A Study to Evaluate the Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil (MMF) in Participants With Pemphigus Vulgaris (PV): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil (MMF) in Participants With Pemphigus Vulgaris (PV) (NCT02383589), a randomized phase 3 study. The primary outcome is Percentage of Participants (Excluding Telemedicine [TM] Participants) Who Achieved Sustained Complete Remission, Evaluated by the Pemphigus Disease Area Index (PDAI) Activity Score.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, double-blind, double-dummy, active-comparator, parallel-arm, multicenter study of rituximab and mycophenolate mofetil in pemphigus vulgaris. The registry records an enrollment of 135. Its description says participants were randomized in a 1:1 ratio, with randomization stratified by duration of illness. The study was sponsored by Hoffmann-La Roche.

The treatment period was 52 weeks. A screening period of up to 28 days preceded treatment, followed by a 48-week safety follow-up period beginning at treatment completion or discontinuation. The study began on 2015-05-26, reached primary completion on 2018-11-28, and is recorded as completed. The brief description anticipated enrollment at up to 60 centers worldwide.

Participants assigned to rituximab received intravenous infusions on Days 1 and 15, with repeat administrations on Days 168 and 182 if specified safety criteria were met. They also took mycophenolate mofetil matching placebo twice daily through Week 52. The comparison group took mycophenolate mofetil twice daily through Week 52 and received matching rituximab placebo infusions on the planned days. This double-dummy arrangement used matching placebo treatments to help maintain masking across different routes of administration.

The registry reports 62 participants in the rituximab primary analysis group and 63 in the mycophenolate mofetil group. The primary analysis population was modified intent-to-treat: it included participants in the stated intent-to-treat population who received any part of an infusion or oral study drug, but excluded the 10 telemedicine participants. The registry record does not report the original sample-size justification or further details of the 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.

Treatment Period

Reasons for not completing this period:

Safety Follow-up (SFU)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The modified intent-to-treat (mITT) population included participants in the ITT population (all randomized participants who received any part of an infusion of study drug or oral administration of study drug), excluding the 10 telemedicine (TM) participants. This population was used in the analyses of efficacy outcomes.

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 (Excluding Telemedicine [TM] Participants) Who Achieved Sustained Complete Remission, Evaluated by the Pemphigus Disease Area Index (PDAI) Activity Score, measured over From Baseline up to 52 Weeks (up to clinical cut-off date (CCOD) of 28 November 2018).

The primary endpoint is the percentage of participants, excluding telemedicine participants, who achieved sustained complete remission as evaluated by the Pemphigus Disease Area Index (PDAI) activity score. The assessment covers baseline through 52 weeks, up to the clinical cut-off date of 28 November 2018. The registry describes the endpoint as a count-based parameter displayed as a percentage of participants.

Complete remission is a clinically interpretable state, while the word “sustained” indicates that the outcome is intended to capture remission maintained over time rather than a single isolated assessment. The PDAI activity score supplies the disease-activity measure used to evaluate that state. In general, a binary endpoint such as this makes the proportion reaching a defined outcome directly comparable between randomized groups. It does not, by itself, describe how quickly participants reached remission, how long remission lasted beyond the endpoint definition, or the full course of disease activity for each participant.

The posted primary result is 40.3% for rituximab and 9.5% for mycophenolate mofetil. The registry does not give further detail in the endpoint description about the exact operational rules for establishing sustained remission, such as the required assessment sequence. Those details are not reported in the registry record.

7. Results Posted in the Registry

• Mycophenolate Mofetil (MMF): 9.5% (6/63) versus 40.3% (25/62) on control; risk difference -30.8 percentage points (95% CI -45.0 to -16.6), risk ratio 0.24 (0.10–0.54); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Time to Initial Sustained Complete Remission

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Rituximab (RTX) vs Mycophenolate Mofetil (MMF): hazard ratio 4.83 (95% CI 1.97–11.81), reported p < 0.001 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically higher for Rituximab (RTX) vs Mycophenolate Mofetil (MMF) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Time to Protocol Defined Disease Flare

