Observe the Frequency of Extra-Axial Symptoms in Korean Ankylosing Spondylitis (AS) Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Observe the Frequency of Extra-Axial Symptoms in Korean Ankylosing Spondylitis (AS) Patients (NCT02333383), a registered phase not stated study. The primary outcome is Frequency of Extra-Axial Manifestations (EAMs) of Interest.

2. Clinical Question

The endpoint focuses on the frequency of manifestations outside the axial features of ankylosing spondylitis. Peripheral arthritis was identified by at least one swollen joint on the specified joint-count scale. Enthesitis was identified by an inflamed enthesis on the specified assessment or by plantar fascia involvement. Dactylitis was assessed by counting affected digits. These definitions set out what qualified as a manifestation for the baseline assessment; they do not, by themselves, give the number or percentage of participants who met each definition.

The study also listed secondary outcomes relating to disease activity and musculoskeletal manifestations. The registry record describes treatment and follow-up in routine clinical practice, not a comparison of adalimumab with another treatment or with no treatment. The numerical primary result and numerical secondary results are not reported in the registry record. Consequently, the clinical question can be described from the endpoint definition, but its observed answer cannot be read from the posted results.

3. Trial Design

This was a prospective, mono-country, multicenter observational study of extra-axial manifestations in participants with ankylosing spondylitis receiving adalimumab in routine clinical practice. The registry lists enrollment of 201 participants and an overall status of completed. The recorded study start was 2014-12-31, and the recorded primary completion date was 2017-08-08.

The treatment description specifies adalimumab 40 mg by subcutaneous injection every other week for 52 weeks. The primary endpoint, however, concerns the baseline assessment performed before the first dose. The record defines the primary population as participants who received at least one dose and had extra-axial manifestations assessed at baseline. This distinction matters: the primary endpoint is a description of manifestations at the start of treatment, not a measure of change over the treatment period.

No comparator arm is described, and the record does not state an allocation method. It therefore does not support a like-for-like treatment comparison. The study description emphasizes observation in routine clinical practice, rather than assignment to competing interventions. The registry record does not report additional details about how clinical sites selected participants, how treatment decisions were made, or whether treatment use differed among participants.

The outcomes listed beyond the primary endpoint include measures of disease activity, enthesitis, plantar fascia involvement, dactylitis, and joint counts. Their presence in the registry identifies planned or recorded outcome topics, but does not establish that numerical results for each are available. The record lists seven outcome measures and zero analyses. More detail on analysis procedures, including any prespecified statistical plan, is not reported in the registry record. The study design supports describing the setting and endpoint definitions, but the absent numerical endpoint results limit interpretation of the observed frequency.

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: Intention-to-Treat (ITT) population: Participants who received at least one dose of adalimumab and had extra-axial manifestations (EAMs) assessed at baseline

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention-to-Treat (ITT) population: Participants who received at least one dose of adalimumab and had extra-axial manifestations (EAMs) assessed at baseline

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: Intention-to-Treat (ITT) population: Participants who received at least one dose of adalimumab and had extra-axial manifestations (EAM) assessed at baseline

6. Primary Endpoint

The registry lists the primary outcome as Frequency of Extra-Axial Manifestations (EAMs) of Interest, measured over Baseline.

The primary endpoint is the frequency of extra-axial manifestations of interest at baseline, expressed as a percentage of participants. The assessment took place before the first adalimumab dose. It considered peripheral arthritis, enthesitis, and dactylitis, using definitions based on joint swelling, enthesis inflammation, and dactylitic digits, respectively.

A percentage is used to describe how common a defined feature is within the assessed population. For a clinical registry question about frequency, this scale is readily interpretable as a proportion of participants meeting the endpoint definition. The endpoint definition is important because frequency estimates depend on what counts as a case. Here, the record specifies the relevant joint-count and enthesitis criteria, including plantar fascia involvement, as well as the digit-count approach to dactylitis.

