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 A Study of MabThera (Rituximab) in Participants With Rheumatoid Arthritis Who Have Had an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARD) and/or Anti-Tumor Necrosis Factor (Anti-TNF) Therapy. (NCT00503425), a na phase 3 study. The primary outcome is Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00503425 |
| Phase | Phase 3 |
| Condition | Rheumatoid Arthritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 215 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants had active rheumatoid arthritis and an inadequate response to prior treatment with DMARDs and/or one anti-TNF alpha agent. The registry record describes a safety population of participants who received any part of an infusion of study medication.
Intervention
Participants received rituximab, identified in the record as MabThera/Rituxan. The described regimen was 1000 mg intravenously on days 1 and 15. Concomitant DMARDs, corticosteroids, NSAIDs and analgesics were permitted throughout the study period.
Comparator
There was one study group and no randomized comparator. The record lists allocation as not applicable and masking as none. The results therefore describe participants treated in this study rather than a contrast between rituximab and a control group.
Primary question
The primary endpoint counted participants with adverse events and serious adverse events from baseline through study withdrawal or follow-up, approximately 104 weeks. This is a safety-focused question. The record also lists disease-activity and bone-density outcomes, but their numerical results are not reported in the registry record.
The study addressed safety and disease activity in a population whose prior treatment had not provided an adequate response, as described by the registry record. Its design was open label and single group, so the central posted result is a description of events among treated participants. It cannot by itself establish how those events compare with what would have occurred under another treatment or without the study treatment.
The registry lists enrollment of 215 participants, while its safety population is defined by having received any part of an infusion. The primary safety results use a denominator of 209. These figures represent different record entries and should not be treated as interchangeable populations. The record does not report the numerical results for the listed secondary disease-activity outcomes, so the clinical question answered by the posted primary results is narrower than the full set of study objectives.
3. Trial Design
This was a phase 3, completed, single-group, open-label study sponsored by Hoffmann-La Roche. The registry lists the study start as 2005-06-30 and primary completion as 2013-05-26. Allocation is recorded as not applicable, masking as none, and the model as single group. There was no randomized control arm in the design described in the record.
The intervention was rituximab, listed as MabThera/Rituxan. Participants were to receive 1000 mg intravenously on days 1 and 15. The study description says participants were followed every 8 weeks through the Week 24 visit, then every 3 months for up to 18 months, with an overall study duration of 24 months (104 weeks). The anticipated time on study treatment was 2 years. After week 36, eligible participants achieving a moderate or good response under EULAR response criteria were to receive retreatment. Concomitant DMARDs, corticosteroids, NSAIDs and analgesics were allowed throughout the study period.
The registry lists enrollment of 215 and describes a target sample size of 200 in the study summary. Those entries describe enrollment and the stated target; they are not results of a comparative power calculation. The registry record does not report the rationale for the target sample size or a protocol-based sample-size justification.
Safety was assessed in participants who had received any part of an infusion of study medication. The primary endpoint covered events from baseline to study withdrawal or follow-up, approximately 104 weeks. The posted safety group has 209 participants at risk for both serious and other adverse events. No control-group estimate is available, and no masking was used to reduce participants' or investigators' knowledge of treatment assignment. The record does not report details of independent safety adjudication or a more specific assessment schedule for adverse events.
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
| Stage | Rituximab |
|---|---|
| STARTED | 215 |
| COMPLETED | 161 |
| NOT COMPLETED | 54 |
Reasons for not completing this period:
| Reason | Rituximab |
|---|---|
| Participant files lost | 6 |
| Adverse Event | 5 |
| Lack of Efficacy | 25 |
| Withdrawal by Subject | 8 |
| Lost to Follow-up | 3 |
| Death | 3 |
| Missing Data/Unknown | 4 |
Analysis population for the primary outcome, as defined in the registry: Safety population included all participants who had received any part of an infusion of study medication.