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Rituximab (RTX) vs Mycophenolate Mofetil (MMF): hazard ratio 0.15 (95% CI 0.06–0.39), reported p < 0.001 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically lower for Rituximab (RTX) vs Mycophenolate Mofetil (MMF) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary analyses point in a direction consistent with the primary endpoint: the reported time-to-event comparisons favor rituximab for reaching initial sustained complete remission and show a lower reported rate of protocol-defined disease flare. The registry also names outcomes covering corticosteroid dose, flare counts, health-related quality of life, adverse events, anti-drug antibodies, and immunoglobulin levels. Numerical analyses are posted for only some of these secondary outcomes; the record lists eight secondary outcomes but the analyzed results described in the registry include the two time-to-event comparisons.

These measures complement the primary remission percentage because they address timing, disease flares, treatment exposure, quality of life, and safety rather than the same binary endpoint alone. Their consistency in direction can strengthen the overall descriptive picture, but secondary findings do not substitute for the prespecified primary comparison. Each outcome may have different definitions, observation patterns, and analysis assumptions.

Multiplicity is important because testing many outcomes increases the chance that some results will appear statistically notable even when no corresponding effect exists. The registry record does not report a multiplicity adjustment or a hierarchy controlling the family of secondary tests. Therefore, secondary p-values should be interpreted as nominal findings unless the analysis plan establishes otherwise. The time-to-event results are evidence from the posted analyses, but they carry less confirmatory weight than the primary endpoint when the approach to multiple testing is not reported. Unreported secondary numerical results should not be inferred from the listed outcome names.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Cumulative Oral Corticosteroid Dose
• Total Number of Protocol Defined Disease Flares
• Time to Initial Sustained Complete Remission
• Time to Protocol Defined Disease Flare
• Change in Health-Related Quality of Life (HRQoL), as Measured by the Dermatology Life Quality Index (DLQI) Score
• Percentage of Participants With Adverse Events, Serious Adverse Events, and Corticosteroid-Related Adverse Events
• Percentage of Participants With Anti-Drug Antibodies (ADA)
• Percentage of Participants With Immunoglobulin (Ig) Levels Below Lower Limit of Normal (LLN)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary: each participant either met the sustained complete remission definition during the specified assessment period or did not. A group percentage expresses the share meeting that definition. The comparison of percentages is often presented as a risk difference, also called a difference in proportions. Its sign depends on which group is subtracted from which. The sponsor’s reported difference is presented as rituximab relative to mycophenolate mofetil and is positive; the simple recalculation is ordered as mycophenolate mofetil relative to rituximab and is negative.

What does a confidence interval describe?

A confidence interval is a range of values compatible with the observed data under the method’s assumptions. It conveys uncertainty around an estimate, rather than identifying a set of values that each have a particular probability of being true. For the reported primary difference, the 95% confidence interval is from 14.70 to 45.15 percentage points. Its endpoints are both on the positive side for rituximab relative to mycophenolate mofetil. The width of an interval reflects both the estimated effect and the information available for estimating it; it is not a measure of the range of individual participant outcomes.

What does the p-value add?

In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the analysis assumptions were correct. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The primary reported p-value is < 0.001. The simple unadjusted recalculation reports p < 0.001. Those values come from different analysis approaches, and both indicate that the corresponding test result is statistically incompatible with a no-difference null under its assumptions.

Why are the reported and recalculated comparisons not identical?

The sponsor’s analysis used the Cochran-Mantel-Haenszel method and reported a difference in proportion with a 95% confidence interval and a superiority result. The simple recalculation uses the posted group summaries without adjustment. Randomization was stratified by duration of illness, but the registry does not state which stratification variables were incorporated into the reported primary analysis beyond naming its method. An adjusted method and an unadjusted summary-based calculation can therefore produce estimates, intervals, and p-values that are not exactly the same. The registry record identifies no discrepancy requiring the sponsor analysis to be displaced.

How should the time-to-event results be read?

A time-to-event analysis considers both whether an event occurs and when it occurs during the observation period. A hazard ratio compares event rates over time under the analysis model; it is not a ratio of cumulative percentages or a direct difference in median weeks. For remission, the reported hazard ratio is 4.83 for rituximab versus mycophenolate mofetil, so the reported direction corresponds to a higher rate of reaching initial sustained remission in the rituximab group. For disease flare, the reported hazard ratio is 0.15, corresponding to a lower rate of flare in the rituximab group. These interpretations follow the stated group order and event definitions. The registry does not give the median value for either arm in these posted summaries, so a median time comparison cannot be recovered from those entries.