The registry identifies a 95% confidence interval as the dispersion measure. In general, a confidence interval conveys the statistical uncertainty around an estimate; it does not remove uncertainty arising from participant selection, measurement, or the clinical setting. The endpoint’s numerical percentage and confidence interval are not reported in the registry record, so neither its estimated frequency nor its precision can be described from the posted results.

Because the assessment occurred before treatment began, the endpoint is descriptive of baseline status. It is not an estimate of treatment response, a change from baseline, or a comparative treatment effect. The registry’s secondary outcomes include measures of change or response, but those are separate questions and their numerical results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint describe?

In general, a percentage endpoint expresses the share of an assessed population that meets a specified definition. Its interpretation depends on both the case definition and the denominator. In this study, the endpoint concerns the percentage of participants with extra-axial manifestations at baseline. The record defines the manifestations and identifies the primary population, but does not report the numerical percentage or the count assessed for the endpoint. The enrollment figure alone cannot establish the endpoint denominator, because the primary population definition also requires receipt of at least one dose and baseline assessment.

What does the confidence interval add?

In general, a confidence interval describes statistical uncertainty around an estimate under a specified method and its assumptions. It is not a range containing every participant’s outcome, and it does not account automatically for all possible sources of bias. The registry lists a 95% confidence interval for the primary percentage. The interval’s endpoints are not reported in the registry record, so its width and the precision of the estimate cannot be assessed.

Why do endpoint definitions matter?

Definitions determine which observations count toward an endpoint. Peripheral arthritis was defined by at least one swollen joint on the Swollen Joint Count scale, which ranges from 0 to 44 and excludes hip joints. Enthesitis was defined as at least one inflamed enthesis on the Maastricht Ankylosing Spondylitis Enthesitis Score, which ranges from 0 to 13, or involvement of the plantar fascia of the foot. Dactylitis was measured by a simple count of affected digits. The record notes that higher Maastricht score values represent more severe disease. These definitions make the target measurement more specific, but they do not reveal how many participants met any criterion.

Why is baseline timing important?

The primary assessment was performed before the first adalimumab dose. It therefore describes baseline status rather than change after treatment. The secondary outcomes include response and change measures, which address different statistical questions. A baseline frequency cannot by itself establish a treatment effect, because it does not compare outcomes under alternative treatment conditions or quantify change over time.

What can be inferred from the design?

The study is described as prospective, mono-country, multicenter, and conducted in routine clinical practice. The record specifies a treatment regimen of adalimumab 40 mg every other week by subcutaneous injection for 52 weeks. It does not describe a comparator group or state an allocation method. As a result, there is no randomized treatment contrast described in the record. General causal interpretation requires more than observing participants who receive a treatment; the design and analysis must support separating treatment effects from other explanations. The information does not provide such a comparison.

How should planning calculations be understood?

General sample-size calculations are conditional planning exercises. The record’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect stated as a fraction of the observed effect. Those assumptions describe an illustrative calculation, not the study’s own design. The study is described without a comparator arm, and the registry record does not report a sample-size justification or establish that the planning assumptions governed enrollment. Planning estimates are not observed power and do not determine whether the study produced an informative result. Numerical planning estimates are not reported in the registry record.

For a two-arm planning calculation in general, equal allocation means the hypothetical participants are split evenly across the assumed arms. A normal approximation is a mathematical method used to estimate a sampling distribution under its assumptions. These conventions can make a planning exercise tractable, but their use does not demonstrate that a corresponding two-arm trial occurred. Nor does a significance-level assumption indicate that a statistical test was performed for the baseline frequency endpoint.

What role can over-dispersion play?

In general, over-dispersion occurs when outcome variability exceeds what a chosen statistical model assumes. It can make standard errors too small if the model fails to allow for the extra variability, leading to confidence intervals that appear more precise than warranted. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report a model for the primary endpoint or an assessment of over-dispersion. Therefore, it is not possible to say whether this issue was assessed or affected the reported analysis.

Are there recalculated estimates?