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: Intent to treat (ITT) population: All participants who had received any part of infusion of study medication. Participants who prematurely withdrew from study for any reason and for whom assessment is not performed for whatever reason were also included in ITT analysis. Due to incomplete database only 209 participants were considered for analysis.
| Characteristic | Unit | Rituximab |
|---|---|---|
| Participants analysed | 209 | |
| Age, Continuous | Years | 56.6 (SD 13.1) |
| Sex: Female, Male: Female | Participants | 146 |
| Sex: Female, Male: Male | Participants | 63 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Baseline up to study withdrawal or follow-up (Approximately 104 weeks).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with adverse events (AEs) and serious adverse events (SAEs). The registry defines an AE as any untoward medical occurrence in a participant who received study drug. An SAE was an AE associated with a specified serious outcome, including death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, or congenital anomaly; an event could also be considered serious for another significant reason.
The endpoint is a count of participants, not a count of separate event episodes. The registry explicitly states that participants counted with non-serious AEs are counted exclusive of SAEs. The posted results report 70 participants with SAEs and 176 with non-serious AEs, each among 209 participants at risk. A participant count can help readers understand how many people experienced events, but it does not describe how many events each person had, when events occurred, how long they lasted, or their relationship to treatment.
Safety endpoints are used to describe harms observed during treatment and follow-up. In an open-label, single-group study, these counts are descriptive: without a comparator, they do not estimate the difference in risk attributable to treatment. The endpoint description does not identify a causal assessment procedure. The record does not report an overall estimate with a confidence interval or a separate analysis of event timing.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary safety results report 70 participants with serious adverse events and 176 with non-serious adverse events, each out of 209 participants at risk in the rituximab group. The registry defines the safety population as participants who received any part of an infusion of study medication. The count of non-serious adverse events is exclusive of serious adverse events as specified in the endpoint description. The record does not clarify whether an individual participant could appear in both participant counts through experiencing events of both types.
These are descriptive counts from a single study group. They show that serious and non-serious events were recorded during the study period, but do not establish that rituximab caused them. Rheumatoid arthritis itself, prior and concomitant treatments, and other circumstances may also be relevant to observed events; the registry record does not provide analyses separating such influences. Because there is no randomized comparator, these results cannot estimate an excess or reduced risk relative to another treatment.
The serious-event terms listed include rheumatoid arthritis at 5.3%, chest pain at 3.8%, and pyrexia, pneumonia, syncope and pregnancy each at 1.9%. These are the listed percentages for the reported serious terms. The registry record does not specify the denominator or explain whether terms are participant-level categories, event counts, or selected terms under a particular reporting threshold. They should therefore be read as the registry's reported term percentages, not as a complete ranking of all possible harms or as a basis for calculating comparative risks.
The record lists no numerical confidence interval, p-value, adjusted estimate or model-based effect for the primary endpoint. It also does not report the death count; the death field is not populated. That is not evidence that no deaths occurred. Similarly, the registry lists secondary outcomes for disease activity and bone density, but their numerical results are not reported in the registry record. No conclusion about those outcomes can be drawn from their titles alone.
Enrollment is listed as 215, while the safety results use 209 participants at risk. The record's safety-population definition explains that the analysis includes those who received any part of an infusion, but it does not report why the enrollment and safety denominators differ. The results consequently apply to the stated safety population and follow-up description, not automatically to every enrolled participant or to other patient groups. Their precision cannot be judged from counts alone without an uncertainty estimate and fuller information about event ascertainment and missing follow-up.
9. Statistical Methods Explained
The primary safety endpoint is a participant count. In general, a count answers how many people in an analysis population experienced the specified outcome during the defined observation period. It is different from an event count, which could count repeated episodes in one person more than once. The registry describes its primary measure as the number of participants with AEs and SAEs and defines the safety population as those who received any part of an infusion.
What does a single-group count tell us?
In a single-group study, a count describes what was observed among participants receiving the study intervention. It does not provide a treatment contrast. A randomized comparison can, under its design and analysis assumptions, estimate how outcomes differ between assigned groups. This study has no randomized comparator, so the posted counts cannot show whether event frequency was higher or lower than it would have been under another treatment or no study treatment.
