A Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis (NCT00667355), a na phase 3 study. The primary outcome is Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12.

2. Clinical Question

The clinical question is therefore about the observed response within a treated group, rather than a comparative treatment effect. ASAS 20 combines changes in patient global assessment, pain, function, and inflammation. Meeting the criterion requires improvement across multiple domains and no qualifying worsening in the remaining domain. This makes the endpoint more structured than a single symptom rating, while still expressing response as a threshold-based count.

The study also lists secondary outcomes involving higher ASAS response thresholds, BASDAI 50, and changes in disease activity, pain, function, and C-reactive protein. Their inclusion indicates a broader assessment of clinical and laboratory outcomes, but the registry record does not report their results. The available record therefore defines what the trial set out to assess more clearly than what it found.

3. Trial Design

This was a Phase 3, multicenter, open-label study of adalimumab in Japanese subjects with active ankylosing spondylitis. It is recorded as a single-group study, with no random allocation and no masking. The registry record identifies Abbott as the sponsor and reports that the study is completed. The listed study dates are 2008-02 for start and 2009-05 for primary completion.

The study enrollment is reported as 41. All subjects received adalimumab 40 mg subcutaneously at baseline. The arm description also refers to adalimumab 40 mg or 80 mg administered every other week, but its account of subsequent treatment is cut off. The full treatment sequence and the criteria governing any change in dose are not reported in the registry record.

Because there is a single treatment group, the design can describe outcomes among participants receiving the study treatment, but it does not provide a concurrent untreated or active-comparator group. Changes from baseline may be described, but without a randomized comparison they cannot by themselves separate treatment-associated change from other influences over time. Open-label conduct also means that treatment assignment was not masked.

The primary endpoint is the number of subjects achieving ASAS 20 at Week 12. The registry record lists 19 outcome measures and several secondary measures, but reports no analyses in the record. Protocol details such as the statistical analysis plan, sample-size justification, and any interim analyses 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: For all non-responder imputation (NRI) analyses, subjects with a missing value at a visit were imputed as a non-responder for that visit. Observed cases is based on a total of 40 subjects analyzed (vs. 41 subjects for the study and all other analysis sets) due to 1 subject who discontinued prior to Week 12.

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 Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12, measured over Week 12.

The primary endpoint is the number of subjects achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12. ASAS is a composite measure with four domains: patient global assessment of disease activity, pain, function, and inflammation. The criterion requires at least 20% improvement from baseline and an absolute improvement of at least 10 units on a 0 - 100 scale in at least three domains. The remaining domain must not show worsening meeting the specified threshold.

A multi-domain response is used to capture improvement across different aspects of ankylosing spondylitis rather than relying on a single symptom. The threshold also gives a defined rule for classifying each subject as a responder or non-responder. The primary measure is a count, so its interpretation depends on both the response rule and the population included in the analysis.

The registry record names the endpoint and its Week 12 timeframe but does not report the number of responders. It also does not report an uncertainty interval or a formal statistical comparison for this endpoint. As a result, the endpoint definition can be explained, but the magnitude and precision of the observed response cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how outcomes are summarized, how missing observations are handled, and how uncertainty is represented. For this study, the registry record identifies a binary primary outcome: each subject either meets the ASAS 20 response definition at Week 12 or does not. The primary measure is a count of responders. No primary result or statistical analysis is reported in the registry record, so the observed response and its uncertainty cannot be interpreted from the available record.

What does a responder count represent?

A responder count applies a prespecified or recorded threshold to each subject's measurements and counts those meeting the rule. ASAS 20 requires improvement in at least three of four domains, with a minimum relative and absolute change, while also requiring no qualifying worsening in the remaining domain. The count is therefore not a direct summary of the average change in any one domain. It classifies outcomes using the combined rule.

For a count to be interpretable, its analysis population and missing-data approach matter. A count alone does not specify whether all enrolled subjects were included, whether missing observations were excluded, or whether missing outcomes were assigned a response status. The registry record describes more than one analysis approach but does not provide the primary result itself.

What is non-responder imputation?

In the registry description, non-responder imputation treats a subject with a missing value at a visit as a non-responder at that visit. This is a conservative classification in the sense that missingness does not count as evidence of meeting the response threshold. It is still an assumption about the unobserved outcome, not a direct observation of the subject's status.

Non-responder imputation can make the outcome depend on both response and missingness. If missing observations occur, the count may reflect the imputation rule as well as observed responses. The record does not report how many values were missing at the primary visit, why they were missing, or the outcome under alternative missing-data assumptions. Those details are not reported in the registry record.

