A Study To Evaluate The Efficacy Of Enbrel (REGISTERED) Etanercept Over A Period Of 12 Months In The Routine Treatment Of Patients With Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis, Or Plaque Psoriasis.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study To Evaluate The Efficacy Of Enbrel (REGISTERED) Etanercept Over A Period Of 12 Months In The Routine Treatment Of Patients With Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis, Or Plaque Psoriasis. (NCT02486302), a registered phase not stated study. The primary outcome is Number of Participants With Rheumatoid Arthritis (RA) Who Achieved 28 Joint Disease Activity Score (DAS28) Less Than (<) 2.6 at Week 12.

2. Clinical Question

The study's stated clinical focus is how patients' clinical status changes during routine etanercept treatment, including whether improvement is observed after the initial 12 weeks. Its title also describes follow-up over 12 months and identifies rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and plaque psoriasis as the conditions of interest. The record lists no control group, and it does not describe treatment assignment as randomized. Accordingly, the study question is descriptive: what outcomes and treatment continuation were observed among people treated in routine care? It cannot by itself isolate a causal treatment effect from changes that might have occurred for other reasons.

There is a difference in scope between the broad treatment-goal question in the study summary and the listed primary outcome. The latter is a specific remission threshold for the rheumatoid arthritis subgroup at a particular assessment time. It should not be read as a primary measure of efficacy across all four conditions, nor as a direct test of improvement after Week 12. The registry does not report the number achieving the threshold or an estimate of the proportion that did so.

3. Trial Design

This is a prospective, multicenter, non-interventional study of etanercept in routine clinical treatment. The record describes observation over a maximum of 12 months among patients with rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, or plaque psoriasis. The study is marked completed, with enrollment of 1534. Its listed intervention is etanercept, and its arm description identifies an observation group without further description.

In a non-interventional design, treatment is not assigned by randomization for purposes of the study. Treatment decisions and the characteristics of patients receiving treatment may therefore reflect ordinary clinical practice. This can make observed outcomes relevant to describing the treated population, while also making causal comparisons difficult: factors associated with receiving treatment may also be associated with outcomes. Here, no randomized comparator is listed, and allocation information is not stated. The record explicitly cautions that the arms are not a like-for-like control comparison.

The broad study objective is to assess etanercept outcomes during routine use and to pay particular attention to patients who attain a desired treatment goal after 12 weeks. The primary outcome actually listed is the number of participants with rheumatoid arthritis whose DAS28 is less than 2.6 at Week 12. Other registry outcomes include treatment continuation and treatment-emergent adverse events at scheduled follow-up times, as well as disease activity, patient global assessment, fatigue, and pain measures. These listed outcomes span more than one disease area and assessment time.

The record does not report the protocol's detailed visit procedures, treatment rules, criteria for entering or leaving the study, or the reasons patients might discontinue treatment. It also does not report a statistical analysis plan or a sample-size justification for the study. Those details should not be inferred from the fact that enrollment and follow-up are recorded. The record lists no analysis entries. The available information therefore supports a description of the design and registered outcomes, but not a reconstruction of all operational or analytic decisions.

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: Per-protocol (PP) set=all documented participants who were treated, had at least 1 post-baseline value, AE documented and no major protocol deviation. Overall number of participants analyzed signifies participants of PP set with RA evaluable for this outcome measure.

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: Treated set included all documented participants who were treated, had at least 1 post-baseline value and had an adverse event (AE) documented.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Rheumatoid Arthritis (RA) Who Achieved 28 Joint Disease Activity Score (DAS28) Less Than (<) 2.6 at Week 12, measured over Week 12.

The listed primary outcome is the number of participants with rheumatoid arthritis who achieved a DAS28 score less than 2.6 at Week 12. DAS28 combines information from a 28-joint swollen-joint count and tender-joint count, the erythrocyte sedimentation rate, and the patient's global assessment of disease activity. The patient global assessment is recorded on a visual analogue scale, with higher values representing greater disease activity according to the registry description.

The registry defines a DAS28 less than 2.6 as remission. It also describes low disease activity as a score less than or equal to 3.2, and moderate to high disease activity as greater than 3.2 to 5.1. These categories give clinical context to the score: rather than relying on a single symptom or laboratory measure, the index combines several components into an overall disease-activity measure. A threshold-based outcome can be easy to interpret as a count of participants meeting a prespecified clinical state.

