This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for An Extension Study to WA19977 in Patients With Active Polyarticular-Course Juvenile Idiopathic Arthritis (NCT01575769), a na phase 3 study. The primary outcome is Percentage of Participants With Adverse Events (AEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01575769 |
| Phase | Phase 3 |
| Condition | Juvenile Idiopathic Arthritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 41 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Patients from Poland and Russia with polyarticular-course juvenile idiopathic arthritis who completed the WA19977 study. The extension enrolled 41 participants; the primary outcome specifies the safety population.
Intervention
RoActemra/Actemra (tocilizumab), described in the study summary as 8 mg/kg every 4 weeks. The anticipated time on study treatment was 104 weeks.
Comparator
There was no separate comparator group. The registry identifies a single-group study with no masking and no allocation to comparison arms. These results therefore do not provide a randomized, like-for-like treatment contrast.
Primary question
The primary outcome was the percentage of participants with adverse events, from baseline to 12 weeks after the last actual study medication, for a timeframe described as up to 101 weeks. The registry defines adverse events broadly, including unfavorable signs, symptoms, or diseases associated with treatment regardless of whether a treatment relationship was judged to exist. It also specifies serious adverse events, severe adverse events, and events of special interest. In practical terms, the question is how often adverse events were reported among participants receiving tocilizumab during the extension’s safety observation period. The registry lists efficacy outcomes as secondary measures, including response thresholds, disease activity, and joint measures, but their results are not reported in the registry record.
3. Trial Design
This was a Phase 3, interventional, open-label extension study of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis. It was designed for patients from Poland and Russia who had completed the global, multinational WA19977 trial. The registry describes a single-group model, no masking, and allocation as not applicable. The study therefore has no concurrent control arm in the record, and its findings are descriptive rather than a randomized comparison between treatments.
The registry lists 41 participants as enrolled. The study summary describes tocilizumab at 8 mg/kg every 4 weeks and anticipates 104 weeks on study treatment. That anticipated duration is not the same as the observed duration for each participant. The primary outcome’s timeframe is baseline through 12 weeks after the last actual study medication, described as up to 101 weeks. Individual exposure and follow-up durations are not reported in the registry record.
The study status is terminated. The reason for termination is not reported in the registry record, so the status alone does not establish why the study ended or whether the planned follow-up was completed. The primary outcome focuses on adverse events in the safety population. Listed secondary outcomes include JIA ACR response thresholds at specified follow-up points, inactive disease, clinical remission, and changes in joint measures. Although the record lists 23 outcome measures, it reports no analyses for them. The design can describe the safety observations recorded for this extension cohort, but it cannot establish how those observations compare with outcomes under an alternative treatment or no treatment.
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: Participants who completed Visit 33 (Week 104) of the core study WA19977 (NCT00988221) with at least juvenile idiopathic arthritis (JIA) American College of Rheumatology (ACR) 30 clinical response were eligible to continue the study therapy within this long-term extension study in Russia and Poland.
Overall Study
| Stage | Tocilizumab |
|---|---|
| STARTED | 41 |
| COMPLETED | 0 |
| NOT COMPLETED | 41 |
Reasons for not completing this period:
| Reason | Tocilizumab |
|---|---|
| Adverse Event | 1 |
| Study terminated by sponsor | 40 |
Analysis population for the primary outcome, as defined in the registry: Safety population
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: Safety Population included all participants who entered the study, took at least one dose of study drug, and with at least one safety follow-up, regardless of premature withdrawal.
| Characteristic | Unit | Tocilizumab |
|---|---|---|
| Participants analysed | 41 | |
| Age, Continuous | years | 12.0 (SD 4.45) |
| Sex: Female, Male: Female | Participants | 33 |
| Sex: Female, Male: Male | Participants | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Adverse Events (AEs), measured over Baseline to 12 weeks after last actual study medication (up to 101 weeks).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with adverse events during the stated observation period: baseline through 12 weeks after the last actual study medication, up to 101 weeks. The registry defines an adverse event as an unfavorable and unintended sign, symptom, or disease associated with treatment, regardless of whether it was considered treatment-related. Worsening pre-existing conditions and certain laboratory or clinical test findings that led to a treatment change or discontinuation were also reported as adverse events.
The endpoint is used to describe the frequency of reported safety events during exposure and follow-up. The record separately defines serious adverse events by outcomes such as death, life-threatening events, hospitalization, persistent or significant disability, congenital anomaly, or medical significance. Severe events are defined by inability to work or perform normal daily activity. These classifications describe different aspects of an event and should not be treated as interchangeable.
