A Study to Evaluate the Safety of Rituximab Retreatment in Subjects With Systemic Lupus Erythematosus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety of Rituximab Retreatment in Subjects With Systemic Lupus Erythematosus (NCT00381810), a na phase 3 study. The primary outcome is Percentage of Participants With at Least 1 Serious Adverse Event.

2. Clinical Question

The study description also refers to evaluating efficacy and reassessing response at 12 months. However, the registry lists one outcome measure, the serious-adverse-event endpoint, and does not report an efficacy result. The primary question is therefore about the safety outcome recorded during this retreatment extension, not whether rituximab was more effective than another option. Because participants had to have been in the earlier study, the enrolled group represents that defined extension population rather than all people with systemic lupus erythematosus.

3. Trial Design

This was a Phase II/III, open-label, multicenter, single-arm extension study of rituximab retreatment in participants with moderate to severe systemic lupus erythematosus who had previously enrolled in Protocol U2971g. The registry records enrollment of 31 participants. Allocation is listed as not applicable, consistent with the absence of separately assigned comparison arms. Participants and investigators were not masked.

The rituximab regimen was 1000 mg intravenously twice, with the infusions 14 days apart at study entry and again 6 months later. Before each study-drug infusion, participants were to receive methylprednisolone 100 or 125 mg intravenously, acetaminophen 1000 mg orally, and diphenhydramine 50 mg orally. The study description says retreatment was scheduled every 6 months over the course of 1 year, with response reassessed at 12 months.

The primary outcome concerns the percentage of participants with at least one serious adverse event from baseline through the end of the study, up to 52 weeks. The registry defines serious events by clinical consequences, including death, a life-threatening event, hospitalization, significant disability, birth defect, or an event considered medically significant by the investigator.

The record lists the study status as terminated. It records a start date of 2006-06-22 and a primary completion date of 2008-07-31, but does not report why the study was terminated. The planned sample size, reasons for the enrollment total, and whether the scheduled regimen was completed by each participant are 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.

Treatment and Safety Follow-up

B Cell Follow-up

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With at Least 1 Serious Adverse Event, measured over Baseline to the end of the study (up to 52 weeks).

The primary endpoint is the percentage of participants who had at least one serious adverse event during the period from baseline to the end of the study, up to 52 weeks. It is a participant-level binary outcome: each participant either experienced at least one event meeting the registry’s seriousness definition or did not. The definition includes events with major consequences, such as death, life-threatening illness, hospitalization, significant disability, or birth defect, as well as events the investigator considers medically significant.

This type of endpoint is used to describe the occurrence of serious harm during a study period. It can capture a range of clinically important events rather than focusing on one specific diagnosis. Counting participants with at least one event also differs from counting every event: a participant with more than one serious event still contributes once to the participant-level endpoint. That is a general feature of this kind of measure.

The registry’s safety results report 11 participants affected among 31 at risk. The endpoint percentage itself is not reported in the registry record, and no confidence interval is reported. The definition indicates what qualifies as serious, but the record does not provide further detail about event adjudication or how events were attributed to treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a participant-level binary endpoint: whether a participant had at least one serious adverse event. The results are given as counts of participants at risk and affected. This makes the observed safety information straightforward to describe, but it does not by itself provide an estimate of comparative treatment effect. No inferential analyses are listed in the registry record.

What does a binary outcome represent?

A binary outcome classifies each participant into one of two categories for the defined observation period. For this endpoint, the categories are having at least one serious adverse event or having none recorded. The unit is the participant, not the event. If one person experiences multiple serious events, the person still counts once in the primary participant-level endpoint. Event listings may nevertheless contain more than one category for a participant.

The reported count of 11 affected participants among 31 at risk gives the reader the underlying observed numbers. A percentage can be useful for communicating a binary outcome, but the registry record does not report the endpoint percentage or an uncertainty interval. No recalculated estimate is needed to interpret the count, and no additional percentage should be inferred from it in this description.

Why does the single-arm design matter?

In a randomized comparison, treatment groups can be compared using an analysis plan that accounts for how participants were assigned and how outcomes were measured. This extension had one treatment group, with allocation listed as not applicable. Its result is therefore a description of events in the rituximab-retreatment group. It cannot separate treatment effects from the underlying disease, participants’ prior treatment and study experience, other care, or chance variation. Those are general limitations of interpreting an uncontrolled safety series.