For a binary outcome such as whether a participant experienced an event, an analysis may also express the count relative to the number assessed. A confidence interval around such an estimate can communicate sampling uncertainty: it describes a range of values compatible with the data under the chosen statistical method. The posted primary results give counts and denominators, but the registry record does not report confidence intervals or a model-based estimate. No confidence interval or percentage should be inferred from those counts for this interpretation.
Why distinguish serious from non-serious events?
Seriousness is defined by the event's consequences or significance, not simply by how often it occurs. The registry's SAE definition includes death, hospitalization, a life-threatening experience, persistent or significant disability or incapacity, congenital anomaly, or another significant reason. The record states that the non-serious AE participant count excludes SAEs. This distinction helps readers separate the two reported categories, although the endpoint description does not provide event-level detail, severity grades, duration, or the number of events per participant.
Safety observation over an extended period can capture events occurring at different times, but a cumulative participant count does not show the timing of events or account for differing time under observation. Time-to-event methods can address timing and follow-up duration when suitable event-time data are available. The registry record does not report such an analysis for the primary safety endpoint, so the posted counts should not be interpreted as event rates per unit of time.
What does open-label mean for interpretation?
Open-label means masking was not used, as recorded for this study. In general, knowledge of treatment can influence reporting, clinical assessment, or decisions to investigate and classify symptoms. This does not establish that such influence occurred in this study. It is a design feature relevant when considering subjective outcomes and adverse-event ascertainment. The registry record does not describe blinded adjudication or a method intended to mitigate these possibilities.
The record identifies 209 participants at risk for the serious and other event counts. The population is defined by receipt of any part of an infusion. For any analysis, the denominator must correspond to the people eligible for that endpoint and observation period. Enrollment and the safety population are not necessarily the same; the record lists enrollment as 215 but does not explain the difference from the safety denominator.
How should planning calculations be read?
Any sample-size illustrations associated with the posted results are planning exercises, not results observed in this study and not the study's original design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such calculations answer a hypothetical design question: how large a future comparison might need to be under those assumptions. They do not establish that the current study had a particular power, and they do not remedy the absence of a randomized comparator.
General sample-size calculations depend on the outcome definition, assumed effect, variability or event frequency, statistical test, allocation, and desired power. Changing assumptions changes the planning result. For binary outcomes, the event probability in each planned group matters; for continuous outcomes, variability matters. The registry record does not report its own statistical sample-size justification, and the planning assumptions described for illustrations should not be presented as the protocol's plan.
Finally, a statistical analysis plan specifies matters such as endpoint definitions, analysis populations, missing-data handling, multiplicity control, and planned models. Those details are not reported in the registry record beyond the stated safety-population definition and outcome descriptions. In their absence, the participant counts can be described, but undocumented inferential procedures should not be attributed to the study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures and four analyses. It names secondary outcomes involving mean change in DAS28 at Week 24, improvement in DAS28 by greater than 1.2 at Week 24, EULAR DAS28 response at Week 24, and change in bone density score at Weeks 48 and 104. The numerical results for these outcomes are not reported in the registry record. Their presence indicates that the study addressed more than the primary safety endpoint, but the record does not explain how the analyses relate to the listed outcome measures.
When multiple outcomes or analyses are tested, the chance of at least one apparently unusual result can increase if each is assessed separately without adjustment. Methods for controlling multiplicity can include prioritizing a primary endpoint, adjusting significance thresholds, or specifying a hierarchy of tests. These are general statistical approaches, not descriptions of what this study did. A multiplicity strategy is not reported in the registry record, nor is a statistical analysis plan that would establish which comparisons were confirmatory.
The record does not report missing-data counts, reasons for missingness, or methods for handling missing outcome measurements. It also does not describe how participants who withdrew or had incomplete follow-up contributed to each analysis. The safety endpoint timeframe extends to withdrawal or follow-up, but the record does not provide event ascertainment after withdrawal or detail how follow-up loss was handled. These omissions limit assessment of whether the reported counts fully reflect the planned observation period.
