Study to Assess Safety and Effectiveness of Branebrutinib Treatment in Participants With Active Systemic Lupus Erythematosus or Primary Sjögren's Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Study Participants With Active Rheumatoid Arthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Safety and Effectiveness of Branebrutinib Treatment in Participants With Active Systemic Lupus Erythematosus or Primary Sjögren's Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Study Participants With Active Rheumatoid Arthritis (NCT04186871), a randomized phase 2 study. The primary outcome is The Percent of Participants With mCLASI Response at Week 24 and Corticosteroid (CS) < 10 mg/Day at Week 20 and Week 24 - SLE.

2. Clinical Question

The study also included participants with primary Sjögren’s Syndrome (pSS) and rheumatoid arthritis (RA), but the posted primary endpoint pertains only to SLE. The broader study evaluated branebrutinib in SLE and pSS, and branebrutinib followed by open-label abatacept in RA. Those distinct cohorts and treatment sequences should not be conflated with the SLE placebo-controlled primary comparison. The central statistical question is about the frequency of a defined combined response, not about change in mCLASI alone or about outcomes in the other cohorts.

3. Trial Design

This was a Phase 2, randomized, placebo-controlled, double-blind, multicenter study with a parallel design and quadruple masking, according to the registry record. The study enrolled 119 participants overall. It included SLE, pSS, and RA cohorts. The SLE and pSS cohorts had branebrutinib and placebo groups. In the RA cohort, the treatment strategies were branebrutinib followed by open-label abatacept and placebo followed by abatacept. The primary endpoint was specified for the SLE cohort only.

The registry lists the study as starting on 2020-01-07, with primary completion on 2022-12-05, and status as completed. The sponsor is Bristol-Myers Squibb. These details describe the registered study structure and timeline; they do not establish how participants were distributed across every cohort or how many participants completed each assessment. The overall enrollment of 119 should not be read as the sample size for the SLE primary comparison. The posted primary endpoint counts are 5 for SLE placebo and 15 for SLE branebrutinib.

The record identifies drug interventions but leaves the arm descriptions empty. Dose, treatment duration, allocation ratio, stratification factors, and the operational details of masking are not reported in the registry record. Although the official title describes the study as randomized, placebo-controlled, double-blind, and multicenter, the registry’s masking field says quadruple. These labels do not by themselves explain which parties were masked or how masking was maintained. Further details about random sequence generation, allocation concealment, and departures from assigned treatment are not reported in the registry record.

Separate disease cohorts and treatment strategies mean that an overall enrollment figure cannot be used to infer the precision of any one cohort’s estimates. The primary comparison is especially limited by the small posted SLE endpoint denominators. Results from RA or pSS do not directly answer the SLE primary question, and the open-label abatacept stage in the RA strategy differs from the placebo-controlled SLE comparison.

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: Participants were enrolled concurrently for the RA, SLE, and pSS sub-studies.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All treated participants with a baseline mCLASI activity score ≥ 10 at Week 24 (Prespecified for participants in the SLE cohort only).

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as The Percent of Participants With mCLASI Response at Week 24 and Corticosteroid (CS) < 10 mg/Day at Week 20 and Week 24 - SLE, measured over Week 24.

The primary endpoint is the percentage of participants meeting a combined response definition at Week 24 in the SLE cohort. Participants needed a baseline mCLASI activity score ≥ 10. The mCLASI response component required a decrease of ≥ 50% from baseline by Week 24. The registry describes mCLASI as a modified measure of cutaneous lupus disease activity based on skin erythema, scale or hypertrophy, and scalp inflammation. Its score is calculated by simple addition based on symptom extent.

The endpoint combines this skin response criterion with a corticosteroid criterion. The title refers to CS < 10 mg/day at Week 20 and Week 24. The description states that the prednisone or equivalent dose had to remain stable and ≤ 10 mg from Week 16 until Week 24. The registry therefore gives both a title and a more detailed description; the distinction between < 10 mg in the title and ≤ 10 mg in the description should be noted rather than silently resolved. Baseline values are defined as the last nonmissing value before the first dose of study treatment.

General statistical context: a combined endpoint can represent success only when all specified components are met, so it captures a more constrained response than the skin measure alone. It can be useful when the clinical question includes both improvement in disease activity and a treatment-related condition such as corticosteroid stability. The registry states that a ≥ 50% mCLASI decrease in participants starting with a score ≥ 10 is considered likely to represent clinically meaningful improvement. This endpoint is not a direct measure of every aspect of SLE activity, and it should not be interpreted as the primary result for pSS or RA.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each eligible participant either meets the combined response definition or does not. The registry reports percentages for the SLE placebo and branebrutinib groups, together with a response difference and an odds ratio. The posted group counts are 5 for placebo and 15 for branebrutinib. These are the endpoint denominators and should not be confused with the total study enrollment of 119.