The outcome is limited to participants with rheumatoid arthritis and to the Week 12 assessment. Its analysis population is the per-protocol set, defined in the record as treated participants with at least one post-baseline value, adverse-event documentation, and no major protocol deviation; the analyzed population is further restricted to those with rheumatoid arthritis evaluable for this outcome. The number meeting the threshold, the denominator evaluated, and any estimate of uncertainty are not reported in the registry record. The listed outcome therefore defines what was intended to be counted, but the available record does not establish the observed remission frequency.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a prospective, multicenter, non-interventional study. The statistical interpretation therefore begins with the distinction between describing outcomes and estimating a causal treatment effect. General: an observational study records treatment and outcomes as they occur in practice, without random allocation by the study. Randomization can help balance known and unknown prognostic factors across groups; in an observational setting, those factors may differ between people receiving treatment and any comparison group. Since no comparator group is described in this record, the available design information supports descriptive interpretation rather than a controlled treatment-effect estimate.

What does a count endpoint tell us?

The primary endpoint is a count: participants with rheumatoid arthritis who achieved DAS28 less than 2.6 at Week 12. A count reports how many people met the endpoint, but interpretation usually also depends on the number assessed. The registry defines the analyzed population as the participants in the per-protocol set with rheumatoid arthritis who were evaluable for this outcome. Neither the endpoint count nor its denominator is reported in the registry record. Thus, no observed proportion can be stated from the available endpoint information.

General: when a study reports a proportion, its denominator identifies the group to which the proportion applies. If some enrolled participants have no evaluable measurement, a proportion among those assessed may differ from a proportion among everyone enrolled. The handling of participants without an endpoint assessment can therefore affect interpretation. The record's population definition offers a rule for who could be analyzed, but it does not report how many met that rule or how missing measurements were handled in the analysis.

How should the DAS28 threshold be understood?

The endpoint turns a continuous disease-activity score into a binary classification: meeting or not meeting the remission threshold. The registry describes DAS28 as incorporating joint counts, erythrocyte sedimentation rate, and patient global assessment. A threshold makes an outcome easier to communicate as a clinical state, but it also discards information about how far an individual score lies above or below the cutoff. Two scores on the same side of a threshold can differ, while the binary classification treats them alike for this endpoint. The record gives the threshold definition but does not report the underlying score distribution or the number on either side of it.

The study summary's treatment-goal question is broader than this endpoint. A response at Week 12 under a particular threshold should not be treated as evidence about the summary's 12- and 24-week goal proportions unless the corresponding results and definitions are available. The registry does not report enough detail to equate those questions.

What does a confidence interval add?

General: a confidence interval expresses the statistical uncertainty around an estimated quantity, such as a proportion or a difference. It gives a range of values compatible with the data under the method's assumptions; it is not a guarantee that the true value lies within that particular interval. A narrow interval usually indicates greater precision than a wide interval, but precision is not the same as freedom from bias. An interval around an observational estimate does not address confounding, selection, or measurement limitations by itself.

No confidence interval for the primary endpoint is reported in the registry record. The record also gives no primary endpoint estimate from which its precision could be described. It would therefore be inappropriate to characterize the remission frequency as precise or imprecise on the basis of this entry.

Why do analysis populations matter?

The primary endpoint uses a per-protocol population. The registry defines that set as participants who were treated, had at least one post-baseline value, had adverse events documented, and had no major protocol deviation. It then limits the outcome population to those with rheumatoid arthritis who were evaluable for this measure. Such restrictions can describe a particular subset of enrolled participants, rather than every person enrolled. General: excluding participants after enrollment can change the composition of the analyzed group, particularly if reasons for missing data or deviations are related to prognosis or treatment experience.

The record also lists treated-set and per-protocol-set versions of treatment continuation and adverse-event outcomes. Those population labels should not be assumed to have identical membership. The registry does not give counts for all the analysis populations, a flow of participants through follow-up, or the statistical rules used to handle missing assessments. Comparisons across outcomes or populations therefore require caution.

What do the planning illustrations mean?

General: a sample-size calculation estimates how much information a future study might need under stated assumptions. The record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect; for time-to-event outcomes, the illustration concerns total events, while other illustrations concern participants per arm. These are planning assumptions, not a description of the study's actual design or an observed measure of power.

The study itself is described as non-interventional, with an observation group and no stated allocation. Accordingly, hypothetical equal allocation between arms in a planning calculation should not be mistaken for evidence that this study randomized or assigned participants equally. The record does not report a protocol-based sample-size justification, and the planning approach does not replace one. General: a planning estimate also depends on its assumed effect and model; if those assumptions do not match a future study, the estimate may not describe the information that study will need.

What does over-dispersion mean in general?