Because the primary measure is a percentage, its interpretation depends on the safety population and the number of participants with an event. The registry identifies the safety population and reports event counts, but does not report an inferential analysis or confidence interval for the primary endpoint. The figures therefore describe observed reports; they do not by themselves estimate a comparative treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports that 3 of 41 participants in the tocilizumab group were affected by serious adverse events. It also reports 15 of 41 for other adverse events. These counts describe events in the extension cohort; they are not a comparison with a control group. The record lists multiple injuries, decreased neutrophil count, and proteinuria among the leading serious adverse-event terms, each reported as 2.4%. The death field is null, which means a death count is not reported in that field; it should not be interpreted as a recorded zero.
These observations need to be read in light of the study design. Participants entered the extension after completing WA19977, and all received the intervention described in the registry. Without a concurrent comparator, the event counts cannot show whether an event was more or less common than it would have been under another treatment or without treatment. The open-label design also means treatment and outcome assessment were not masked, although the registry record does not describe how this might have affected event reporting.
The endpoint covers a period from baseline through 12 weeks after the last actual study medication, with the maximum timeframe described as up to 101 weeks. The planned treatment duration was 104 weeks, but that anticipated duration does not establish the actual exposure or follow-up received by each participant. The reason the study was terminated and the completeness of follow-up are not reported in the registry record.
The registry lists efficacy outcomes, including JIA ACR response thresholds, inactive disease, clinical remission, and joint measures. Their results are not reported in the registry record, and the record lists 0 analyses. Consequently, the available posted results support a description of reported adverse-event counts and selected serious-event terms, not a statistical assessment of efficacy or of differences between treatments. No p-values, confidence intervals, adjusted estimates, or statistical tests are reported in the registry record. The counts should be interpreted as observations from this specific extension cohort, not as proof of causation or as a complete account of risk in other populations.
9. Statistical Methods Explained
What does a percentage with an event describe?
For a binary outcome such as whether a participant experienced an adverse event, the basic descriptive measure is the proportion of participants with the event among those assessed for that outcome. The registry reports the safety population and adverse-event counts. A proportion communicates how frequent an event was in that observed group; it does not describe the timing of the event, its duration, or whether it was caused by treatment. The primary outcome is stated as a percentage, but the record does not report an inferential analysis for it.
Event classification also matters. The registry defines adverse events broadly and says they include serious and non-serious events. Seriousness is based on specified consequences, including death, life-threatening events, hospitalization, disability, congenital anomaly, or medical significance. Severity has a separate definition based on inability to work or perform normal daily activity. A serious event is not automatically synonymous with a severe event, and the reported categories should be interpreted using the registry’s stated definitions.
Why does a single-group design limit interpretation?
A single-group extension can describe outcomes among participants receiving the study intervention, but it does not estimate a randomized contrast against another group. In a comparative trial, a treatment contrast helps distinguish outcomes between assigned groups under the trial’s design. Here, allocation is not applicable and there is no like-for-like control arm. Thus, the event counts cannot determine whether the frequency of an event differs from what would have occurred under an alternative treatment or without treatment. This is a general limitation of uncontrolled outcome data, not a conclusion about the cause of any individual event.
The extension population is also selected: participants had completed WA19977 and were from Poland and Russia. As a general matter, an extension cohort may differ from people who did not enter or complete the preceding study. The registry does not report details that would allow assessment of the extent or consequences of such selection.
What do uncertainty measures add?
In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical procedure. It helps convey the precision of an estimate, rather than only its central value. For an event proportion, uncertainty can remain substantial when the amount of information is limited, even if a point estimate appears clear. The registry record does not report a confidence interval for the primary endpoint or for the adverse-event counts, so their statistical precision cannot be assessed from the posted results. No inferential method or test is reported.
The record lists 0 analyses. It therefore does not provide an adjusted analysis, a model-based estimate, a hypothesis test, or a reported p-value for the outcomes described. The absence of such results does not establish that an effect is absent; it means the registry record does not report an analysis from which a treatment effect or its uncertainty could be evaluated.
How should planning illustrations be understood?
General sample-size calculations describe how much information a hypothetical design might require under stated assumptions. The planning illustration associated with the study uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it considers detecting a stated fraction of an observed effect. Such assumptions describe an illustration, not this extension’s actual single-group design. Any listed sample sizes are planning illustrations, not observed power, evidence that the study was adequately powered, or a record of the study’s own design justification. The registry does not report a sample-size justification or statistical analysis plan.
