An Open Label Study for Participants With Rheumatoid Arthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open Label Study for Participants With Rheumatoid Arthritis (NCT01215942), a randomized phase 3 study. The primary outcome is Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period.

2. Clinical Question

3. Trial Design

The registry describes a Phase 3 study, while its official title calls it a Phase 3b study. It was randomized, parallel-group and open-label, meaning the registry records no masking. Enrollment was 1086. The listed intervention was LY2127399, given in two dosing schedules: 120 milligrams every 4 weeks or 90 mg every 2 weeks.

The study included two periods. During Period 1, participants entering from BCDO or BCDV could receive unblinded treatment for up to 240 weeks; those entering from BCDM could receive treatment for up to 168 weeks. Period 2 was a 48-week post-treatment follow-up. These are maximum durations described in the registry summary, not a statement that every participant completed the full period.

For participants starting treatment after receiving placebo immediately before enrollment, the arm descriptions specify a 240 mg loading dose for the 120-milligram schedule and a 180 mg loading dose for the 90 mg schedule. The descriptions also refer to the earlier studies when outlining duration. The available wording for those descriptions is incomplete, so further schedule details are not reported in the registry record.

The registry gives a start date of 2011-06, a primary completion date of 2014-02 and a status of terminated. It does not report the reason for termination. Although the record labels the allocation as randomized, details of the sequence generation, concealment, allocation ratio and assignment process are not reported. The record lists 17 outcome measures and 0 analysis entries.

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: Study consisted of a Treatment Period of up to 240 weeks for participants (pts) who enrolled from Studies H9B-MC-BCDO (BCDO) (NCT01202760) and H9B-MC-BCDV (BCDV) (NCT01202773) or up to 168 weeks for pts who enrolled from Study H9-MC-BCDM (BCDM) (NCT01198002). Discontinued pts were followed in Post-Treatment Follow-Up Period for up to 48 weeks.

Treatment Period

Reasons for not completing this period:

Post-Treatment Follow-Up Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All enrolled participants.

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: All enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period, measured over up to 84.4 weeks during treatment period.

The primary outcome counts participants who had treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) during treatment. The stated timeframe is up to 84.4 weeks during the treatment period. The primary-outcome population is all enrolled participants.

A TEAE was defined as an event that first occurred or worsened in severity on or after the first injection and before study termination. The listed AESIs were infection, injection-site reactions, malignancy, major adverse cardiovascular events, allergy and hypersensitivity, depression, suicide or self-injury, and pregnancy. The record defines major adverse cardiovascular events through a list of adjudicated event types, including cardiovascular death, myocardial infarction, stroke, hospitalization for specified cardiovascular conditions and revascularization procedures.

This endpoint is used to describe safety events observed during treatment. General statistical context: a participant count answers how many people were recorded with an event, but does not by itself describe how long each person was exposed or establish that treatment caused the event. Nor is a count alone a comparison of risk between groups. The registry points readers to its Reported Adverse Events module for summaries of SAEs and other non-serious adverse events, regardless of causality. The record does not report an inferential analysis of the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this? The primary outcome is a participant count. The registry reports how many participants had TEAEs, SAEs and AESIs, with participants at risk shown separately for each treatment-period and follow-up group. A participant count differs from an event count: one participant may experience more than one event, but the count of participants records whether a person was affected. The outcome description does not report event rates adjusted for time at risk.

What does a treatment-emergent event mean? In this study, a TEAE was defined as an event that first occurred or worsened in severity on or after the first injection and before study termination. This timing rule identifies events occurring or worsening during the specified period; it does not, by itself, show that treatment caused them. The registry's AESI list identifies event types of particular interest, while SAE is presented as a separate safety category. The registry does not give a separate SAE definition in the primary-outcome description.

How should the group counts be read? Each count should be read alongside its corresponding number at risk and period. For example, the treatment-period serious-event figures are 30 of 414 for the 120 mg group and 57 of 672 for the 90 mg group. The follow-up figures refer to different at-risk counts. These counts are not direct measures of comparative treatment effect. A formal comparison would need a specified estimand, a statistical model or test, and uncertainty estimates. Such an analysis is not reported in the registry record.

General statistical context: a confidence interval describes the range of effect estimates compatible with the data and the method's assumptions. It helps communicate precision, rather than merely whether an estimate crosses a significance threshold. No confidence interval is reported for these primary-outcome counts. A p-value, if reported, would address compatibility with a null hypothesis under specified assumptions; it would not measure the probability that a treatment works or the probability that chance alone produced the results. No p-value or primary-outcome test is reported.

