Sequential Natalizumab - Alemtuzumab Therapy in Patients With Relapsing Forms of Multiple Sclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sequential Natalizumab - Alemtuzumab Therapy in Patients With Relapsing Forms of Multiple Sclerosis (NCT03135249), a na phase 4 study. The primary outcome is Annualized Relapse Rate (ARR) From the Time of Cessation of Natalizumab Treatment..

2. Clinical Question

These details describe the question the study set out to address, not a conclusion about treatment effects. A single-group result can describe the recorded relapse experience after the treatment sequence, but by itself it cannot separate treatment effects from other explanations for what happened during follow-up. For example, without a concurrent comparison group, the registry record cannot show how the same participants would have fared under a different treatment strategy. The enrollment recorded is 9, but the number included in the primary outcome analysis is not reported in the registry record. Eligibility criteria, participant characteristics at baseline, and the way follow-up was handled are also not reported in the registry record.

3. Trial Design

This is a phase 4, single-group clinical study listed as completed. The registry identifies alemtuzumab as the intervention and describes a sequence in which participants with relapsing-remitting multiple sclerosis had previously received natalizumab. Allocation is recorded as not applicable, and masking is listed as none. These features mean that the registry does not describe random assignment to competing treatment groups or masking of participants or study personnel.

The recorded enrollment is 9. The study start date is 2018-05-01, and the primary completion date is 2020-11-04. The registry lists the University of Texas Southwestern Medical Center as sponsor. The title identifies the study as SUPPRESS, and the official title describes sequential natalizumab–alemtuzumab therapy in relapsing forms of multiple sclerosis.

The primary outcome is annualized relapse rate from the time of natalizumab cessation, with a stated timeframe of 12 months. The outcome description defines relapse rate using confirmed relapses and participant-years in study. The record also lists new T2 lesions, enlarging T2 lesions, and gadolinium-enhancing lesions among the secondary outcomes. It records 7 outcome measures, but the primary outcome result and results for the secondary outcomes are not reported in the registry record.

A study’s phase, completion status, and enrollment describe its registry design and administrative progress; they do not establish whether the treatment sequence changed an outcome. Because the design is single group, the study can be read as a description of outcomes among those treated, subject to the completeness of outcome ascertainment and analysis. A control-group estimate, randomized treatment contrast, and masking procedures are not reported in the registry record. The protocol details, analysis population, and statistical analysis plan are also 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.

Overall Study

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 Annualized Relapse Rate (ARR) From the Time of Cessation of Natalizumab Treatment., measured over 12 months.

The primary endpoint is annualized relapse rate from the time of natalizumab cessation. The registry defines this as the total number of confirmed relapses in the treatment group divided by the total participant-years of time in study. Its stated unit is number of relapses in a year, and the timeframe is 12 months. The listed summary is a mean with a 95% confidence interval.

In general, an annualized rate expresses events relative to time under observation. This can be useful when participants contribute different amounts of follow-up, because the rate’s denominator reflects person-time rather than treating all observation periods as identical. It remains important to know how relapses were confirmed, how follow-up time was defined, and how incomplete follow-up was handled. Those operational details are not reported in the registry record.

The endpoint is relevant to the study’s stated aim of assessing relapse rate after the treatment sequence. The study description also refers to a disease-free state over a 24 months period, while the primary outcome timeframe is 12 months. These are distinct statements in the record: the stated disease-free goal does not replace the specified primary endpoint or extend its listed timeframe. The observed rate, number of confirmed relapses, participant-years, and confidence interval are not reported in the registry record. Without those results, the magnitude and precision of the primary endpoint cannot be assessed from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as a mean for a continuous outcome and describes its dispersion using a 95% confidence interval. The outcome itself is an event rate: confirmed relapses relative to participant-years. These descriptions refer to different aspects of analysis. The rate defines the clinical quantity, while the mean and confidence interval indicate the planned summary and expression of uncertainty. The estimate and interval are not reported in the registry record.

What does annualized relapse rate represent?

In general, a rate relates the count of events to time at risk or time under observation. Expressing relapses per participant-year allows the denominator to reflect how much follow-up participants contribute. This is different from simply reporting the proportion of participants who experienced at least one relapse: a rate can include repeated events and incorporates observed time. The registry’s definition specifies total confirmed relapses divided by total participant-years in study. It does not report the component counts, the participant-time, or the resulting rate.

Rates require clear definitions of both events and time. In general, researchers must specify how events are confirmed, how recurrent events are counted, when follow-up begins and ends, and how periods without observation are treated. Those details affect the numerator and denominator. The registry states that the primary outcome begins at natalizumab cessation and has a 12 months timeframe, but the operational rules for censoring, interruptions, or incomplete follow-up are not reported in the registry record.

How should a confidence interval be read?

In general, a confidence interval describes the statistical uncertainty around an estimated quantity under a specified model and analysis procedure. It is not a guarantee that the true value lies within the interval, and its width does not capture every source of uncertainty. It does not account automatically for limitations such as selection, outcome measurement, or the absence of a control group. The registry lists a 95% confidence interval for the primary outcome, but neither the estimate nor the interval limits are reported in the registry record. Consequently, readers cannot use the posted information to assess the precision of the relapse-rate estimate.