Open-label conduct means participants and investigators were not masked to treatment assignment. A single-arm study has no competing assigned treatment to mask against, and the registry gives no details about blinded outcome review. The record does not report a comparative statistical model, adjustment strategy, or hypothesis test. These features should not be filled in by assumption.

What do confidence intervals and tests add?

In general, a confidence interval conveys the uncertainty around an estimate under the assumptions of the statistical method used. A hypothesis test evaluates a specified statistical contrast under a stated model. Neither is reported for this endpoint in the registry record. In a one-group study, a test would also need a clearly stated reference value or comparison to answer a defined inferential question; no such analysis is listed. The absence of these statistics means the posted count can be described, but its statistical precision and compatibility with a particular benchmark cannot be assessed from this record.

How should the sample-size planning illustration be read?

The planning illustration is not the study’s sample-size justification and is not observed power. It uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not evidence that the extension actually randomized participants to two arms. The actual study is single-arm, and the registry does not report a design rationale or a planned sample-size calculation.

In general, planning estimates depend on the assumed effect, statistical model, allocation, and outcome variability. A planning illustration can show how sample requirements change under stated hypothetical assumptions, but it cannot repair the lack of a comparator in the observed trial. It also cannot be interpreted as the probability that the study detected an effect after it was conducted. No sample-size justification, observed-power calculation, or interim-analysis plan is reported in the registry record.

What remains unspecified?

The registry does not report an analysis population definition, handling of missing outcomes, censoring rules, or a strategy for participants who did not complete follow-up. It also does not report a confidence interval method or the statistical plan for any efficacy assessment. These omissions matter because participant availability and outcome ascertainment can affect the interpretation of a safety proportion. Without those details, the results should be read as the registry’s descriptive counts, with no additional assumptions about analysis conduct.

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("Rituximab 1000 mg")
n      <- c(31)
events <- c(11)
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  Rituximab 1000 mg  31  11  35.5  19.2  54.6  21.1  53.1  21.1  53.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the percentage of participants with at least one serious adverse event, and lists no analyses. No multiplicity adjustment or testing hierarchy is reported in the registry record. Since no inferential analyses are listed, there is no reported set of hypothesis tests from which to assess control of false-positive findings. The serious-event terms are descriptive listings and should not be treated as separate confirmatory tests.

Missing-data handling is not reported in the registry record. The safety results identify 31 participants at risk, but the record does not explain whether all enrolled participants contributed complete follow-up through the end of the study, how incomplete observation was handled, or whether outcome status was unavailable for any participant. No assumptions about those procedures can be made from the reported denominator alone.

The analysis population is also not defined. The record does not state whether the primary endpoint used all enrolled participants, participants who received any study drug, or another defined group. It does not report a protocol-specific rule for classifying participants with interrupted treatment or incomplete follow-up. The posted safety counts can be described using the denominator reported, but they should not be assigned to an unreported analysis-population definition.

Although the study description mentions reassessment of response at 12 months, the registry does not list an efficacy analysis among its reported analyses. The handling of repeated assessment, missing response data, or multiplicity across efficacy outcomes is therefore not reported in the registry record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lobar pneumonia (6.5%), systemic lupus erythematosus (6.5%), cardiac failure congestive (3.2%), angina pectoris (3.2%), enteritis (3.2%).

The safety record reports 11 participants with at least one serious adverse event among 31 at risk. It separately reports that 31 participants had other adverse events. The serious-event listings include Lobar Pneumonia and Systemic Lupus Erythematosus at 6.5% each, and Cardiac Failure Congestive, Angina Pectoris, Enteritis, and Vomiting at 3.2% each.

These figures describe reported events in the study group; they do not establish that rituximab caused an event. A single-arm study has no concurrent untreated or alternative-treatment group for estimating how the occurrence compares under another treatment strategy. Serious adverse events are defined by consequences or investigator judgment, while the listed terms identify event categories. The same participant may contribute to more than one category, so term percentages should not be combined as if each participant had only one event.

The record does not report a death count, nor does it give an uncertainty interval for the serious-event result. Neither missing item should be interpreted as a zero count or as evidence of precise estimation. The registry’s terminated status does not state a reason for termination.

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

The posted result documents serious adverse events in 11 participants among the 31 listed as at risk during follow-up. It also records other adverse events in all 31 participants at risk. These are descriptive safety findings from an open-label, single-arm extension study of scheduled rituximab retreatment. They characterize the participants included in this record and the observation period described, which extended from baseline to the end of the study, up to 52 weeks.