What is an observed-cases analysis?

An observed-cases analysis uses the outcomes available for assessment rather than assigning a response status to missing values under the non-responder rule. The registry record says that its observed-cases analysis was based on 40 subjects, while the study and other analysis sets involved 41. It attributes the difference to one subject who discontinued before a point in the sentence that is incomplete in the record. The precise timing or reason for that discontinuation is not reported in the registry record.

Observed-case and non-responder-imputation results answer somewhat different questions because they treat missing outcomes differently. Comparing them can be informative when both are reported, but the registry record does not report the relevant estimates. It is therefore not possible to judge whether the endpoint result is sensitive to the missing-data method.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the observed data under the statistical model and method used. For a responder count or proportion, it would help readers assess precision rather than relying only on a point estimate. The registry record does not report a confidence interval for the primary endpoint, and no interval can be inferred from the record without performing a new calculation.

In general, a p-value addresses how compatible observed data are with a specified null model; it does not measure the probability that a treatment works, nor does it describe the size of an effect. No primary p-value is reported in the registry record. The record also does not report the inferential model, hypothesis, or adjustment strategy for the primary analysis.

What can a single-group design estimate?

A single-group study can report outcomes observed among people receiving the study treatment. It does not, on its own, supply a concurrent estimate of outcomes under a different treatment. A change from baseline can reflect treatment and other influences, including the natural course of disease, measurement variation, and changes over time. This is a general limitation of uncontrolled before-and-after evidence, not a finding about the causes of any change in this study.

Random allocation in a comparative study can support a more direct comparison by balancing prognostic factors on average across groups. This study is recorded as single-group, with allocation listed as not applicable, and the record states that it is not a randomized comparison. No comparative treatment effect is available from this design.

What do the planning assumptions mean?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such calculations explore sample sizes for a hypothetical comparison under stated assumptions. They are not the study's observed power, do not represent the design of this single-group trial, and are not evidence of a treatment effect. The trial's own sample-size justification is not reported in the registry record.

Overall, the methods information defines some analysis populations and missing-data handling but leaves the main inferential details and outcome estimates unavailable. Without the primary result, uncertainty estimates, and a full statistical plan, statistical interpretation must remain descriptive and limited to the design and definitions recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 19 outcome measures, including the Week 12 ASAS 20 primary endpoint and secondary measures such as ASAS 50, ASAS 70, BASDAI 50, and changes in patient global assessment, back pain, function, and C-reactive protein. It reports zero analyses. No outcome estimates or inferential results are included, so the extent to which these measures were analyzed cannot be determined.

When multiple outcomes are tested, the chance of obtaining at least one apparently notable result can increase. Statistical methods can address multiplicity, for example by adjusting inference or by clearly distinguishing confirmatory from exploratory outcomes. This is a general statistical consideration. The registry record does not report a multiplicity strategy, a hierarchy among secondary endpoints, or which outcomes were formally tested.

For non-responder imputation analyses, the record states that a missing value at a visit was treated as a non-response for that visit. It also describes an observed-cases analysis based on 40 subjects, compared with 41 subjects in the study and other analysis sets, because one subject discontinued before an incomplete description point. The detailed reason and timing are not reported in the registry record.

The number and reasons for missing primary endpoint observations, and results under different missing-data assumptions, are not reported in the registry record. Without those details and the endpoint estimates, the impact of missingness or analysis-population choices cannot be assessed.

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: cataract (4.9%), thrombocytopenia (2.4%), intervertebral discitis (2.4%), osteomyelitis (2.4%), pneumonia (2.4%).

The registry record lists safety information for the adalimumab group, with 41 subjects at risk for serious adverse events and 6 affected. It also lists 41 subjects at risk for other adverse events and 41 affected. These are event categories reported in the record; they do not by themselves describe severity beyond the serious-versus-other classification or establish that treatment caused an event.

The listed serious adverse event terms include cataract at 4.9%, and thrombocytopenia, intervertebral discitis, osteomyelitis, pneumonia, and breast cancer at 2.4% each. These are registry-listed terms and percentages. They should be read as the record presents them, without inferring unreported details about timing, duration, outcome, or causal attribution.

Safety counts describe events observed in the study group, not comparative risks against a control group. Because this study has no concurrent comparator, the listed figures cannot show how event occurrence would differ under another treatment. The registry record does not report deaths in the listed group. Additional detail on event definitions, exposure duration, and individual event narratives is not reported in the registry record.