The log-rank method is reported for both time-to-event comparisons. In general, it compares event-time patterns between groups while accounting for the timing of events during follow-up. Interpretation depends on the event definition, follow-up, and analysis assumptions; further details about censoring rules or checks of model assumptions are not reported in the registry record.

Why can over-dispersion matter?

General statistical context: for count outcomes, variation can be greater than expected under a simple model that assumes a fixed mean-variance relationship. This is called over-dispersion. If present and ignored, uncertainty estimates can be too small, making intervals too narrow or test results too optimistic. The primary endpoint is reported as a percentage of participants, not as a count of repeated flares. The registry lists total number of protocol-defined disease flares as a secondary outcome, but does not provide a posted numerical result for it in the analyzed outcomes. The registry record does not report whether over-dispersion was assessed or how repeated flare counts were modeled.

11. Confidence Intervals and Precision

The primary reported 95% confidence interval ranges from 14.70 to 45.15 percentage points for the rituximab-minus-mycophenolate mofetil difference. Because the whole interval is above zero, the reported analysis supports a positive difference under its method. The interval is nevertheless broad enough that the exact magnitude remains uncertain. It should not be reduced to a single point estimate when judging the precision of the result.

The simple unadjusted recalculation gives the difference in the reverse order, mycophenolate mofetil minus rituximab: -0.308, with a 95% confidence interval from -0.45 to -0.166. The interval also excludes zero and has the same substantive direction once group order is made explicit. Its endpoints differ from the sponsor-reported interval because the calculations use different approaches. The registry record reports no discrepancy that would displace the sponsor’s analysis.

For time to initial sustained complete remission, the reported hazard ratio is 4.83, with a 95% confidence interval from 1.97 to 11.81. For time to protocol-defined disease flare, it is 0.15, with a 95% confidence interval from 0.06 to 0.39. Both intervals exclude the neutral hazard ratio of 1, but their widths indicate uncertainty about the precise relative event rate. A hazard-ratio interval does not directly give an interval for median time or an absolute probability at a particular time.

Confidence intervals describe sampling uncertainty under the analysis method; they do not account for every source of uncertainty, such as questions about endpoint definitions, missing data handling, or generalizability. Details on those issues are not reported in the registry record. Precision should therefore be considered alongside the trial’s population, analysis choices, and the limited information on endpoint handling.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations use the observed effect as a reference and show how the required sample size changes when planning for a smaller fraction of that effect. For the primary binary comparison, the figures are participants per arm: planning for 100% of the observed effect gives 30 participants per arm for 80% power and 40 participants per arm for 90% power; planning for 75% gives 60 and 79 participants per arm; planning for 50% gives 145 and 193 participants per arm. The time-to-event illustrations instead report total events, not participants per arm.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The time-to-event calculations use the Schoenfeld approach and report total events. The registry record does not report the original design assumptions used by the trial investigators or the basis for the planned enrollment.

In plain language, 80% power means that a study designed under the specified assumptions would have an 80% chance of detecting the target effect at the stated significance level if that effect were the true one. The 90% column uses a higher chance of detecting that target effect and consequently calls for more participants or events. Smaller target effects require more information, which is why the planning figures rise as the assumed effect becomes a smaller fraction of the observed effect. These are planning illustrations based on the observed result, not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.403; treatment proportion p₁ = 0.095; average p̄ = 0.249.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6117 = 1.1990.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5717 = 0.4811.
4. n = (1.1990 + 0.4811)² / (-0.3080)² = 29.8, rounded up to 30 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.403225806451613                          # control proportion
p1 <- 0.0952380952380952                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2383589)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 30 (80% power), 40 (90% power)
 75% of observed effect: n per arm = 60 (80% power), 79 (90% power)
 50% of observed effect: n per arm = 145 (80% power), 193 (90% power)
power.prop.test: 29.8 
Simulated power at n = 30 per arm: 0.820 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s own primary analysis reports a difference in proportions of 30.80 percentage points, with a 95% confidence interval from 14.70 to 45.15 and p < 0.001. It uses the Cochran-Mantel-Haenszel method. The separate simple recalculation from posted group summaries is unadjusted and expresses the difference in the reverse group order: -0.308, with a 95% confidence interval from -0.45 to -0.166 and p < 0.001. The difference in sign is a matter of comparison order, while both estimates indicate a higher remission percentage in the rituximab group.

