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 Substudy - Low Dose of Abatacept in Subjects With Rheumatoid Arthritis (NCT00989235), a randomized phase 3 study. The primary outcome is Time to Disease Relapse Through Month 12 (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00989235 |
| Phase | Phase 3 |
| Condition | Rheumatoid Arthritis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 108 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bristol-Myers Squibb |
| Results posted | Yes |
2. Clinical Question
Population
Participants had rheumatoid arthritis and were enrolled in a low-dose abatacept substudy. The study summary says they had achieved remission, defined as a DAS28-ESR score < 2.6, at Day 701 of study IM101023. The registry record reports an enrollment of 108. Further eligibility details and the number entering the substudy after meeting the remission criterion are not reported in the registry record.
Intervention
The low-dose group received abatacept 5 mg/kg. The registry record describes this as a randomized, double-blind substudy. Further details about dosing schedules, concomitant therapies, and treatment duration are not reported in the registry record.
Comparator
The comparator group received abatacept 10 mg/kg. The registry lists abatacept as the drug in both intervention entries; it does not describe additional arm-level treatment details in the arm descriptions.
Primary question
The primary endpoint asks how the cumulative percentage of disease-relapse events changed over Months 1 through 12 in the two dose groups. Relapse included additional DMARD therapy, 2 or more courses of high-dose steroids, return to abatacept 10 mg/kg as rescue medication, or DAS28-CRP scores of at least 3.2 at 2 consecutive visits.
3. Trial Design
The registry describes a randomized, double-blind, parallel-group substudy with an enrollment of 108. Its official title identifies it as a phase 3B, multicenter substudy; the registry phase category is Phase 3. The two named groups received abatacept 5 mg/kg or abatacept 10 mg/kg. The arm descriptions themselves are blank, so the registry record does not provide additional information about how treatment was administered or how other therapies were handled.
The study summary frames the substudy as an exploratory clinical evaluation of reducing abatacept dose in participants who had achieved remission at Day 701 of study IM101023. Remission is described as DAS28-ESR < 2.6. This means the question concerns participants selected after attaining remission in the parent study, rather than an unselected population beginning treatment for rheumatoid arthritis. Details about the parent study’s treatment history and the eligibility process for this substudy are not reported in the registry record.
The primary outcome follows relapse through Month 12. The registry’s outcome description defines relapse using several possible events, including treatment escalation or specified disease-activity findings at consecutive visits. The primary outcome population is described as the number randomized; the number at risk is defined as the number at risk at the end of a specified month. The record lists a start date of 2007-04, a primary completion date of 2009-10, and a completed status.
Although the title mentions abatacept plus methotrexate and methotrexate, the substudy intervention entries identify abatacept in both groups, and the arm descriptions do not clarify other treatment components. The exact treatment regimen in this substudy is therefore 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.
Before assignment: Of the 433 participants who completed the main study (IM101-023 NCT00122382), 108 enrolled in the sub-study.
Overall Study
| Stage | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| STARTED | 58 | 50 |
| Number Rescued to Open-Label Treatment | 4 | 4 |
| Number Completing Double-Blind Treatment | 51 | 41 |
| COMPLETED | 55 | 44 |
| NOT COMPLETED | 3 | 6 |
Reasons for not completing this period:
| Reason | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) |
|---|---|---|
| Death | 0 | 1 |
| Adverse Event | 0 | 1 |
| Lack of Efficacy | 1 | 0 |
| Withdrawal of Consent | 1 | 1 |
| Desire to Become Pregnant | 1 | 0 |
| Randomized by Mistake | 0 | 2 |
| Lost to Follow-up | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Number of participants analyzed=number of participants randomized. n=number of participants at risk at the end of a specified month.
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.
| Characteristic | Unit | Abatacept (10 mg/kg) | Abatacept (5 mg/kg) | Total |
|---|---|---|---|---|
| Participants analysed | 58 | 50 | 108 | |
| Age Continuous | years | 50.1 (SD 11.5) | 51.1 (SD 13.4) | 50.6 (SD 12.3) |
| Sex: Female, Male: Female | Participants | 44 | 41 | 85 |
| Sex: Female, Male: Male | Participants | 14 | 9 | 23 |
| Race/Ethnicity, Customized: Unknown | participants | 2 | 0 | 2 |
| Race/Ethnicity, Customized: White | participants | 49 | 46 | 95 |
| Race/Ethnicity, Customized: Black | participants | 2 | 0 | 2 |
| Race/Ethnicity, Customized: Asian | participants | 2 | 2 | 4 |
| Race/Ethnicity, Customized: Other | participants | 3 | 2 | 5 |
| Weight | kg | 72.9 (SD 14.7) | 73.8 (SD 16.0) | 73.4 (SD 15.3) |
| Disease Activity Scores Using C-reactive Protein (DAS 28 [CRP]) | units on a scale | 2.1 (SD 0.6) | 2.1 (SD 0.6) | 2.1 (SD 0.6) |
6. Primary Endpoint
The registry lists the primary outcome as Time to Disease Relapse Through Month 12 (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse), measured over Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of Events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is time to disease relapse through Month 12, reported as the Kaplan-Meier cumulative percentage of relapse events. It combines the timing of a first qualifying relapse with the proportion of participants who experience such an event over follow-up. The registry describes monthly time points from Month 1 through Month 12.
