Ustekinumab for the Treatment of Giant Cell Arteritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ustekinumab for the Treatment of Giant Cell Arteritis (NCT02955147), a na phase 1, phase 2 study. The primary outcome is Percentage of Patients in Glucocorticoid-free Remission.

2. Clinical Question

The study's stated purpose was to determine whether ustekinumab was effective in treating giant cell arteritis. Statistically, its primary question concerns the proportion of participants who satisfy a composite remission definition at a specified follow-up time. The endpoint is not simply symptom improvement or cessation of prednisone: all listed criteria must be met.

Because ustekinumab was combined with prednisone and the study had no control group, the result could not isolate the contribution of either drug from the other, the natural course of disease, or other influences. The record lists disease flare and cumulative prednisone dose as secondary outcomes, but does not report their results. It also does not report an analysis of the primary endpoint.

3. Trial Design

The record describes an open-label study in phase 1 and phase 2. Its design is single-group, with allocation recorded as not applicable and masking recorded as none. The only described treatment group received ustekinumab plus prednisone. There is no concurrent comparison group in the registry record, so this is not a randomized comparison of treatment strategies.

The ustekinumab schedule was 90 mg subcutaneously at baseline, week 4, week 12, week 20, week 28, week 36 and week 44. Prednisone was planned as a taper following predefined schedules, beginning at 60 mg, 40 mg or 20 mg. The available arm description ends partway through its account of the prednisone regimen, so further details of that regimen are not reported in the registry record.

The primary endpoint was assessed at 52 weeks. The record lists enrollment of 13 and identifies Massachusetts General Hospital as sponsor. The study status is terminated; the recorded start date is 2016-12-01 and the primary completion date is 2019-07-25. The reason for termination is not reported in the registry record, and the status alone does not establish why the study ended.

A single-group design can describe outcomes among participants receiving the study regimen, but it cannot estimate the contrast that a randomized control group would provide. Without that contrast, changes over time cannot be attributed uniquely to ustekinumab or to the combination regimen. The registry record does not report the rationale for selecting the design, the sample-size justification, or a sponsor-authored statistical analysis plan.

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: Three patients failed the screening due to dementia (N = 1), severe prednisone-induced depression (N = 1), and positive hepatitis B core antibody (N = 1)

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 Percentage of Patients in Glucocorticoid-free Remission, measured over 52 weeks.

The primary endpoint is the number of participants in glucocorticoid-free remission at 52 weeks. The registry defines prednisone-free remission using three requirements: absence of relapse from the time remission was achieved through week 52; normalization of ESR (<40 mm/hour) and CRP (<10 mg/L); and adherence to the protocol prednisone taper. A participant must meet all of these conditions for the composite endpoint.

This kind of endpoint is used to represent a clinically meaningful state across disease control, inflammatory markers and steroid exposure. It is more informative than a measure that considers only one of those dimensions, but the combined definition also means that failure to meet any one condition prevents classification as remission. Interpretation therefore depends on the exact definition and on consistent assessment of each component.

The endpoint is recorded as a participant count, rather than a continuous measurement. For a count endpoint, the numerator would be the participants meeting the definition and the relevant denominator would be the participants assessed. Neither the primary remission count nor its analysis denominator is reported in the registry record. Consequently, the primary result and its precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint, each participant is classified according to whether the defined event occurred. In this study, the primary event is meeting the full definition of prednisone-free remission at 52 weeks. A usual summary would report the number meeting the definition and the number assessed, with an estimate of the proportion and an interval describing uncertainty. The registry record reports the endpoint definition but not those results, so no such estimate can be interpreted.

What does a confidence interval convey?

In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. A narrow interval indicates greater precision than a wide interval, while neither interval alone resolves design limitations such as lack of a comparator. For a participant-count outcome, limited data can make the interval wide, especially when few participants meet the endpoint. No confidence interval for the primary outcome is reported in the registry record.

What can a single-group estimate answer?

In general, a single-group estimate describes an outcome frequency within the observed group under its care regimen. It does not directly estimate the difference between that regimen and an alternative. A randomized comparison helps distinguish treatment effects from other causes of outcome differences by assigning participants to comparison groups. This study is recorded as single-group, with allocation not applicable and no masking. Consequently, any outcome description would remain descriptive and could not separate the effects of ustekinumab, prednisone, their combination, or other influences.