What does the confidence interval communicate?

General statistical explanation: a confidence interval expresses the uncertainty associated with an estimate under a specified statistical procedure and its assumptions. A narrow interval indicates greater precision; a wide interval indicates less precision. For the reported response difference, the 95% confidence interval is -77.5 to 21.9. For the odds ratio, it is 0.04 to 2.73. Both intervals cover values that point in different directions or toward different degrees of association. The estimates are therefore imprecise. The registry does not report further detail about the confidence-interval calculation for the response difference.

The odds ratio was analyzed using the Cochran-Mantel-Haenszel method. General statistical explanation: this method can estimate an association between treatment group and a binary outcome while accounting for defined strata. The registry record does not identify any strata or describe the specific implementation, so the role of stratification in this analysis cannot be assessed. The reported odds ratio is 0.32, with a 95% confidence interval of 0.04 to 2.73 and p = 0.312. The confidence interval and p-value are part of the registry’s reported analysis; the p-value is not a measure of the probability that a treatment effect is true.

How should the recalculated RA comparisons be read?

The recalculated RA contrasts use posted group means and standard deviations to form simple, unadjusted comparisons. For DAS28-CRP, the mean difference is 0.073 with a 95% interval from -0.532 to 0.678 and an unadjusted p-value of 0.813. For DAS28-ESR, the mean difference is 0.088 with a 95% interval from -0.513 to 0.689 and an unadjusted p-value of 0.774. For SDAI, the mean difference is 1.127 with a 95% interval from -5.27 to 7.524 and an unadjusted p-value of 0.73. These estimates compare branebrutinib with placebo using the posted change-from-baseline summaries; they are not adjusted analyses.

General statistical explanation: an unadjusted comparison does not account for covariates or other design features beyond the information built into the calculation. It can be useful as a transparent summary of posted means and variability, but it may not reproduce a trial’s prespecified analysis. The registry’s reported RA analyses are group-specific mean differences in final values, not the same pairwise change-from-baseline contrasts. Thus the recalculated comparisons and the reported within-group analyses address different statistical quantities.

The registry reports standard deviations for the RA outcomes. General statistical explanation: a standard deviation describes variation among participant measurements, while a standard error describes uncertainty in an estimated mean. Larger variability and smaller group sizes generally make estimates less precise. The posted RA group sizes vary by outcome, and are much smaller than the overall enrollment; they determine the precision of these particular comparisons.

What do the planning illustrations represent?

The sample-size illustrations use the observed effect as a planning input and assume a two-sided significance level of 0.05, equal allocation, and a normal approximation. For each outcome, they present participant counts per arm for 80% and 90% power at 100%, 75%, and 50% of the observed effect. For example, the DAS28-CRP illustration gives 3,617 participants per arm for 80% power at 100% of the observed effect, and 6,430 participants per arm for 80% power at 75% of that effect. These are planning illustrations, not evidence about the trial’s achieved power, actual design requirements, or observed enrollment targets. The trial’s own sample-size justification is not reported in the registry record.

General statistical explanation: planning calculations depend on assumptions about the effect to detect, variability, allocation, significance level, and statistical model. Using an effect estimated from a small study can produce unstable projections, particularly when the estimate is near zero. The illustrations should therefore be treated as conditional scenarios, not as forecasts. Over-dispersion is most directly relevant to count data when variability exceeds a model’s assumed level; the endpoints are binary percentages or continuous scores, and a specific over-dispersion analysis is not reported in the registry record.

The record does not report the full statistical analysis plan, interim analyses, covariate adjustment details, or handling of missing outcomes. Those omissions limit independent assessment of whether the posted analyses follow a prespecified plan. The stated analysis population for the primary endpoint is all treated participants with baseline mCLASI activity score ≥ 10, but additional operational definitions and missing-data procedures 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("SLE- Placebo", "SLE- Branebrutinib")
n      <- c(5, 15)
events <- c(3, 5)
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  SLE- Placebo  5  3  60.0  14.7  94.7  23.1  88.2  22.3  88.2
ARM  SLE- Branebrutinib  15  5  33.3  11.8  61.6  15.2  58.3  15.2  58.7

11. Analyses Reported by the Sponsor

The sponsor’s posted primary analysis is the Cochran-Mantel-Haenszel odds ratio: 0.32, with a 95% confidence interval from 0.04 to 2.73 and p = 0.312. The registry also reports a response difference of -27.8, with a 95% confidence interval from -77.5 to 21.9. These are the sponsor’s reported primary comparison results. No discrepancy is flagged between a sponsor result and a recalculation for this primary binary endpoint.

The recalculated comparisons described for the RA outcomes are simple unadjusted comparisons based on posted group means and standard deviations. They are not substitutes for a sponsor analysis. The registry’s reported analyses for those RA measures give separate mean differences in final values within each group; they do not report the same pairwise, change-from-baseline contrasts as the recalculations. The two types of result answer different questions, so agreement or disagreement should not be inferred by treating them as identical estimates.

