety summaries report affected participants in an Any Adalimumab group and list serious event terms with percentages. They do not provide a placebo-group contrast in the registry record. The counts therefore should not be treated as comparative risks, and the listed event percentages should not be used to infer causation or an individual participant’s likelihood of an event.

General statistical context: treatment effects are best interpreted using the endpoint definition, group-specific data, an effect estimate, uncertainty, analysis population, and handling of missing outcomes. Several of these elements are not reported in the registry record. The trial design is relevant to how a reported result might be interpreted, but design labels cannot replace the results and analysis details needed to assess the comparison.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a randomized comparison built around a multidomain response endpoint. ASAS 20 uses thresholds across patient’s global assessment, back pain, physical function, and inflammation, and also considers worsening in the remaining domain. Understanding that definition is necessary before interpreting any responder count: it shows that response is a rule-based classification rather than a single-scale change.

The study record also illustrates why design information and outcome information answer different questions. Randomization, masking, and a parallel-group structure describe the intended framework for comparing treatments. They do not indicate what the comparison found. In this record, the primary outcome counts and treatment-effect estimate are not reported, leaving the primary statistical question unresolved by the registry entries.

The listed longer-term outcomes highlight another interpretive issue. An outcome measured during adalimumab exposure is not automatically equivalent to a continuing randomized comparison against placebo. The analysis population, treatment changes, follow-up, and comparator status matter for interpreting later observations, and those details are not reported in the registry record.

Finally, the safety summaries show the importance of distinguishing descriptive counts from comparative evidence. An affected-participant count in an Any Adalimumab group cannot establish a difference from placebo when the corresponding comparator summary is unavailable. General statistical context: treatment comparisons require clearly defined denominators and comparable observation periods, alongside uncertainty estimates. The record’s limited reporting makes those distinctions especially relevant when reading the available safety information.

14. 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 central limitation for statistical interpretation is that the registry entries do not report primary endpoint responder counts by randomized group, a treatment-effect estimate, a confidence interval, or a p-value. The number enrolled does not resolve this gap because group-specific allocation and endpoint denominators are not reported. The primary comparison therefore cannot be quantified from the registry record.

The record does not report the statistical analysis plan, the primary analysis population, the method used for the endpoint comparison, or adjustment choices. It also does not report missing Week 12 data, reasons for missingness, or methods for addressing missing outcomes. These omissions limit assessment of the analysis and its sensitivity to analytic assumptions.

Although multiple secondary outcomes are listed, their results and the approach to multiplicity are not reported in the registry record. The record lists outcomes through Week 260 of adalimumab exposure, but does not provide sufficient details to characterize the later follow-up or interpret it as a randomized comparison with placebo. No conclusion about long-term comparative effects can be drawn from outcome labels alone.

Safety information is also incomplete for comparative interpretation. The Any Adalimumab group has serious and other affected-participant summaries, but a placebo-group summary and relevant observation-time details are not reported in the registry entries. The listed serious event percentages do not include event counts.

Finally, the registry record gives limited detail about eligibility beyond the study description, baseline characteristics, treatment adherence, allocation procedures, and maintenance of masking. These limitations do not negate the design features that are reported, but they constrain evaluation of trial conduct, generalizability, and the statistical evidence available from this record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Human Anti-tumor Necrosis Factor (TNF) Monoclonal Antibody Adalimumab in Subjects With Active Ankylosing Spondylitis — NCT00085644.
• Registry record last updated 2011-04-21; status last verified 2011-04.
• Results first posted 2010-03-11.
• 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.

18. Record Summary

The registry describes a completed, randomized, double-masked, parallel-group Phase 3 multicenter study sponsored by Abbott. It lists enrollment of 315 and compares adalimumab 40 mg every other week with placebo in people with active ankylosing spondylitis and the stated prior treatment history.

The primary endpoint is the number of participants meeting ASAS 20 response criteria at Week 12. The registry entries describe the criteria but do not report the primary response counts by group or a treatment-effect estimate. The record lists secondary outcomes, including measures through Week 260 of adalimumab exposure, and provides descriptive safety summaries for an Any Adalimumab group. It does not provide the analysis details, missing-data handling, or comparative safety results needed for fuller statistical interpretation.