How should planning calculations be read?

The registry record distinguishes planning illustrations from the trial's own design. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the target effect expressed as a stated fraction of an observed effect. These are hypothetical planning assumptions, not evidence that this study used two arms, randomized participants, or had a sponsor-specified power calculation. In fact, the recorded study design is single-group. The record does not report the trial's sample-size justification or a sponsor-authored statistical plan.

Sample-size planning asks how much information a future study might need to detect a target effect under chosen assumptions. It is not a measure of the probability that a completed study's finding is true, and it is not observed power. In a binary outcome, planning depends on assumptions about the event frequency, target contrast, significance level, allocation and analysis method. If those inputs are uncertain or do not match the eventual design, the planning result may not transfer. No numerical planning results or trial-specific target effect are reported in the registry record.

Why does over-dispersion matter?

In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. It can make standard errors too small if ignored, producing intervals that are too narrow and tests that appear more conclusive than the data warrant. It is most relevant to outcomes modeled as counts or rates when events vary more than the chosen distribution allows. The primary endpoint is recorded as a participant count with a binary meaning, not as a rate model, and the record does not report an over-dispersion analysis. No model-based estimates are listed.

For time-to-event outcomes, methods commonly account for the timing of events and for participants who have not yet experienced an event by the end of observation. The record lists disease flare as a secondary outcome, but does not report a time-to-event analysis, event times, censoring information or results. The general availability of such methods does not establish that they were used in this study.

Finally, an analysis requires a defined population, outcome data and rules for handling incomplete observations. The registry record lists enrollment but does not report the number included in each outcome analysis, missing-data procedures, or analysis-population definitions. With no listed analyses, statistical-method details beyond the design and endpoint definition are not reported in the registry record.

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("Ustekinumab Plus Prednisone")
n      <- c(13)
events <- c(3)
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  Ustekinumab Plus Prednisone  13  3  23.1  5.0  53.8  8.2  50.3  8.4  50.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes of disease flare and cumulative prednisone dose. It does not report a statistical analysis plan, a hierarchy for testing outcomes, an adjustment for multiple comparisons, or the number of planned hypotheses. Without that information, the handling of multiplicity is not reported in the registry record. In general, testing several outcomes can increase the chance of at least one apparently unusual result, so prespecified priorities and interpretation rules matter.

The record identifies 4 outcome measures, but does not provide analysis results for them. It reports 0 analyses. There is no reported primary endpoint count, secondary outcome result, confidence interval or p-value. The number assessed for each outcome and the reasons for any missing observations are not reported in the registry record.

Missing-data methods affect which participants contribute to an estimate and how incomplete follow-up is treated. In general, complete-case analysis uses participants with the relevant observed data, while other approaches make additional assumptions about missing outcomes. No such approach or analysis population is specified in the record. Therefore, the enrolled group should not automatically be treated as the denominator for every outcome, and the enrollment figure does not establish completeness of follow-up.

The registry record also does not report interim analyses, stopping rules, or whether outcome definitions or analysis methods changed. The terminated status is recorded, but the reason and any statistical decisions associated with termination are not reported in the registry record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diverticulitis (7.7%).

The adverse-event record lists the Ustekinumab Plus Prednisone group with 13 participants at risk for serious adverse events and 1 affected by a serious adverse event. For other adverse events, it lists 13 at risk and 4 affected. The record lists 0 deaths. It also identifies diverticulitis among the top serious terms, at 7.7%.

These are descriptive safety counts for the recorded group. They should not be read as a comparison with another treatment, because the study had no control group. The serious and other adverse-event categories are reported separately; the record does not explain whether participants could appear in both categories, nor does it provide event-level detail or a comparison of exposure time. The term listing does not establish that diverticulitis was caused by study treatment.

Safety counts also require context about observation duration, completeness of reporting and the definitions used to classify events. Those details are not fully reported in the registry record. With this group's recorded enrollment, the safety findings should be interpreted as limited observations, not as precise estimates of the frequency of uncommon events or as comparative safety evidence.

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

The record documents an open-label, single-group study of ustekinumab given with prednisone in patients with giant cell arteritis. It specifies a primary endpoint focused on prednisone-free remission at 52 weeks and defines remission using relapse status, inflammatory markers and adherence to the prednisone taper. These details clarify what the study intended to assess.