Over-dispersion is a general issue when outcome variability exceeds what a statistical model assumes. It can make standard errors too small and confidence intervals too narrow if the model does not account for the extra variation. The registry record does not report a model for these outcomes or an assessment of over-dispersion, and the primary endpoint is presented as a binary event measure. It would therefore be inappropriate to attribute a particular modeling approach or variance adjustment to this study.
Overall, the reported figures are descriptive. The registry record does not report the inferential procedures, uncertainty estimates, or adjustment methods needed for a more formal statistical interpretation.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 23 outcome measures, including several JIA ACR response thresholds, inactive disease, clinical remission, and changes in joint measures across follow-up points. When many outcomes or time points are examined, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures are used to manage that issue when formal hypothesis testing is planned. Whether such procedures are needed, and which approach is appropriate, depends on the prespecified aims and analysis plan. Multiplicity handling is not reported in the registry record.
The record lists 0 analyses and does not report p-values, confidence intervals, or results for the listed efficacy outcomes. There is therefore no reported set of statistical tests from which to determine whether multiplicity adjustment was applied or how it would affect interpretation. A formal statistical analysis plan is not reported in the registry record.
Missing-data methods are also not reported in the registry record. The listed outcome time points do not establish that every participant contributed data at every visit, nor do they reveal how incomplete follow-up was handled. The study status is terminated, but the reason, participant-level completion, and completeness of outcome collection are not reported. The planned treatment duration of 104 weeks should not be taken to mean every participant had that duration of exposure or observation.
The primary endpoint names the safety population, but the record does not describe further analysis-population rules or missing-event assumptions. These gaps limit assessment of how the reported counts relate to all enrolled participants and how observations after treatment discontinuation were handled. Without reported methods for missing data, multiplicity, and analysis populations, the results remain descriptive registry findings rather than a complete account of a prespecified inferential analysis.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Tocilizumab | 3 | 41 | 7.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tocilizumab | 15 of 41 |
Most frequent serious adverse event terms
| Event term | Organ system | Tocilizumab |
|---|---|---|
| Multiple injuries | Injury, poisoning and procedural complications | 1 of 41 |
| Neutrophil count decreased | Investigations | 1 of 41 |
| Proteinuria | Renal and urinary disorders | 1 of 41 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tocilizumab |
|---|---|---|
| Pharyngitis | Infections and infestations | 6 of 41 |
| Upper respiratory tract infection | Infections and infestations | 5 of 41 |
| Bronchitis | Infections and infestations | 4 of 41 |
| Neutropenia | Blood and lymphatic system disorders | 3 of 41 |
Serious events with the highest arm-level rate: multiple injuries (2.4%), neutrophil count decreased (2.4%), proteinuria (2.4%).
The serious adverse-event figures report 3 of 41 participants affected in the tocilizumab group. The registry also reports 15 of 41 for other adverse events. These are counts within the study group, not comparisons against another treatment. Multiple injuries, decreased neutrophil count, and proteinuria are listed among the leading serious adverse-event terms, each at 2.4%.
The endpoint definitions should guide interpretation. An adverse event was counted regardless of whether it was considered related to treatment. Seriousness reflects the specified medical consequences in the registry definition, while severity refers to inability to work or perform normal daily activity. Those terms do not have interchangeable meanings. The registry also identifies events of special interest, including serious infections, gastrointestinal perforations and related events, malignant neoplasms, and other listed categories; the record does not provide additional counts for those categories in the posted results.
The death field is null, so a death count is not reported in that field; null should not be read as zero. Without a comparator, uncertainty estimates, and fuller information on exposure and follow-up, the counts cannot establish relative risk, causation, or the likelihood of an event in a different population.
12. What the Result Does, and Does Not, Mean
The results describe adverse events recorded among participants in a single-group, open-label extension of tocilizumab treatment. The registry reports serious adverse events affecting 3 of 41 participants and other adverse events affecting 15 of 41. It also names several serious-event terms at 2.4% each. These figures are useful as descriptive observations about the cohort and the reporting period specified for the safety outcome.
They do not establish that tocilizumab caused any particular event. The primary adverse-event definition includes events regardless of whether they were considered treatment-related. The absence of a control group also means the figures cannot show whether event frequency was higher or lower than under another treatment or no treatment. No inferential analyses or uncertainty estimates are reported in the registry record, so the precision of these observations is not quantified there.