For rate data, analysts may need to consider whether the variability is compatible with a simple count model. In general, over-dispersion occurs when event counts vary more than a model assumes; ignoring it can make uncertainty estimates too small. Recurrent events, differing observation time, and clustering can also matter to the analysis. This is general statistical context, not a description of the method used in this study. The model, variance method, and handling of repeated relapses are not reported in the registry record.

What does the single-group design allow?

The model is listed as single group, allocation as not applicable, and masking as none. In general, a single-group study can estimate or describe outcomes within the treated group, depending on the data and analysis. It does not create a randomized comparison with another strategy. Therefore, a within-group outcome cannot alone distinguish a treatment-related change from the natural course of disease, changes over time, selection into treatment, or other influences. The registry record does not report a control group or an adjusted comparison.

The record lists enrollment of 9, but does not state how many participants contributed to the primary outcome analysis. Enrollment and analysis population are not interchangeable: in general, participants may have missing outcome data, may not meet analysis criteria, or may contribute different observation time. The reasons for any exclusions, the analysis population definition, and the handling of missing information are not reported in the registry record. No conclusion about those features should be inferred from the enrollment figure alone.

What do the planning assumptions describe?

The planning illustration is described as using the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Its stated effect is a fraction of the observed effect. These are planning assumptions, not a description of the single-group trial’s observed outcomes or an analysis result. The listed illustration is not observed power. Sample-size illustrations are planning tools: they describe hypothetical design requirements under stated assumptions, rather than proving that a completed study had a particular probability of detecting an effect.

The planning description refers to two arms, whereas the trial itself is listed as single group and does not have a like-for-like control comparison. The planning assumptions therefore should not be mistaken for the trial’s allocation or observed design. The actual illustration values and the detailed statistical plan are not reported in the registry record. The record also does not report a sample-size justification for the completed trial, interim analyses, or a prespecified approach to the primary analysis. No inference about those elements can be made from the planning description alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and names annualized relapse rate as the primary outcome. It also identifies new T2 lesions, enlarging T2 lesions, and gadolinium-enhancing lesions as secondary outcomes. There are 0 analyses listed. Outcome listings identify what was to be measured, but do not explain how results were analyzed or how interpretation across multiple outcomes was managed.

In general, when a study evaluates multiple outcomes or performs multiple statistical tests, the chance of at least one apparently notable result can increase. A prespecified multiplicity strategy may define which outcome is primary, whether secondary outcomes are confirmatory or exploratory, and whether adjustments or a testing hierarchy are used. The multiplicity procedure, if any, is not reported in the registry record. The existence of several listed outcomes alone does not show that any particular adjustment was required or performed.

Missing-data methods and analysis populations are also not described. In general, incomplete follow-up can affect both the count of relapses and the participant-time used to calculate a rate. The impact depends on why observations are missing and how the analysis handles them. The registry does not report the number of participants contributing to the primary analysis, the amount or pattern of missing outcome data, imputation methods, censoring rules, or sensitivity analyses. These details are not reported in the registry record.

The record does not specify whether the analysis followed an intention-to-treat principle, used a per-protocol population, or applied another population definition. Nor does it report a protocol-level statistical analysis plan or interim-analysis procedures. These omissions limit assessment of how analysis choices may affect the posted results; because primary and secondary results are also not reported, the effects of any such choices cannot be evaluated from the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry records 0 serious adverse events among 9 participants at risk in the alemtuzumab treatment group. It records 0 other adverse events among 9 at risk and 0 deaths. No serious adverse event terms are listed. These are the safety counts recorded for the group, not a substitute for detailed event descriptions, timing, severity categories, or participant-level follow-up information.

In general, a count of zero means that no events of the specified category were recorded in the stated group under the registry’s reporting framework. It does not establish that an event is impossible, nor does it by itself show that the treatment is safe. Interpretation depends on the extent of monitoring, the definitions used, follow-up duration, completeness of reporting, and the amount of exposure. The record does not report these details sufficiently to assess them.

The safety figures should also be read in light of the single-group design. Without a concurrent comparison group, the counts do not estimate a comparative safety difference. The registry lists enrollment of 9, but the safety entries separately identify 9 participants at risk; the number of participants included in efficacy analyses is not reported in the registry record. No additional safety rate or percentage is calculated from these entries.

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

The registry record establishes that a phase 4, single-group study examined alemtuzumab after prior natalizumab treatment in people with relapsing-remitting multiple sclerosis. It identifies annualized relapse rate after natalizumab cessation as the primary outcome, with a 12 months timeframe, and lists brain lesion outcomes as secondary measures. It also records safety counts for the alemtuzumab group.

It does not report the primary relapse-rate estimate, its 95% confidence interval, or the results for the secondary outcomes. As a result, the posted information cannot establish the size or precision of the observed relapse rate. It also cannot show whether the treatment sequence changed relapse rate, induced peripheral tolerance, or established a disease-free state. Those aims appear in the study description, but an aim is not a result.