The record does not report the primary endpoint result or any analysis. It therefore does not establish how many participants achieved remission, how uncertain an estimated remission frequency would be, or whether the endpoint differed from an outcome under another treatment. The stated aim of determining whether ustekinumab is effective is a purpose, not a reported finding.

Even a reported remission frequency from this design would describe participants receiving the combination regimen rather than identify the effect of ustekinumab alone. Prednisone was part of the intervention, and there was no separate control group. A comparative conclusion would require an appropriate comparison and analysis, neither of which is reported.

The safety record offers counts of serious and other adverse events and lists diverticulitis as a serious term. These observations can describe what was recorded in the group, but cannot establish comparative risk or causal attribution. The record does not provide enough information to characterize rare harms or fully assess safety over time.

Accordingly, the registry record is informative about study design, treatment schedule, endpoint definition and some safety reporting. It does not provide the outcome analyses needed to support a conclusion about efficacy, comparative effectiveness or a complete benefit-risk assessment.

14. Why This Trial Matters Statistically

This study illustrates why a defined endpoint and a reported result are both necessary for statistical interpretation. The remission definition combines clinical course, inflammatory-marker thresholds and the prednisone taper. Each component contributes to the classification, so a result would need to be understood in light of the full composite definition rather than as a simple measure of symptom change or steroid use.

It also highlights the distinction between describing outcomes and estimating treatment effects. A single-group design can document what occurred among participants receiving a regimen. Without a control group, it cannot tell whether the same outcomes would have occurred under another approach. This distinction is especially important when an intervention is combined with another active treatment, as ustekinumab was combined with prednisone in this study.

Statistical precision is another concern. The registry records enrollment of 13, yet reports no primary endpoint count or interval. Without those results, readers cannot assess the estimated frequency or its uncertainty. Even when counts are available, limited data can leave substantial uncertainty; a point estimate alone would not convey that uncertainty.

Finally, the terminated status and absence of reported analyses raise questions that the record does not answer. The reason for termination, missing-data handling, analysis populations, and any analysis plan are not reported. Recognizing these gaps is not a judgment about the study's conduct; it is a boundary on what can be concluded from the registry record.

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 limitation for interpretation is that the registry record does not report the primary remission result or any outcome analysis. Without the numerator, analysis denominator and uncertainty estimate, the intended primary question cannot be answered from the record. Secondary outcomes are named, but their results are also not reported.

The single-group, open-label design has no concurrent control and cannot provide a randomized treatment contrast. Because ustekinumab was administered with prednisone, any observed outcome could reflect the combination, the prednisone course, other influences, or their interaction. The design cannot isolate the contribution of ustekinumab.

The record lists enrollment of 13, but does not report how many participants were assessed at 52 weeks or included in each analysis. It does not describe withdrawals, missing endpoint components, analysis-population rules or methods for handling incomplete data. The arm description also ends partway through the prednisone regimen, limiting detail about the taper schedules.

The status is terminated, but the reason is not reported in the registry record. Nor are the sample-size justification, interim analyses, stopping rules or sponsor-authored statistical plan reported. These absences prevent assessment of whether the study's size and analysis strategy were prespecified or how termination affected interpretation. Safety observations are likewise limited to the recorded group, without comparative data or full event-level context.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ustekinumab for the Treatment of Giant Cell Arteritis — NCT02955147.
• Registry record last updated 2020-06-12; status last verified 2020-06.
• Results first posted 2020-06-12.
• 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

NCT02955147 is an open-label phase 1 and phase 2, single-group study titled Ustekinumab for the Treatment of Giant Cell Arteritis. Massachusetts General Hospital is listed as sponsor. The study record lists enrollment of 13, status terminated, start date 2016-12-01 and primary completion date 2019-07-25.

The treatment group received ustekinumab plus prednisone. The primary outcome was the number of participants in prednisone-free remission at 52 weeks, with remission defined by absence of relapse after remission, normalized ESR and CRP, and adherence to the protocol taper. Disease flare and cumulative prednisone dose are listed as secondary outcomes.

The record reports no outcome analyses and does not report the primary endpoint result. It lists serious and other adverse-event counts, 0 deaths, and diverticulitis among the top serious terms at 7.7%. The reason for termination, analysis populations and missing-data procedures are not reported in the registry record.