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

The registry record establishes that a Phase 3, open-label, single-group study evaluated adalimumab in Japanese subjects with active ankylosing spondylitis. It specifies ASAS 20 at Week 12 as the primary endpoint and gives the rule used to define a responder. It also describes missing-data handling for non-responder imputation and identifies an observed-cases analysis population.

What the record does not establish is the primary outcome result. The responder count, estimate of response, confidence interval, and statistical test are not reported in the registry record. Consequently, the size and precision of the observed response cannot be assessed. The listed secondary endpoints likewise do not establish their results, since outcome estimates are not reported.

The single-group design also limits what can be concluded. A response count among treated subjects is not a randomized comparison with another treatment or with no treatment. Even if a change from baseline were reported, a single-group design could not isolate the treatment's contribution from other influences over time. Open-label assessment is relevant context, particularly for patient-reported components, but does not show that any particular result was biased.

Safety listings describe events recorded in the study group. They do not, on their own, demonstrate causation or allow a comparison of safety with another treatment. The record's event figures should therefore be understood as descriptive observations within this study.

The study can be read as a record of the design, endpoint definitions, and selected safety and analysis details. It cannot support a quantified judgment about the primary result, its uncertainty, or a comparative treatment effect from the information reported. Those elements are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically instructive because its endpoint definition is more complete than its reported outcome information. The registry record explains how ASAS 20 classifies response across patient global assessment, pain, function, and inflammation. That definition makes clear what the primary endpoint was intended to count, while the absence of a reported result prevents assessment of the response magnitude or its precision.

The single-group design illustrates the difference between describing outcomes and estimating a comparative effect. A count of responses in a treated group can be clinically informative as a description, but without a concurrent comparator it does not answer how outcomes would differ under another treatment. This distinction is important when interpreting open-label studies and change-from-baseline measures.

The record also makes analysis populations and missing-data assumptions relevant. Non-responder imputation assigns missing visits a non-response status, whereas observed-cases analysis uses available assessments. These approaches can target different summaries when data are missing. The registry record describes the approaches but does not report results that would allow their consequences to be compared.

Finally, the registry lists many outcome measures but reports no analyses. This highlights why outcome definitions alone are not enough to evaluate a study statistically. Results, uncertainty estimates, and an account of multiplicity are needed to judge how precise and interpretable the findings are. In their absence, the design and methods can be discussed, but the trial's efficacy estimates cannot be reconstructed from the registry record.

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 most important limitation for interpreting the posted results is that the registry record does not report the primary endpoint result. It names ASAS 20 at Week 12 but gives no responder count, estimate, confidence interval, or test. Secondary outcome results are also not reported, despite the record listing multiple outcome measures.

The study is single-group and open-label, with no randomized comparator. It can describe outcomes among the study participants but cannot provide a direct estimate of how treatment outcomes compare with an alternative. Open-label status is also relevant to assessments that include patient-reported domains, although the record does not establish that this affected any particular assessment.

Some analysis details are incomplete. The arm description ends mid-sentence, so the full treatment sequence and any dose-change criteria cannot be determined. The observed-cases description also ends after referring to one subject who discontinued before an unspecified point. The timing and reason are not reported in the registry record.

The record does not report the number or reasons for missing primary endpoint observations, the study's sample-size justification, the statistical analysis plan, interim analyses, or a strategy for multiplicity. It describes non-responder imputation and an observed-cases population, but provides no results for evaluating sensitivity to these choices. These gaps limit assessment of both the trial's analysis and the precision or robustness of any outcome estimate.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis — NCT00667355.
• Registry record last updated 2012-01-26; status last verified 2012-01.
• Results first posted 2010-08-11.
• 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

NCT00667355 is a completed Phase 3, multicenter, open-label, single-group study sponsored by Abbott. It evaluated adalimumab in Japanese subjects with active ankylosing spondylitis. The record reports enrollment of 41, a study start of 2008-02, and primary completion in 2009-05.

The primary endpoint was the number of subjects achieving ASAS 20 at Week 12. The record describes subcutaneous adalimumab, including 40 mg at baseline and a regimen of 40 mg or 80 mg every other week, but the arm description is incomplete. The registry lists 19 outcome measures and reports zero analyses.

The record describes non-responder imputation and an observed-cases analysis based on 40 subjects. It lists serious and other adverse event figures, but does not report the primary efficacy result or its uncertainty. The statistical plan, sample-size justification, and multiplicity approach are not reported in the registry record.