The result does not show how the same participants would have fared under a different treatment, without retreatment, or outside the study. No concurrent comparator was included, and the registry lists no inferential analysis. The event counts therefore cannot quantify a relative risk or establish that retreatment caused any specific event. The fact that the study involved participants previously enrolled in another protocol also means the group was defined by prior study participation; it should not automatically be treated as representative of every person with systemic lupus erythematosus.

The serious-event categories give some detail about reported event types, but they do not provide full event histories or an independent causal assessment. The registry does not report a death count, confidence interval, or efficacy result. The study description’s reference to efficacy assessment at 12 months does not substitute for an outcome result. The reason for the terminated status is also not reported.

These limits do not make the observed counts irrelevant. They identify the kinds of events recorded and the number of participants represented in the registry’s safety summary. The appropriate interpretation is descriptive and specific to this extension study. It does not establish the frequency that would occur in another group, the comparative safety of another regimen, or an efficacy conclusion.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a safety description and a comparative treatment analysis. It reports serious adverse events in a defined group receiving scheduled retreatment, but it does not include a randomized comparator. The count of affected participants can be communicated directly, yet a count alone cannot answer whether event occurrence differs from another treatment strategy.

The distinction between participant-level outcomes and event categories also matters. The primary endpoint concerns participants who experienced at least one serious event, while the safety listing includes specific event terms and percentages. A participant may experience multiple events, so term-level figures and the participant-level endpoint answer different descriptive questions. Treating the terms as disjoint categories could misrepresent the results.

The record also illustrates why uncertainty and analysis details matter. Without an interval estimate, inferential analysis, or reported missing-data approach, readers cannot assess the statistical precision of the endpoint or evaluate the consequences of incomplete follow-up. The enrollment count is useful context, but it does not replace a reported analysis plan or a comparator group.

Finally, the registry distinguishes what the study set out to assess from what it reports as an outcome. The study description mentions safety and efficacy, but the listed outcome is serious adverse events and no efficacy result is reported. Keeping that distinction clear prevents a safety summary from being read as an efficacy conclusion. These are broadly useful principles for interpreting clinical-trial registry records, particularly when a study is single-arm and its posted results are descriptive.

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 main design limitation for interpretation is the absence of a concurrent comparator. With one open-label treatment group, the registry can describe events in the participants who received the regimen but cannot estimate how those events compare with another treatment or with no retreatment. The design also cannot by itself distinguish treatment-related events from events associated with systemic lupus erythematosus, other care, or chance.

The population was limited to participants previously enrolled in Genentech Study U2971g, and the registry describes moderate to severe systemic lupus erythematosus. The result therefore applies descriptively to this extension population; the record does not establish how well it generalizes beyond that group. The enrollment was 31, and no confidence interval is reported, leaving the precision of the serious-event estimate unquantified in the registry.

Important analysis details are not reported in the registry record. These include the analysis-population definition, missing-data handling, the number of participants with complete follow-up, and any statistical plan for efficacy reassessment. The registry lists one outcome measure and no analyses. The reason for the terminated status and the death count are not reported. Although the study description mentions efficacy assessment, no efficacy result is listed.

The registry reports a scheduled dosing regimen and pre-infusion medicines, but does not report whether all participants completed the planned schedule or how treatment interruptions were handled. These limitations constrain interpretation of both exposure and outcomes. They do not negate the recorded safety counts, but they mean those counts should remain descriptive and should not be extended into unsupported causal, comparative, or efficacy claims.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety of Rituximab Retreatment in Subjects With Systemic Lupus Erythematosus — NCT00381810.
• Registry record last updated 2017-08-01; status last verified 2017-06.
• Results first posted 2009-12-18.
• 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

NCT00381810 is a Phase II/III, open-label, single-arm, multicenter extension study of rituximab retreatment in participants with moderate to severe systemic lupus erythematosus who had previously enrolled in Protocol U2971g. The registry reports enrollment of 31 participants and a terminated status. Study dates recorded are 2006-06-22 for the start and 2008-07-31 for primary completion.

The regimen involved rituximab 1000 mg intravenously twice, 14 days apart at study entry and again 6 months later, with specified pre-infusion medicines. The primary outcome was the percentage of participants with at least one serious adverse event through up to 52 weeks. The safety record reports 11 affected participants among 31 at risk. No comparator, inferential analysis, efficacy result, death count, or reason for termination is reported in the registry record.