General: some count outcomes vary more than a simple statistical model expects. This extra variability is called over-dispersion. Ignoring it can make uncertainty appear smaller than it is. Appropriate modeling may need to allow for variability beyond the simplest assumptions. The registry record does not report a model for the primary endpoint or identify over-dispersion as an issue in its analysis. No conclusion about the use or adequacy of such a model can be made from the information recorded.

The registry lists no analysis entries. The detailed model specifications, covariate adjustments, interim analyses, and statistical decision rules are not reported in the registry record. General statistical explanations cannot fill in those study-specific omissions.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Etanercept")
n      <- c(794)
events <- c(194)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Etanercept  794  194  24.4  21.5  27.6  21.6  27.5  21.6  27.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 52 outcome measures, including outcomes assessed at different follow-up times and measures covering disease activity, treatment continuation, adverse events, fatigue, pain, and patient global assessment. Considering many outcomes can raise a multiplicity issue: if many statistical tests are conducted, the chance of at least one apparently unusual result may increase. General: a prespecified analysis plan can identify primary and secondary outcomes and explain whether or how multiplicity is addressed. The registry record does not report a multiplicity adjustment or a strategy for interpreting results across outcomes.

The record identifies the Week 12 rheumatoid arthritis DAS28 remission count as the primary outcome measure, while the brief summary describes a broader treatment-goal question at 12 and 24 weeks. The relationship between that summary and the listed primary outcome is not explained in enough detail to resolve the difference. The record also lists no analysis entries, and statistical methods for secondary outcomes are not reported in the registry record.

Missing-data handling is not reported in the registry record. The per-protocol definition requires a post-baseline value and adverse-event documentation, but the record does not give the number excluded by these criteria, the reasons for missing outcome measurements, or the methods used to address missingness. General: results among participants with observed measurements can differ from results that would have been obtained if all enrolled participants had complete follow-up, especially if missingness is associated with health status or treatment continuation.

The primary outcome is restricted to the per-protocol participants with rheumatoid arthritis evaluable for the endpoint. Other listed measures use treated-set or per-protocol labels. Their population sizes and the details of any population-specific analyses are not reported. The registry record therefore does not support a full assessment of multiplicity, missing-data bias, or consistency across analysis populations.

12. 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: condition aggravated (1.1%), osteoarthritis (0.8%), intervertebral disc protrusion (0.3%), drug ineffective (0.3%), bronchitis (0.3%).

The registry reports serious adverse events for the etanercept group as 151 participants affected, with 1465 at risk. For other adverse events, it reports 606 participants affected, also with 1465 at risk. The record separately reports 5 deaths. These are counts from the study record and should be interpreted as descriptive observations during follow-up.

The listed serious-event terms include condition aggravated at 1.1%, osteoarthritis at 0.8%, intervertebral disc protrusion at 0.3%, drug ineffective at 0.3%, bronchitis at 0.3%, and pneumonia at 0.3%. These percentages are reported terms in the registry record; they do not establish that an event was caused by etanercept. A safety listing may include events occurring during treatment without demonstrating a causal relationship.

General: a count of people affected is not the same as a count of all event episodes, since one person may experience more than one event. The record labels the outcome as the number of participants with events, but does not provide event-level detail or enough information to characterize timing, duration, or causal assessment. The record has no described comparator, so these figures cannot show whether serious or other adverse events were more frequent than they would have been under a different treatment or without treatment. They should not be interpreted as a comparative risk estimate.

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

The registry record establishes that a prospective, multicenter, non-interventional study followed etanercept use in routine care across rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and plaque psoriasis. Its listed primary outcome is a Week 12 count of participants with rheumatoid arthritis achieving DAS28 less than 2.6. It also lists outcomes on treatment continuation, adverse events, disease activity, patient global assessment, fatigue, and pain.

However, the observed result for the primary outcome is not reported in the registry record. The record does not state how many participants with rheumatoid arthritis met the threshold, how many were evaluated, or an uncertainty interval for the result. The study's broad stated interest in attaining a treatment goal at 12 and 24 weeks is not accompanied by a reported result in the information. Consequently, the registry entry does not establish the frequency of remission or whether the stated treatment goals were attained.

The observational design also limits what results could mean even if outcome estimates were available. Without random assignment or a described comparator group, changes during routine treatment cannot be attributed solely to etanercept. Other influences, including patient characteristics and changes in care, could contribute to observed outcomes; the registry record does not report an analysis capable of separating those influences.

The safety counts describe participants affected by events recorded during the study. They are not estimates of treatment-caused harm, nor do they establish comparative safety. The record's event terms and counts should be interpreted in the context of routine clinical observation and the absence of a control comparison.