For the primary endpoint, the registry’s sponsor analysis should be the principal reported inferential result. Its interval is broad, and its p-value does not establish a group difference. The recalculated RA results are supplementary descriptive comparisons, not an alternative sponsor analysis or a basis for overriding the registry’s reported primary result. Further details about the sponsor’s full analysis plan, including any covariate adjustment or missing-data procedures, are not reported in the registry record.

12. Multiplicity, Missing Data and Analysis Populations

The registry record lists 11 outcome measures and 27 analyses, as well as 8 posted secondary outcomes. It does not report whether the primary and secondary hypotheses were organized into a prespecified testing hierarchy, whether p-values were adjusted for multiplicity, or whether any outcomes were designated exploratory. Without those details, the interpretation of multiple tests cannot be fully assessed. General statistical context: when many outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase. A multiplicity strategy may control that risk, but no such strategy is reported in the registry record.

Missing-data handling is also not reported in the registry record. The primary endpoint is described for all treated participants with baseline mCLASI activity score ≥ 10, but the record does not specify how missing Week 24 assessments, missing corticosteroid data, or treatment discontinuations were handled. It does not report imputation methods, sensitivity analyses, or the number of eligible participants lacking endpoint data. The small posted endpoint denominators—5 for placebo and 15 for branebrutinib—make clear that only a limited number of participants contribute to the reported percentages, but the reason for those denominators is not reported in the registry record.

The record does identify the primary endpoint population as treated participants meeting the baseline mCLASI criterion. It does not report further detail about whether the analysis followed an intention-to-treat, per-protocol, or other population definition, nor does it explain how participants were classified if treatment or assessment procedures changed. The primary endpoint title and description also differ in the corticosteroid threshold wording: the title says < 10 mg/day at Week 20 and Week 24, while the description specifies a stable dose ≤ 10 mg from Week 16 to Week 24. The registry record does not explain this difference.

Interim analyses and stopping rules are not reported in the registry record. The sample-size justification and any assumptions used for the original design are also not reported in the registry record. These gaps do not alter the posted results, but they limit assessment of how analysis choices, missing information, and multiple testing may affect interpretation.

13. 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 non-serious adverse event terms

For the SLE groups, the registry reports 0 serious adverse events among 5 placebo participants at risk and 0 among 15 branebrutinib participants at risk. It reports 0 deaths in each of these groups. For other adverse events, 4 of 5 placebo participants and 14 of 15 branebrutinib participants were affected. These are counts of participants affected, not counts of individual event episodes.

Across the pSS groups, serious adverse events and deaths are reported as 0 in both groups; other adverse events affected 4 of 4 placebo participants and 8 of 10 branebrutinib participants. In RA, serious adverse events and deaths are reported as 0 in the placebo, branebrutinib, and abatacept groups. Other adverse events affected 6 of 21 participants in the RA placebo group, 13 of 64 in the RA branebrutinib group, and 5 of 81 in the RA abatacept group. These groups correspond to the registry’s safety categories and should not be taken as direct randomized comparisons across all treatment stages.

General statistical context: zero observed serious events in a group does not show that the underlying risk is zero, particularly when the group is small. The registry does not report the safety observation period, event definitions beyond the serious-versus-other categories, or detailed event terms in the posted safety results. The counts therefore describe reported participant incidence, but do not by themselves establish comparative safety or characterize event severity and timing.

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

The primary result describes the observed percentage of eligible treated SLE participants who met the registry’s combined skin-response and corticosteroid criterion at Week 24. The placebo percentage was 60.0% among 5 participants, and the branebrutinib percentage was 33.3% among 15 participants. The reported response difference and odds ratio both have broad confidence intervals. The data therefore offer an uncertain estimate of the group contrast rather than a precise answer.

The result does not isolate the mCLASI component from the corticosteroid condition. It does not show how many participants met each component separately, and it does not provide an estimate for people outside the defined SLE population. The result is not a primary assessment of pSS or RA, and the three available RA secondary comparisons cannot be substituted for the SLE endpoint.

General statistical context: an estimate is not the same as a definitive conclusion. A confidence interval expresses uncertainty under the analysis assumptions, while a p-value measures how unusual data at least as inconsistent with a specified null model would be if that model held. Neither quantity provides the probability that a treatment is effective or ineffective. Here, the primary interval includes a wide range of possible contrasts, and the reported p-value is 0.312. The posted results do not establish a clear between-group difference.

The result also does not establish that there is no difference. A small endpoint sample can leave substantial uncertainty even when the observed percentages differ. Nor can the sample-size illustrations be read as observed power or evidence of what the study was designed to detect: they are planning scenarios based on the observed effects and stated assumptions. Missing-data methods, the original sample-size rationale, and the full statistical plan are not reported in the registry record.