Even if an outcome estimate were available, a single-group design would not by itself establish what would have happened under another treatment strategy. In general, causal interpretation requires a comparison that supports inference about the counterfactual outcome. The registry does not list a concurrent control group or randomized allocation. Therefore, the design information does not support a like-for-like estimate of benefit or harm relative to another option.

The safety entries report 0 serious adverse events, 0 other adverse events, and 0 deaths, with 9 participants at risk for each adverse-event category. These counts are descriptive. They do not establish the absence of all possible harms, and the registry does not provide enough detail about monitoring or follow-up to assess the completeness of safety ascertainment.

In general, a registry record is useful for identifying a study’s stated question, design, endpoints, and reported results. Here, the primary and secondary outcome results and key analysis details are not reported in the registry record. The appropriate interpretation is therefore limited to the design and recorded safety information, without a conclusion about treatment effectiveness or comparative safety.

13. Why This Trial Matters Statistically

This study is statistically notable for the gap between its clinical question and the evidence a single-group design can provide. The study description asks whether a treatment sequence reduces annualized relapse rate and induces peripheral tolerance. Yet the registry lists no comparator, and the primary outcome result is not reported in the registry record. The design and available record therefore do not permit a treatment-effect estimate to be interpreted against a concurrent alternative.

The endpoint definition also highlights why time belongs in the analysis. Annualized relapse rate is defined using confirmed relapses and participant-years, so the estimate depends on both event ascertainment and follow-up time. In general, clear reporting of those elements, alongside an uncertainty interval, helps readers judge how informative a rate is. The registry specifies the intended summary and confidence interval but does not report the resulting estimate, interval, or component data.

The record also names several secondary imaging outcomes and indicates 7 outcome measures overall. In general, multiple outcomes make prespecification and transparent reporting important: readers need to know which results were primary, how other outcomes were treated, and whether multiplicity was addressed. The record identifies a primary outcome but does not report analyses or a multiplicity approach. Thus, it is not possible to assess the relationship between the outcome plan and the analyses performed.

Finally, the safety counts illustrate the limits of interpreting small descriptive records without fuller context. Counts of zero are useful to report, but they do not replace information about exposure, observation, and event definitions, or a comparison group for comparative safety inference. The registry entry is informative about what the study intended to evaluate and how it was classified; it is not sufficient to quantify the primary outcome or establish a comparative treatment effect.

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 most consequential limitation for interpretation is that the registry does not report the primary outcome estimate or its 95% confidence interval. Without these, the central outcome cannot be described quantitatively or assessed for precision. Results for the listed secondary outcomes are also not reported in the registry record, and there are 0 analyses listed.

The design is single group, with allocation recorded as not applicable and masking listed as none. There is no recorded concurrent comparison, so the study design does not provide a randomized, like-for-like contrast. This limits causal interpretation even if within-group outcome data are available elsewhere. A treatment effect relative to another strategy is not reported in the registry record.

Enrollment is recorded as 9, but the number included in the primary analysis is not reported in the registry record. The record does not describe baseline participant characteristics, eligibility criteria, attrition, follow-up completeness, missing-data handling, relapse confirmation procedures, or analysis populations. These are specific uncertainties because the endpoint relies on confirmed events and participant-time.

The statistical methods are incompletely documented. The registry specifies a mean and 95% confidence interval for the primary outcome, but does not report the model, variance approach, analysis plan, multiplicity strategy, or interim-analysis procedures. Although a planning illustration is described, its assumptions do not establish the completed study’s actual sample-size justification or analysis method.

The safety entries report zero recorded events in the listed categories, but detailed safety definitions, monitoring, and follow-up are not reported in the registry record. The available information is therefore insufficient to assess the completeness of event ascertainment or compare safety with another treatment. The stated goal of a disease-free state over a 24 months period should also be distinguished from the primary outcome’s specified 12 months timeframe.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sequential Natalizumab - Alemtuzumab Therapy in Patients With Relapsing Forms of Multiple Sclerosis — NCT03135249.
• Registry record last updated 2022-02-15; status last verified 2022-01.
• Results first posted 2022-02-15.
• 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

The registry record describes SUPPRESS, a phase 4, completed, single-group study sponsored by the University of Texas Southwestern Medical Center. Enrollment is 9; the recorded start date is 2018-05-01, and the primary completion date is 2020-11-04. The population is described as people with relapsing-remitting multiple sclerosis previously treated with natalizumab, followed by alemtuzumab.

The primary outcome is annualized relapse rate after natalizumab cessation over 12 months, defined using confirmed relapses and participant-years. Listed secondary outcomes include new T2 lesions, enlarging T2 lesions, and gadolinium-enhancing lesions. The primary estimate, confidence interval, secondary results, and analysis population are not reported in the registry record.

The safety entries record 0 serious adverse events, 0 other adverse events, and 0 deaths in the alemtuzumab group. The design has no recorded comparator; allocation is not applicable and masking is none. These registry entries describe the registry entry but do not establish a treatment effect or comparative safety conclusion.