Thus, the study is best read as an observational description of intended outcomes and recorded events in routine practice, not as a randomized test of efficacy. The record supplies useful details about the endpoint definition and analysis population, but its missing endpoint results and unreported statistical plan leave important questions unanswered. No medical conclusion about treatment should be drawn from the outcome definition or descriptive safety counts alone.

14. Why This Trial Matters Statistically

This study is statistically notable for the gap between a broad clinical question and a more narrowly defined primary outcome. The stated focus concerns treatment goals over follow-up and particular attention to later attainment after 12 weeks, whereas the listed primary measure counts rheumatoid arthritis participants meeting a DAS28 remission threshold at Week 12. Clear alignment between a study objective, outcome definition, time point, and analysis population is important because each element determines what a result can answer. The registry does not report a result that would resolve the broad question.

The record also illustrates why design labels matter. Prospective follow-up can document outcomes as they occur, but non-interventional observation does not provide the protection against confounding that random allocation can offer. In the absence of a described comparator, an observed outcome is not a comparative treatment effect. That distinction remains essential even when outcomes are clinically meaningful or follow-up is extensive.

Analysis population definitions are another important statistical feature. The primary outcome applies to a per-protocol group with rheumatoid arthritis evaluable for the measure, rather than automatically to every enrolled participant. Because the record does not report the number analyzed or the number meeting the endpoint, readers cannot evaluate the size and precision of the result. Missing-data and population-flow details would also help assess how representative the analyzed participants are of the enrolled population.

Finally, multiple outcomes and time points create a need for transparent statistical planning. The record lists many measures but does not report a multiplicity strategy or detailed analysis plan. These omissions do not imply that a particular method was or was not used; they mean that the registry record does not permit evaluation of that issue. The study is a useful example of how endpoint definitions, population selection, missing outcomes, and design limitations shape the interpretation of clinical data.

15. 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 immediate limitation is that the result for the listed primary endpoint is not reported in the registry record. The count meeting the DAS28 remission threshold, the number evaluated, and any uncertainty estimate are absent. The entry therefore permits discussion of the outcome definition but not an assessment of its observed frequency.

The study has no described randomized comparator, and allocation is not stated. The registry explicitly indicates that the arms are not a like-for-like control comparison. Any outcome observed during routine treatment would be vulnerable to differences in patient characteristics, clinical decisions, and other factors that cannot be assessed from the available record. A causal comparison with another treatment or with no treatment is not supported.

The broad study summary and the listed primary endpoint have different scopes. The summary addresses desired treatment goals at 12 and 24 weeks, while the listed primary measure is a Week 12 remission count for rheumatoid arthritis. The record does not explain how the broad goal definition relates to the specified DAS28 threshold or provide results for the broader question.

The primary analysis population is restricted to per-protocol participants with rheumatoid arthritis evaluable for the outcome. The record does not report the size of that population, the number excluded, or a participant flow through follow-up. Missing-data methods, detailed statistical models, covariate adjustments, and a multiplicity strategy are not reported in the registry record. The entry also does not report a protocol-based sample-size justification.

Safety reporting is likewise limited for causal interpretation. Counts are reported without a comparator, and the record does not provide enough detail to assess event timing, recurrence, or attribution. These limitations are specific to the information recorded and should not be replaced by assumptions about how the study may have been conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study To Evaluate The Efficacy Of Enbrel (REGISTERED) Etanercept Over A Period Of 12 Months In The Routine Treatment Of Patients With Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis, Or Plaque Psoriasis. — NCT02486302.
• Registry record last updated 2019-06-24; status last verified 2019-03.
• Results first posted 2019-06-24.
• 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.

19. Record Summary

The registry record describes a completed, prospective, multicenter, non-interventional study of etanercept during routine treatment for rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, or plaque psoriasis. Enrollment was 1534, and the study followed patients for a maximum of 12 months. No randomized comparator is described.

The listed primary outcome is the number of participants with rheumatoid arthritis achieving DAS28 less than 2.6 at Week 12, analyzed in an evaluable per-protocol population. The record does not report the primary outcome result, its denominator, or an uncertainty estimate. It lists 52 outcome measures and no analysis entries.

Safety information includes 151 participants affected by serious adverse events among 1465 at risk, 606 affected by other adverse events among 1465 at risk, and 5 deaths. These are descriptive counts, not comparative treatment-effect estimates. The detailed statistical plan, missing-data methods, and multiplicity strategy are not reported in the registry record.