The safety population is explicitly defined as participants who received any part of an infusion. The registry record does not report other analysis-population definitions for the disease-activity or bone-density outcomes. The listed enrollment of 215 and safety denominator of 209 should therefore be understood as separate entries, without inferring participant flow or reasons for exclusion that the record does not provide.
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 |
|---|---|---|---|
| Rituximab | 70 | 209 | 33.5% |
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 |
|---|---|
| Rituximab | 176 of 209 |
Most frequent serious adverse event terms
| Event term | Organ system | Rituximab |
|---|---|---|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 11 of 209 |
| Chest pain | General disorders | 8 of 209 |
| Pyrexia | General disorders | 4 of 209 |
| Pneumonia | Infections and infestations | 4 of 209 |
| Syncope | Nervous system disorders | 4 of 209 |
| Pregnancy | Pregnancy, puerperium and perinatal conditions | 4 of 209 |
| Cholelithiasis | Hepatobiliary disorders | 3 of 209 |
| Myocardial infarction | Cardiac disorders | 2 of 209 |
| Abdominal pain | Gastrointestinal disorders | 2 of 209 |
| Cellulitis | Infections and infestations | 2 of 209 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rituximab |
|---|---|---|
| Back pain | Musculoskeletal and connective tissue disorders | 28 of 209 |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 25 of 209 |
| Vitamin D deficiency | Metabolism and nutrition disorders | 22 of 209 |
| Upper respiratory tract infection | Infections and infestations | 21 of 209 |
| Headache | Nervous system disorders | 20 of 209 |
| Hypertension | Vascular disorders | 18 of 209 |
| Urinary tract infection | Infections and infestations | 15 of 209 |
| Chest pain | General disorders | 14 of 209 |
| Rash | Skin and subcutaneous tissue disorders | 14 of 209 |
| Pyrexia | General disorders | 12 of 209 |
Serious events with the highest arm-level rate: rheumatoid arthritis (5.3%), chest pain (3.8%), pyrexia (1.9%), pneumonia (1.9%), syncope (1.9%).
The serious adverse event result is 70 participants among 209 at risk in the rituximab group. The corresponding non-serious adverse event count is 176 among 209 at risk. The registry defines the safety population as participants who received any part of an infusion and states that the non-serious AE count excludes SAEs. These are counts of participants, not counts of all event episodes.
The listed serious-event terms are rheumatoid arthritis at 5.3%, chest pain at 3.8%, and pyrexia, pneumonia, syncope and pregnancy each at 1.9%. The record does not identify the denominator or the term-selection and coding rules for these percentages. They should be read as the registry's reported percentages, not as rates per person-time or as a complete inventory of serious events.
The primary timeframe runs from baseline to withdrawal or follow-up, approximately 104 weeks. The record does not report event timing, duration, severity grading, relatedness to treatment, or a separate death count. The death field is not populated, so the registry record does not report the death count. Since the study is single group and open label, these safety figures are descriptive and cannot establish comparative risk or causation.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry recorded 70 participants with serious adverse events and 176 with non-serious adverse events among 209 participants at risk in the safety population. They provide a descriptive account of safety events during the stated observation period. The registry's definitions make clear that serious events are classified by specified outcomes or significance, while the non-serious AE count excludes SAEs.
The results do not show that rituximab caused any particular event. A participant's event during a study is not by itself proof that the intervention produced it. The study has no randomized control group, and it is open label, so the reported counts do not estimate a causal difference between treatments. They also do not establish whether the event burden was greater or smaller than under usual care, another drug, or no study treatment.
The counts do not reveal how many separate episodes occurred, when events happened, how long they lasted, or whether an individual experienced more than one kind of event. The listed serious-event percentages add detail about reported terms, but the registry record does not state their denominator or selection rules. The death count is not reported in the registry record, and the absence of a populated field should not be interpreted as zero deaths.