Relapse is a composite outcome: an event is counted if additional DMARD therapy is given, if 2 or more courses of high-dose steroids are given, if the participant returns to abatacept 10 mg/kg as rescue medication, or if DAS28-CRP is at least 3.2 at 2 consecutive visits. These components represent different ways the study defined a loss of disease control or a change in treatment. The definition is important because an event could arise from a clinical score or from a treatment decision; the primary endpoint does not isolate those pathways.
In general, Kaplan-Meier methods estimate the cumulative occurrence of an event over time while accounting for participants whose follow-up ends before an event is observed. The registry says life tables using Kaplan-Meier cumulative percentages were used. The monthly pattern can convey when events accumulated, not only whether an event occurred by the end of follow-up. The outcome values and group comparisons are not reported in the registry record, so the endpoint’s observed magnitude and precision cannot be described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The substudy’s central statistical question is whether relapse accumulated differently over time among participants assigned to abatacept 5 mg/kg or 10 mg/kg after achieving remission. The registry identifies randomization and double masking, features intended to support a fair comparison and reduce the influence of treatment knowledge on assessments or care. They do not, on their own, establish the size or precision of any observed difference.
The outcome is a time-to-event composite followed through Month 12. A cumulative percentage at a given month represents the estimated proportion who have experienced a qualifying relapse by that point, according to the study definition. The registry describes the method and event definition but does not report the monthly estimates, event counts, confidence intervals, or a statistical comparison between dose groups. The result’s direction, magnitude, and uncertainty are therefore not reported in the registry record.
Interpretation also depends on the relapse definition. Additional DMARD therapy, high-dose steroid courses, rescue return to 10 mg/kg, and consecutive DAS28-CRP scores at least 3.2 are not identical events. A composite can capture several forms of relapse or response to worsening disease, but it can conceal which component contributed most. Component-specific outcome results are not reported in the registry record.
The study summary calls this an exploratory substudy and describes its purpose as evaluating the clinical impact of lowering the dose in participants who had achieved remission at Day 701. The findings, if reported, would apply most directly to this selected remission population and this study’s relapse definition. They would not by themselves describe outcomes for all people with rheumatoid arthritis or for people who had not attained remission. The registry record does not report a sample-size justification, a target effect, or details of a confirmatory analysis plan.
Separate safety entries list participants affected by serious and other adverse events in the short-term groups and in an open-label group. Those counts are not substitutes for the primary time-to-relapse comparison. The open-label group is distinct from the two short-term group entries, and the registry’s figures do not establish a causal safety contrast. More detail on reading those counts appears in the safety discussion.
Overall, the available registry information specifies the question, design, endpoint, and event definition but not the primary outcome results. Without the estimates and their uncertainty, it is not possible to characterize how much relapse occurred in either group or how precisely the groups differed.
9. Statistical Methods Explained
What does a time-to-event endpoint represent?
The primary outcome is framed as time to disease relapse through Month 12. Unlike a simple count of participants with an event at one fixed visit, a time-to-event approach uses information about when relapse occurs during follow-up. The registry lists monthly time points from Month 1 through Month 12 and describes the output as a Kaplan-Meier cumulative percentage of events.
General explanation: Kaplan-Meier estimation is a way to estimate event occurrence over time when participants may have different lengths of observation. A participant who has not had the event by their last observed follow-up can contribute information up to that point, after which their later event status is unknown. This is commonly called censoring. The estimate relies on assumptions about censoring and the quality of event ascertainment. The registry identifies Kaplan-Meier life tables but does not report censoring details or checks of those assumptions.
How is relapse defined?