The record also does not report results for the listed efficacy outcomes. The secondary measures include response thresholds and indicators of disease activity, but their presence in the outcome list is not evidence of a particular clinical result. Similarly, an anticipated treatment duration of 104 weeks is not evidence that all participants completed that duration; actual participant-level exposure and follow-up are not reported.
The study’s terminated status does not explain why it ended. In the absence of that context, complete follow-up information, and comparative analyses, the posted data should be understood narrowly: they describe reported safety events in this extension cohort, not a definitive estimate of treatment effect or a guarantee about outcomes for other patients. They do not support a causal comparison, an efficacy conclusion, or a generalization to populations beyond those represented in the study.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of what an extension study can and cannot establish. It follows participants who completed WA19977 and records safety observations during continued treatment. Such a design can add descriptive information about events observed over a longer period than a short initial treatment phase might capture. The registry’s adverse-event definitions and stated follow-up timeframe also make clear that safety outcomes depend on how events are defined and over what period they are collected.
At the same time, the single-group, open-label structure places firm limits on inference. Without a concurrent comparator, an event frequency cannot be interpreted as a treatment contrast. Selection into an extension after completing a prior study can also affect which participants contribute observations; the record does not report enough information to quantify that selection. These are important considerations when readers distinguish descriptive safety data from comparative evidence.
The record lists a range of secondary outcomes, including response measures and joint assessments, but reports 0 analyses. This distinction is statistically important: listing outcomes does not provide results, uncertainty, or evidence of a treatment effect. The record also does not report missing-data methods, multiplicity handling, a statistical analysis plan, or a sample-size justification. The planning assumptions should not be mistaken for the design or performance of this single-group extension.
For biostatisticians and clinical researchers, the study illustrates why outcome definitions, analysis populations, comparison groups, follow-up completeness, and uncertainty estimates are central to interpretation. The posted adverse-event counts add descriptive context, but the absence of reported inferential results and a control group means the evidence answers a narrower question than a comparative trial would.
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.
Several features of this record constrain interpretation. First, the study is open-label and single-group, with no control arm. The adverse-event counts cannot be used to estimate a comparative treatment effect or to distinguish events associated with treatment from events that would have occurred otherwise. The registry’s definition also counts adverse events regardless of treatment relationship.
Second, this was an extension for patients from Poland and Russia who completed WA19977. The findings therefore describe this selected extension cohort and should not automatically be generalized to all patients with polyarticular-course juvenile idiopathic arthritis. The registry does not report information that would quantify how selection into the extension affected the enrolled group.
Third, the study is listed as terminated, but the reason for termination is not reported in the registry record. The planned treatment duration of 104 weeks and the primary endpoint timeframe of up to 101 weeks do not establish the actual exposure, follow-up, or completion status of each participant. Participant-level follow-up completeness and missing-data handling are not reported.
Fourth, although 23 outcome measures are listed, the record reports 0 analyses and no results for the listed efficacy outcomes. The statistical analysis plan, multiplicity procedures, confidence intervals, and inferential methods are not reported in the registry record. The death field is null, which does not supply a death count. Finally, the reported event counts and selected terms do not provide a complete account of event timing, duration, or participant-level patterns. These limitations leave the posted results as descriptive safety information rather than a comparative or fully analyzed evaluation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Extension Study to WA19977 in Patients With Active Polyarticular-Course Juvenile Idiopathic Arthritis — NCT01575769.
- Registry record last updated 2018-02-09; status last verified 2017-08.
- Results first posted 2016-01-07.
- 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.
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18. Record Summary
This Phase 3, open-label extension enrolled 41 patients from Poland and Russia with polyarticular-course juvenile idiopathic arthritis who completed WA19977. It evaluated tocilizumab, described as 8 mg/kg every 4 weeks, in a single-group design. The study is listed as terminated; the reason is not reported in the registry record.
The primary outcome was the percentage of participants with adverse events in the safety population, from baseline through 12 weeks after the last actual study medication, up to 101 weeks. The registry reports serious adverse events affecting 3 of 41 participants and other adverse events affecting 15 of 41. Several serious-event terms are listed at 2.4% each. The death field is null.
Although the registry lists 23 outcome measures, it reports 0 analyses. Results for the listed efficacy outcomes, inferential methods, uncertainty estimates, missing-data methods, and multiplicity procedures are not reported in the registry record. The posted results are descriptive and do not provide a randomized comparison.