Why can event counts be difficult to compare? Participants may have different lengths of observation, particularly when treatment duration can vary according to the earlier study from which they enrolled. The primary outcome's stated timeframe is up to 84.4 weeks during treatment, while the design summary describes longer possible treatment periods. The record does not explain how the primary-outcome timeframe was applied to individual participants. General statistical context: when observation time varies, counts alone can give an incomplete comparison; rates or time-to-event methods may account for exposure time, but the registry record does not report such an analysis for this outcome.

The record identifies the study as randomized and parallel-group. In general, random allocation can support comparisons by balancing measured and unmeasured characteristics on average, but that benefit depends on how allocation was conducted and on appropriate analysis. The allocation procedure and analysis method are not reported. The open-label design means that masking was absent according to the record. General statistical context: lack of masking may affect reporting and assessment, especially where event classification involves judgment. It does not make the recorded counts unusable, but it is relevant when interpreting them.

The registry lists 17 outcome measures and 0 analysis entries. It does not report a statistical analysis plan, a model for the primary outcome, a multiplicity procedure, or confidence intervals. The record also does not report interim analyses or a sample-size justification. General statistical context: a prespecified analysis plan helps clarify which outcomes and comparisons were intended, and how uncertainty and multiple testing were to be handled. Without those details, the posted counts can be described, but the inferential strength of any group comparison cannot be assessed from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including the primary safety outcome and secondary measures such as ACR20 response, DAS28-CRP, EULAR-28 response, SF-36 scores, joint counts, pain assessment and global disease-activity assessment. It contains 0 analysis entries. A statistical analysis plan, outcome hierarchy, or procedure for controlling multiplicity is not reported in the registry record.

General statistical context: when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase. Prespecifying a primary outcome and defining how secondary outcomes will be interpreted can help distinguish confirmatory findings from exploratory ones. Because no analysis details are reported, it is not possible to determine which comparisons were planned, whether adjustments were made, or how any secondary results should be ranked.

Handling of missing outcome data, withdrawals, censoring and incomplete follow-up is not reported in the registry record. The primary outcome specifies all enrolled participants as its population, but this does not explain how participants without complete safety information were handled. The record also does not give analysis populations for the secondary outcomes or describe exclusions from analyses.

General statistical context: missingness can affect estimates when the likelihood of data being absent is related to participants' health, treatment or outcomes. Different assumptions about missing data can lead to different conclusions, so the handling approach matters. Without a reported method or a breakdown of missing observations, the potential effect of incomplete information cannot be evaluated from this record.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: prostate cancer (0.8%), rheumatoid arthritis (0.7%), atrial fibrillation (0.7%), osteoarthritis (0.5%), cardiac failure congestive (0.5%).

During treatment, the 120 mg group lists 30 of 414 participants with serious adverse events and 130 of 414 with other adverse events. The 90 mg group lists 57 of 672 with serious adverse events and 251 of 672 with other adverse events. During follow-up, the corresponding figures are 15 of 368 and 47 of 368 for the 120 mg group, and 28 of 591 and 71 of 591 for the 90 mg group.

These are participant counts; they do not show the number of separate events or how many participants experienced events in both categories. The treatment and follow-up periods are separate reporting periods and should not be combined as though they were one observation window. The registry does not report an adjusted comparison between dosing groups, exposure-adjusted rates, or uncertainty estimates for these figures.

The serious-event terms listed most often include prostate cancer at 0.8%, rheumatoid arthritis at 0.7%, atrial fibrillation at 0.7%, osteoarthritis at 0.5%, cardiac failure congestive at 0.5%, and sepsis at 0.5%. The registry does not report a causal attribution for these terms in this summary. Death counts are not reported in the registry record.

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

The posted safety results describe how many participants in each listed group were recorded with serious and other adverse events during treatment and follow-up. They also identify several serious-event terms and their reported percentages. These are descriptive findings. They do not, on their own, establish that an event was caused by LY2127399 or that one dosing schedule has a different safety profile from the other.

The registry identifies a randomized design, but does not report the randomization procedure or a comparative analysis of the posted counts. No confidence intervals or p-values for the primary outcome are reported. The group counts therefore cannot show how precisely any difference between groups has been estimated, and they do not establish statistical significance. The record also does not report a reason for the study's terminated status.