Accordingly, the most defensible reading is limited: the registry reports a low-precision primary comparison in a small SLE endpoint population, with no clear inferential evidence of a difference in the posted analysis. The wider study includes other diseases and treatment strategies, but those results do not resolve the uncertainty around this particular primary endpoint.

15. Why This Trial Matters Statistically

This trial illustrates why an overall enrollment figure is not enough to judge the precision of a particular result. Although 119 participants were enrolled across the study, the primary endpoint applies only to treated SLE participants meeting a baseline mCLASI threshold, and the posted comparison includes 5 placebo participants and 15 branebrutinib participants. The uncertainty of the primary estimate is shaped by this endpoint-specific population, not by the total enrollment alone.

It also illustrates how endpoint definitions affect interpretation. The primary outcome combines a skin response with a corticosteroid condition, so its percentage represents a joint criterion. The registry’s wording differs between the endpoint title and its detailed definition on the corticosteroid threshold. That distinction matters for reproducibility and for understanding exactly which participants count as responders.

General statistical context: sparse binary data often produce wide uncertainty intervals, particularly when one group has few observations. Reporting an effect estimate alongside its confidence interval makes this uncertainty visible. The primary response difference and odds ratio convey the comparison on different scales, while the small denominators and broad intervals caution against strong claims based on the point estimates alone.

The trial also shows why primary and secondary findings need separate interpretation. The available RA mean-change comparisons are unadjusted and concern a different cohort and outcomes. The registry does not report how multiplicity was handled across the listed outcomes. Without that information, secondary results should not be treated as equivalent to prespecified primary evidence or as confirmation of the SLE result.

Finally, the record offers a useful distinction between sponsor-reported analyses and simple recalculations from summary statistics. They can differ in estimand and method. The registry’s reported primary analysis remains the principal inferential result, while recalculated secondary comparisons provide limited, transparent context rather than a replacement analysis.

16. 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.

Several trial-specific limitations constrain interpretation. First, the SLE primary endpoint has a small posted comparison population: 5 participants in the placebo group and 15 in the branebrutinib group. The resulting confidence intervals are wide, so the response difference and odds ratio are imprecise. The registry does not explain why these endpoint denominators are smaller than overall enrollment or provide a flow of participants through screening, treatment, and assessment.

Second, the primary endpoint is a combined criterion. The record does not report component-level counts for mCLASI response and corticosteroid status, so it is not possible to identify which component most often determined whether the combined endpoint was met. The title specifies CS < 10 mg/day at Week 20 and Week 24, while the endpoint description specifies a stable dose ≤ 10 mg from Week 16 to Week 24. The registry record does not explain the difference in wording.

Third, the record does not report the analysis plan in enough detail to assess stratification, adjustment, missing-data handling, sensitivity analyses, or the full definition of the primary analysis population. It also does not report the study’s sample-size justification, interim analyses, or a multiplicity strategy. The absence of these details limits independent evaluation of design assumptions and inferential procedures.

Finally, detailed numerical results are available for only three RA secondary outcomes in the material described by the record, despite the listing of 8 secondary outcomes. These are recalculated unadjusted comparisons and do not reproduce the registry’s reported group-specific final-value analyses. They are not direct evidence about the SLE primary endpoint. Safety counts are reported without an observation period or detailed event-term breakdown, which limits assessment of timing and event characteristics.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Study to Assess Safety and Effectiveness of Branebrutinib Treatment in Participants With Active Systemic Lupus Erythematosus or Primary Sjögren's Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Study Participants With Active Rheumatoid Arthritis — NCT04186871.
• Registry record last updated 2024-01-16; status last verified 2024-01.
• Results first posted 2024-01-16.
• 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.

20. Record Summary

NCT04186871 is a completed Phase 2 randomized, placebo-controlled, double-blind, multicenter, parallel study with quadruple masking. Overall enrollment was 119. The study involved SLE and pSS branebrutinib-versus-placebo cohorts and an RA strategy of branebrutinib followed by open-label abatacept or placebo followed by abatacept. The registry lists a start date of 2020-01-07 and primary completion on 2022-12-05.

The primary endpoint was the Week 24 percentage meeting a combined mCLASI response and corticosteroid criterion in treated SLE participants with baseline mCLASI activity score ≥ 10. The posted percentages were 60.0% for placebo and 33.3% for branebrutinib, with a response difference of -27.8 and 95% confidence interval from -77.5 to 21.9. The reported odds ratio was 0.32, with 95% confidence interval from 0.04 to 2.73 and p = 0.312. The small endpoint groups and broad intervals indicate substantial uncertainty. Important details about missing data, multiplicity, and the full analysis plan are not reported in the registry record.