No recalculated primary estimate is available from the registry information. A recalculation would require the relevant numerical summary statistics, and the primary percentage and its interval are not reported in the registry record. There is also no reported sponsor estimate to compare with an unadjusted recalculation. The posted results therefore support describing the endpoint and its stated precision measure, but not reconstructing an estimate or evaluating a discrepancy.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, including the primary frequency endpoint and secondary measures of disease activity and extra-axial manifestations. When multiple outcomes are examined, multiplicity can arise because repeated statistical tests increase the chance of at least one apparently notable result by chance. In general, a statistical plan may address this through a hierarchy of outcomes, an adjustment procedure, or a clearly descriptive interpretation. A multiplicity strategy is not reported in the registry record.

The record lists zero analyses. This describes the registry’s analysis reporting; it does not establish whether analyses were conducted outside the registry or whether the outcome measures were prespecified in a separate document. Any statistical analysis plan, interim analysis procedure, or adjustment method is not reported in the registry record. No p-values or numerical outcome estimates are reported for assessing how the listed outcomes were analyzed.

The primary population is defined as participants who received at least one dose of adalimumab and had extra-axial manifestations assessed at baseline. This is the population specified for the primary endpoint. The number included in that endpoint analysis is not reported in the registry record. The enrollment figure should not be assumed to equal the analyzed population, because the endpoint definition includes additional eligibility conditions.

Missing-data procedures, reasons for missing assessments, and any imputation method are not reported in the registry record. Without those details, readers cannot determine how incomplete assessments were handled or whether missingness could affect the estimated frequency. The record also does not describe analysis populations for the secondary outcomes. These omissions limit assessment of reproducibility and of how closely the analysis population may correspond to the enrolled population.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: toxic skin eruption (0.5%), cellulitis (0.5%), pneumonia (0.5%), fibromyalgia (0.5%), diarrhoea (0.5%).

The registry reports serious adverse event figures for the group titled Participants with Ankylosing Spondylitis: 8 affected among 201 at risk. It reports other adverse event figures of 18 affected among 201 at risk, and deaths of 0. These are separate registry categories. The record does not provide enough detail to infer overlap between categories or to treat the counts as counts of distinct events.

The listed serious event terms are toxic skin eruption, cellulitis, pneumonia, fibromyalgia, diarrhoea, and pancreatitis, each reported as 0.5%. These entries describe terms and percentages in the registry record; they do not establish that treatment caused the events. The record does not provide a comparison group or a causal analysis for these safety figures.

For general interpretation, safety counts depend on the population monitored, observation period, event definitions, and reporting procedures. The registry record does not state the timeframe attached to these figures or provide further detail on event ascertainment. The counts should therefore be read as reported safety observations, not as comparative risks or evidence that an event was caused or not caused by adalimumab. No rate or comparison is calculated.

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

The record establishes that a prospective, multicenter study was conducted to observe extra-axial manifestations in participants with ankylosing spondylitis receiving adalimumab in routine clinical practice. It specifies the baseline endpoint, the definitions used for peripheral arthritis, enthesitis, and dactylitis, and the intended treatment regimen. This information explains the clinical question and how its principal measure was defined.

The central numerical result needed to answer that question—the baseline percentage of participants with the manifestations of interest—is not reported in the registry record. Its 95% confidence interval is also not reported. Therefore, the posted results do not show the estimated frequency or how precise that estimate was. The study’s enrollment figure does not fill this gap, because the primary endpoint population requires a baseline assessment and receipt of at least one dose.

The record does not describe a comparator group or state an allocation method. Accordingly, it does not support a randomized comparison of adalimumab with another treatment or with no treatment. The primary assessment took place before the first dose, so it is a baseline description rather than a measure of treatment response. The regimen’s stated duration does not change the timing or interpretation of that primary endpoint.

The adverse event counts and listed event terms provide safety information as recorded, but they do not establish causation. Without a comparison group and further details about observation and ascertainment, they should not be interpreted as comparative treatment risks. The listed secondary outcome topics likewise do not establish clinical changes or responses, because their numerical results are not reported in the registry record.