The primary outcome is safety-focused. Although secondary outcome measures include clinical response, disease activity, function, joint counts and patient assessments, analysis entries for those measures are not reported. Their presence in the outcome list is not evidence of a particular efficacy result. The record does not report estimates that would support conclusions about changes in those measures.

General statistical context: an observed count is one part of the evidence, while interpretation also depends on outcome definitions, time at risk, missing data, allocation, assessment and uncertainty. Here, treatment durations could differ according to the earlier study of enrollment, and the record does not explain the individual observation times used for the safety summaries. That limits direct comparison of raw counts.

The information supports a description of what the registry records, not a recommendation about treatment. It does not establish benefit, lack of benefit, or a causal safety effect. A fuller evaluation would require analysis methods and results not reported in the registry record, along with the broader clinical and safety evidence.

13. Why This Trial Matters Statistically

This study is statistically notable as a long-term, open-label safety study with participants entering from earlier studies and with treatment duration dependent on the source study. The registry describes a treatment period of up to 240 weeks for participants from BCDO or BCDV and up to 168 weeks for participants from BCDM, followed by a 48-week post-treatment follow-up. This makes the distinction between treatment and follow-up counts important when reading the safety summaries.

The primary outcome is expressed as counts of participants with several types of events rather than as one comparative effect estimate. That format is useful for describing recorded safety experience, but interpretation of differences requires clarity about denominators, time at risk, event definitions and analytic methods. The record reports at-risk counts, yet does not report exposure-adjusted comparisons or uncertainty estimates for the primary outcome.

The study is labeled randomized, but the registry does not describe the assignment procedure. It is also open-label. General statistical context: randomization and masking address different sources of bias. Randomization can help balance baseline characteristics, while masking can reduce the influence of treatment knowledge on assessment and reporting. The absence of masking is especially relevant to interpretation of outcomes that depend on judgment.

The registry's 17 listed outcome measures span safety and several aspects of rheumatoid arthritis response and patient-reported status, but it records 0 analysis entries. This distinction matters: an outcome being named in a registry is not the same as a reported estimate, a prespecified statistical comparison, or evidence of a result. The record's limitations leave the descriptive safety counts interpretable while restricting what can be concluded about comparative effects.

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 registry record gives the study status as terminated but does not report why it was terminated. It does not describe the randomization sequence, allocation concealment, allocation ratio or participant assignment process. Although the study is labeled randomized, those details would be relevant to assessing the basis for a group comparison.

The study was open-label, with masking listed as none. The record does not explain whether adverse events were assessed by blinded reviewers, how events were coded, or how disagreements in event classification were handled. It also does not report a comparative analysis, confidence intervals or p-values for the primary outcome. Death counts are not reported in the registry record.

Participants came from BCDO, BCDV or BCDM, and the maximum treatment duration depended on that source. The primary safety timeframe is described as up to 84.4 weeks during treatment, while the design summary describes longer possible treatment periods. How the safety timeframe was applied to each participant is not reported. This makes it difficult to interpret raw counts as comparisons with equivalent observation time.

Missing-data methods, withdrawals, completeness of follow-up, analysis populations beyond the stated primary population, interim analyses and sample-size justification are not reported. The record lists 17 outcomes but no analysis entries or multiplicity approach. Consequently, the posted information supports a descriptive account of the recorded events, but provides limited information for judging precision, bias, or the strength of comparative conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Open Label Study for Participants With Rheumatoid Arthritis — NCT01215942.
• Registry record last updated 2018-06-11; status last verified 2018-05.
• Results first posted 2018-06-11.
• 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

This randomized, parallel-group, open-label Phase 3 study evaluated LY2127399 in participants with rheumatoid arthritis who entered from BCDO, BCDV or BCDM. Enrollment was 1086. The record describes 120 milligrams every 4 weeks and 90 mg every 2 weeks, with treatment duration depending on the earlier study and a 48-week post-treatment follow-up. The status is terminated; the reason is not reported in the registry record.

The primary outcome counted participants with TEAEs, SAEs and AESIs during treatment, with a stated timeframe of up to 84.4 weeks. The record lists 17 outcome measures and 0 analysis entries. Safety counts are reported for treatment and follow-up, but comparative estimates, uncertainty intervals, missing-data methods and the statistical analysis plan are not reported.