The registry defines disease relapse as any of four specified circumstances: additional DMARD therapy, 2 or more courses of high-dose steroids, return to abatacept 10 mg/kg as rescue medication, or a DAS28-CRP score of at least 3.2 at 2 consecutive visits. In general, a composite endpoint can capture multiple clinically relevant routes to an event. Its interpretation depends on the components and their relative frequency. A composite result alone does not show which component occurred most often. Component-level counts or estimates are not reported in the registry record.
What does randomization contribute?
The study is described as randomized, double-blind, and parallel-group. General explanation: Random assignment is used to reduce systematic differences between treatment groups at the point of assignment, while masking can limit the influence of treatment knowledge on participant reporting, clinical decisions, and outcome assessment. A parallel design assigns participants to a group and follows them within that group rather than having every participant receive each study treatment in sequence. These design features support interpretation of a comparison, but do not eliminate all sources of uncertainty. Details of the randomization procedure, concealment, and masking implementation are not reported in the registry record.
What can be learned from the number at risk?
The endpoint description says the number analyzed is the number randomized and defines the number at risk as the number at risk at the end of a specified month. A risk set is the group still being observed and eligible to have the event occur at that point. General explanation: The size of that group matters because later estimates may be based on fewer participants, and therefore can be less precise. The actual monthly risk-set counts and event estimates are not reported in the registry record.
How should uncertainty be assessed?
General explanation: A confidence interval describes a range of values compatible with the observed data under the analysis assumptions. It communicates precision, not the probability that a particular treatment effect is true. For a time-to-event comparison, a group estimate and an interval around it would help readers assess both the event pattern and its uncertainty. The registry record does not report confidence intervals, a hazard ratio, or another comparative estimate for the primary endpoint. No statistical significance conclusion can be drawn from the endpoint description alone.
Why can over-dispersion matter for other outcomes?
General explanation: Count outcomes can vary more than a simple statistical model assumes, a feature called over-dispersion. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. The primary endpoint is described as a Kaplan-Meier time-to-event outcome, not as a count model. The registry record does not give enough analysis detail to determine which methods were used for the other outcome measures or whether over-dispersion was assessed.
What does the record say about planning?
The record identifies 108 participants enrolled, but a sample-size justification and the assumptions used in the original study design are not reported in the registry record. In general, a sample-size calculation depends on a target effect, variability or event assumptions, significance level, power, and design features. A planning illustration based on an observed effect, when available, is not the trial’s original justification and is not observed power. The primary outcome has multiple time points and is not reduced to one comparison in the statistical summary. The registry record does not report a single primary comparison estimate or a basis for interpreting a planning calculation.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 20 outcome measures and 19 analyses. The primary endpoint itself is reported across Months 1 through 12, and the secondary outcomes cover several kinds of disease activity, treatment escalation, rescue medication, and therapy modification. Having multiple outcomes or time points creates multiple opportunities to observe apparently notable patterns by chance. Whether and how that concern was addressed depends on the prespecified analysis plan.
The registry record does not report a multiplicity adjustment, a hierarchy of endpoints, or a detailed statistical analysis plan. It also does not identify which analyses were confirmatory and which were exploratory beyond describing the substudy as exploratory in the summary. Without those details, the family of comparisons intended for formal inference and the interpretation of any individual p-value are not reported in the registry record. The outcome results and p-values are also not reported in the registry record.
The primary outcome description defines the analysis population as the number randomized, which is the registry’s stated population for this endpoint. It does not explain how participants with missing visits, incomplete follow-up, protocol deviations, or unavailable outcome assessments were handled. Although Kaplan-Meier methods generally accommodate censoring, the timing and reasons for censoring, and any assumptions or sensitivity analyses, are not reported in the registry record.
The record defines the monthly number at risk but does not provide the risk-set values. It does not report imputation methods, missing-data rates, or comparisons of missingness between groups. These omissions limit assessment of how much incomplete follow-up could affect the estimates and whether the reported analysis population corresponds to all randomized participants at each time point.