In general, registry records are most informative when endpoint definitions, analysis populations, numerical estimates, uncertainty measures, and missing-data procedures are all available. Several of those elements are not reported for this study. The record can therefore support a description of study design and measurement, but not a numerical conclusion about the primary frequency, a treatment effect, or the precision of the observed result.

13. Why This Trial Matters Statistically

This study illustrates why a clearly defined clinical endpoint is only one part of a statistical result. The registry describes what counted as peripheral arthritis, enthesitis, or dactylitis and states that the primary outcome was a baseline percentage. Those details make the intended measurement understandable. Yet without the numerical estimate and its confidence interval, the frequency itself and its precision remain unknown from the registry record.

The distinction between enrollment and analysis population is also important. Enrollment is recorded as 201, while the primary population is restricted to participants who received at least one dose and had the baseline manifestations assessment. The record does not report how many participants met that endpoint-population definition. In general, analysis denominators should be interpreted from the population definition and analysis reporting, rather than assumed from enrollment.

The study also demonstrates the difference between describing a treated cohort and estimating a comparative treatment effect. The record describes adalimumab use in routine clinical practice but does not describe a comparator or allocation method. A baseline frequency is a descriptive quantity, and it is not evidence of change attributable to treatment. This distinction is central when interpreting observational clinical research.

Finally, the registry lists several outcome measures but reports zero analyses. This makes the availability of outcome results and analysis methods especially important to distinguish from the existence of outcome definitions. The record’s specified planning assumptions are not the same as the study design, and planning calculations do not represent observed power. Together, these points show why interpretation depends on transparent reporting of estimates, uncertainty, populations, and methods—not only on the clinical question or treatment description.

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 main limitation for statistical interpretation is that the numerical primary outcome is not reported in the registry record. The percentage and 95% confidence interval are unavailable, so the observed baseline frequency and its precision cannot be assessed. The record also does not report the number of participants included in the primary endpoint analysis. Although enrollment is listed as 201, the primary population definition requires receipt of at least one dose and a baseline assessment, and the analyzed denominator is not stated.

The study has no comparator group described in the registry record, and allocation is not stated. The design therefore does not provide a like-for-like control comparison. The primary outcome was assessed before treatment, which further limits interpretation to baseline status rather than treatment response. The treatment regimen is reported, but that alone does not establish a treatment effect.

Additional limitations include the absence of reported numerical results for the listed secondary outcomes and the registry’s listing of zero analyses. The statistical analysis plan, multiplicity approach, missing-data procedures, and interim-analysis details are not reported in the registry record. The record also does not provide further information about participant selection, site-level enrollment, or the timeframe associated with adverse event counts. These gaps limit assessment of reproducibility, selection, and the interpretation of incomplete data.

The study is described as mono-country and multicenter, with participants receiving treatment in routine clinical practice. That setting is relevant context, but the record does not establish how broadly the findings would apply beyond the studied participants and setting. Because the primary numerical result is absent, no estimate of the magnitude of the baseline frequency can be discussed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Observe the Frequency of Extra-Axial Symptoms in Korean Ankylosing Spondylitis (AS) Patients — NCT02333383.
• Registry record last updated 2019-01-15; status last verified 2018-07.
• Results first posted 2019-01-15.
• 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, prospective, mono-country, multicenter study of extra-axial manifestations in participants with ankylosing spondylitis receiving adalimumab in routine clinical practice. Enrollment is recorded as 201. The treatment regimen was adalimumab 40 mg by subcutaneous injection every other week for 52 weeks.

The primary endpoint was the baseline percentage of participants with manifestations of interest, assessed before the first dose. The endpoint covered peripheral arthritis, enthesitis, and dactylitis, with definitions specified in the registry. The record lists a 95% confidence interval as the dispersion measure and defines the primary population as participants who received at least one dose and had baseline assessment.

The numerical primary result and its confidence interval are not reported in the registry record. Secondary outcome topics are listed, but their numerical results and analysis details are not reported. The safety record lists 8 serious adverse events, 18 other adverse events, and 0 deaths among 201 at risk, along with serious event terms reported at 0.5% each. These safety observations do not establish causation or a comparative risk.