The registry also names disease-activity and bone-density outcomes, but their numerical results are not reported in the registry record. Consequently, the safety counts cannot answer whether disease activity changed or how bone density changed. Nor can the enrollment entry of 215 be substituted for the safety denominator of 209: the record defines the safety population separately and does not explain the difference between the entries.
Overall, these data are useful as a record of observed safety outcomes in the defined treated population, within this study's follow-up. They are not a comparative effectiveness estimate, a complete accounting of every possible risk, or a basis for attributing individual events to treatment. Interpretation beyond these descriptive results would require additional outcome details, follow-up information, and a suitable comparison.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between describing safety and estimating comparative effects. A single-group study can document events that occur during treatment and follow-up, including serious events defined by clinically consequential criteria. The posted counts make the observed safety population and event categories explicit: 70 participants with SAEs and 176 with non-serious AEs among 209 at risk.
Those figures can be informative for understanding what was recorded in the study, but they do not have the interpretive force of a randomized contrast. Without a control group, the counts cannot separate events associated with the intervention from events that might also occur because of the underlying condition, prior treatment, concomitant care, or other circumstances. This limitation is especially relevant when readers are tempted to treat a treatment-period event count as a treatment effect.
The record also shows why endpoint definitions and denominators matter. The safety population is defined by receipt of any part of an infusion, and the primary endpoint counts participants rather than all event episodes. The registry lists overall enrollment separately. Reporting these distinctions helps prevent accidental mixing of enrolled participants, treated participants, and event counts.
Finally, the study demonstrates the value of separating reported observations from unavailable analyses. Secondary outcomes are named, but their numerical results are not reported in the registry record; neither a death count nor uncertainty estimates are reported. Statistical interpretation should remain proportionate to what is documented. The record supports a careful descriptive safety account, while leaving comparative, causal, and precision questions unanswered.
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 absence of a randomized comparator is a central limitation for interpreting the safety findings. The single-group, open-label design provides no concurrent control estimate, and the reported counts cannot quantify a difference in risk between treatment options. Open-label status may also be relevant to event reporting and assessment, although the registry record does not show that ascertainment was biased.
The posted primary results do not include confidence intervals, p-values, adjusted estimates, or event rates over time. Counts alone do not show their statistical precision or the timing and recurrence of events. The SAE term percentages are listed without a stated denominator or details of term selection. The death count is not reported in the registry record.
The enrollment entry is 215, while the safety denominator is 209. The record defines the safety population by receipt of any part of an infusion but does not provide participant flow or explain the difference. It also does not report missing-data amounts, follow-up completeness, reasons for withdrawal, or methods used to handle missing observations.
The registry lists secondary disease-activity and bone-density outcomes, but their numerical results are not reported in the registry record. Multiplicity procedures, a detailed statistical analysis plan, and the original sample-size justification are also not reported. These limitations restrict interpretation to the safety counts and descriptive information documented in the registry, without extending conclusions to efficacy, comparative safety, or the experience of populations not described in the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of MabThera (Rituximab) in Participants With Rheumatoid Arthritis Who Have Had an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARD) and/or Anti-Tumor Necrosis Factor (Anti-TNF) Therapy. — NCT00503425.
- Registry record last updated 2017-08-15; status last verified 2017-06.
- Results first posted 2016-06-23.
- 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
The registry record describes a completed phase 3, open-label, single-group study of rituximab in participants with active rheumatoid arthritis and an inadequate response to prior DMARDs and/or anti-TNF therapy. Enrollment is listed as 215, and the study summary gives a target sample size of 200. Participants were described as receiving 1000 mg intravenously on days 1 and 15, with follow-up extending to 24 months (104 weeks) and retreatment for eligible participants after week 36.
The primary endpoint counted participants with AEs and SAEs. In the safety population of participants who received any part of an infusion, the posted results report 70 participants with SAEs and 176 with non-serious AEs, each among 209 at risk. The study had no randomized comparator. Numerical results for the listed secondary outcomes, the death count, missing-data handling, and comparative estimates are not reported in the registry record.