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 |
|---|---|---|---|
| Abatacept 5mg/kg (ST) | 3 | 50 | 6.0% |
| Abatacept 10mg/kg (ST) | 3 | 58 | 5.2% |
| Abatacept 10mg/kg (Open-Label) | 2 | 8 | 25.0% |
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 |
|---|---|
| Abatacept 5mg/kg (ST) | 17 of 50 |
| Abatacept 10mg/kg (ST) | 18 of 58 |
| Abatacept 10mg/kg (Open-Label) | 7 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Abatacept 5mg/kg (ST) | Abatacept 10mg/kg (ST) | Abatacept 10mg/kg (Open-Label) |
|---|---|---|---|---|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 1 of 50 | 0 of 58 | 1 of 8 |
| Rheumatoid Arthritis | Musculoskeletal and connective tissue disorders | 2 of 50 | 0 of 58 | 0 of 8 |
| Leukopenia | Blood and lymphatic system disorders | 1 of 50 | 0 of 58 | 0 of 8 |
| Neutropenia | Blood and lymphatic system disorders | 1 of 50 | 0 of 58 | 0 of 8 |
| Cardiopulmonary Failure | Cardiac disorders | 1 of 50 | 0 of 58 | 0 of 8 |
| Cholelithiasis | Hepatobiliary disorders | 0 of 50 | 0 of 58 | 1 of 8 |
| Appendicitis | Infections and infestations | 0 of 50 | 1 of 58 | 0 of 8 |
| Endocarditis | Infections and infestations | 1 of 50 | 0 of 58 | 0 of 8 |
| Diabetes Mellitus Inadequate Control | Metabolism and nutrition disorders | 1 of 50 | 0 of 58 | 0 of 8 |
| Acquired Claw Toe | Musculoskeletal and connective tissue disorders | 0 of 50 | 1 of 58 | 0 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Abatacept 5mg/kg (ST) | Abatacept 10mg/kg (ST) | Abatacept 10mg/kg (Open-Label) |
|---|---|---|---|---|
| Upper Respiratory Tract Infection | Infections and infestations | 6 of 50 | 3 of 58 | 1 of 8 |
| Nasopharyngitis | Infections and infestations | 3 of 50 | 3 of 58 | 1 of 8 |
| Hypertension | Vascular disorders | 4 of 50 | 2 of 58 | 1 of 8 |
| Influenza | Infections and infestations | 2 of 50 | 3 of 58 | 0 of 8 |
| Headache | Nervous system disorders | 2 of 50 | 3 of 58 | 0 of 8 |
| Bronchitis | Infections and infestations | 1 of 50 | 3 of 58 | 0 of 8 |
| Conjunctivitis | Eye disorders | 2 of 50 | 0 of 58 | 1 of 8 |
| Diarrhoea | Gastrointestinal disorders | 1 of 50 | 0 of 58 | 2 of 8 |
| Fatigue | General disorders | 3 of 50 | 0 of 58 | 0 of 8 |
| Back Pain | Musculoskeletal and connective tissue disorders | 3 of 50 | 0 of 58 | 0 of 8 |
Serious events with the highest arm-level rate: cholelithiasis (12.5%), osteoarthritis (12.5%), rheumatoid arthritis (4.0%), leukopenia (2.0%), neutropenia (2.0%).
The registry lists serious adverse event figures for three group entries. In the short-term abatacept 5mg/kg group, 3 of 50 participants at risk were affected by serious adverse events, and 17 of 50 were affected by other adverse events. In the short-term abatacept 10mg/kg group, the corresponding figures are 3 of 58 for serious adverse events and 18 of 58 for other adverse events. The open-label abatacept 10mg/kg group lists 2 of 8 participants affected by serious adverse events and 7 of 8 affected by other adverse events.
These are separate adverse-event categories as recorded; the registry figures do not establish that the categories are mutually exclusive, nor do they show the timing, duration, severity distribution, or relationship to treatment for each event. The open-label group is not the same design context as the two short-term entries, so the figures should not be read as a randomized comparison with those groups. Death counts are not reported in the registry record.
The record also lists serious-event terms with percentages, including Cholelithiasis at 12.5%, Osteoarthritis at 12.5%, Rheumatoid Arthritis at 4.0%, Leukopenia at 2.0%, Neutropenia at 2.0%, and Cardiopulmonary Failure at 2.0%. The group and denominator associated with these term percentages are not reported in the registry record, so they cannot be directly reconciled with the group counts above. These safety entries describe recorded events and do not by themselves establish that a treatment caused an event.
12. What the Result Does, and Does Not, Mean
The registry record gives a clearly defined comparison: abatacept 5 mg/kg versus abatacept 10 mg/kg in a randomized, double-blind substudy of participants who had achieved remission. It also describes a composite relapse endpoint followed through Month 12 and identifies the principal kinds of events that count as relapse. These details help establish what the study set out to examine.
The posted information does not include the primary outcome estimates, the numbers of relapse events by group, the monthly cumulative percentages, confidence intervals, or a between-group statistical comparison. Consequently, the available record does not establish how often relapse occurred, whether one group had more events, or how precise any difference was. No conclusion about the direction or size of a treatment contrast can be drawn from the endpoint definition alone.
Even if a group difference were available, the clinical meaning would depend on its magnitude, uncertainty, timing, and which components of the composite produced it. Treatment changes and disease-activity measurements are distinct components, and a composite result would not identify their separate contributions unless component results were also reported. The registry record does not report those component-specific results.
The study summary describes the substudy as exploratory and limits its context to participants who reached remission at Day 701 of study IM101023. It therefore addresses a selected population and should not be assumed to describe every person with rheumatoid arthritis, people who did not reach remission, or other treatment settings. The registry record also does not report enough detail about the substudy regimen or missing-data handling to broaden interpretation beyond the stated design and endpoint.
The listed adverse-event counts provide descriptive information for specified group entries, but they do not replace the efficacy endpoint or establish causation. Overall, the registry record identifies the intended question and methods while leaving the primary comparative result and its precision not reported in the registry record.
13. Why This Trial Matters Statistically
This substudy raises a useful statistical question about maintaining a remission state after a dose change. Rather than focusing only on a single disease-activity measurement, it defines relapse through both treatment-related events and repeated disease-activity scores. That approach makes the endpoint responsive to several manifestations of worsening or treatment escalation, while also making the composite’s individual components important to interpretation.
The endpoint is time-based, so the timing of events matters as well as their occurrence. Kaplan-Meier cumulative percentages can describe how relapse accumulates over follow-up, while numbers at risk help readers understand how much observed follow-up contributes at later months. This is a different statistical perspective from comparing only the final number of participants with an event.
The design also highlights a population-specific inference. Participants entered the substudy after achieving a stated remission threshold at Day 701 of the parent study. Statistical results from such a selected group would answer a focused question about that setting; they would not automatically generalize to people at other stages of rheumatoid arthritis or to those who had not attained remission.
At the same time, interpretation requires the actual estimates and their uncertainty. Randomization and masking support a controlled comparison, but they cannot substitute for reported event counts, cumulative estimates, confidence intervals, or analysis details. With those primary outcome results not reported in the registry record, the statistical value of the registry entry is chiefly in clarifying the study question, endpoint definition, and limits on what can be inferred from the available 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 registry record does not report the primary outcome results, including event counts, monthly cumulative percentages, or a direct comparison of the dose groups. It also does not report confidence intervals or other measures of precision. This prevents assessment of the magnitude, direction, and uncertainty of the principal contrast.
The relapse definition combines events that may arise through different processes: additional DMARD therapy, high-dose steroid courses, rescue return to abatacept 10 mg/kg, and repeated DAS28-CRP scores at least 3.2. Component-level results are not reported in the registry record, so the contribution of each component cannot be evaluated. The record also does not describe adjudication procedures for relapse events.
Although randomization, double masking, and a parallel design are stated, details of allocation, masking implementation, follow-up schedules, and treatment administration are not reported in the registry record. The arm descriptions are blank, and the exact role of other therapies in the substudy is not specified. The study summary identifies a remission population from the parent study, but further eligibility and selection details are not reported in the registry record.
The outcome description defines the analysis population as the number randomized and gives a definition for the number at risk. However, monthly risk-set counts, censoring patterns, missing outcome data, and missing-data methods are not reported in the registry record. The statistical analysis plan, multiplicity handling, and sample-size justification are also not reported. These gaps limit assessment of robustness, the intended inferential framework, and the extent to which the design was planned around the endpoint.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Substudy - Low Dose of Abatacept in Subjects With Rheumatoid Arthritis — NCT00989235.
- Registry record last updated 2011-06-21; status last verified 2011-06.
- Results first posted 2011-06-03.
- 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 completed randomized, double-blind, parallel-group substudy enrolled 108 participants with rheumatoid arthritis. Its summary describes evaluating abatacept dose reduction among participants who had achieved remission, defined as DAS28-ESR < 2.6, at Day 701 of study IM101023. The two listed groups received abatacept 5 mg/kg or 10 mg/kg.
The primary outcome was time to disease relapse through Month 12, expressed as Kaplan-Meier cumulative percentages. Relapse included additional DMARD therapy, 2 or more high-dose steroid courses, return to abatacept 10 mg/kg as rescue medication, or DAS28-CRP of at least 3.2 at 2 consecutive visits. The record lists 20 outcome measures and 19 analyses.
The record lists a start date of 2007-04 and a primary completion date of 2009-10. It does not report the primary outcome estimates, their uncertainty, a detailed statistical analysis plan, or a sample-size justification. The listed adverse-event counts are descriptive and include a separate open-label group.