The two analyses are not identical calculations, so small differences in their estimates and uncertainty measures are expected. The registry’s discrepancy indicator is false; no inconsistency is flagged between the reported result and the recalculation. Where a discrepancy is flagged, the sponsor’s own analysis takes precedence. In this record, the sponsor-reported analysis is the principal result, and the unadjusted calculation is best treated as a transparent check based on the posted group summaries rather than a replacement for the sponsor’s method.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies the primary endpoint and several secondary outcomes, but does not report how the study handled multiplicity across those outcomes. In general, when multiple hypotheses are tested, the chance of at least one false-positive result increases unless the testing strategy accounts for the number and ordering of comparisons. Without a reported hierarchy or adjustment, secondary p-values cannot be assumed to control the overall false-positive rate. The primary result remains the main confirmatory comparison identified in the registry, while the secondary results are best regarded as supportive or exploratory in the absence of further detail.

The record describes the primary analysis population as modified intent-to-treat. It includes participants in the stated intent-to-treat population who received any part of an infusion or oral study drug, excluding the 10 telemedicine participants. The reported primary group sizes are 62 for rituximab and 63 for mycophenolate mofetil. The registry record does not report the number of randomized participants excluded for other reasons, the disposition of all randomized participants, or the specific missing-data method for the primary endpoint.

Missing outcome data can affect a percentage endpoint if participants with unknown remission status are handled differently or differ systematically from those observed. General statistical practice may address this with prespecified assumptions and sensitivity analyses, but the registry record does not report whether such methods or analyses were used. The meaning of “sustained” remission also depends on operational assessment rules; those rules are not further described in the posted endpoint text.

For the time-to-event analyses, the registry names the log-rank method but does not give further details about censoring rules, losses to follow-up, or checks of analysis assumptions. These omissions do not invalidate the reported estimates, but limit independent assessment of how incomplete follow-up and multiple testing may influence the interpretation.

16. 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: infusion related reaction (4.5%), pulmonary embolism (2.9%), neutrophilic dermatosis (1.7%), haemophagocytic lymphohistiocytosis (1.5%), septic shock (1.5%).

The registry reports serious adverse events during the treatment safety summaries for 15 of 67 participants at risk in the rituximab group and 10 of 68 in the mycophenolate mofetil group. Other adverse events were reported for 42 of 67 and 41 of 68, respectively. These are descriptive counts in the recorded safety groups; they are not the primary efficacy population, and they should not be added to the primary analysis counts.

In safety follow-up, serious adverse events were reported for 4 of 66 in the rituximab follow-up group and 1 of 58 in the mycophenolate mofetil follow-up group. Other adverse events were reported for 2 of 66 and 3 of 58, respectively. The registry records 0 deaths in the rituximab group, 1 in the mycophenolate mofetil group, and 0 in each safety follow-up group. These figures describe what was recorded; they do not by themselves establish whether an event was caused by study treatment.

Listed serious adverse-event terms include infusion related reaction at 4.5%, pulmonary embolism at 2.9%, neutrophilic dermatosis at 1.7%, haemophagocytic lymphohistiocytosis at 1.5%, septic shock at 1.5%, and road traffic accident at 1.5%. The registry excerpt does not specify the denominator or further event-level details for those term percentages. Safety comparisons require attention to group definitions, time at risk, event severity, and attribution; the summary counts alone do not resolve those questions.

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

The posted data show a higher percentage achieving sustained complete remission by the primary analysis definition in the rituximab group than in the mycophenolate mofetil group. The sponsor-reported difference is 30.80 percentage points, and its 95% confidence interval is entirely on the positive side for rituximab relative to mycophenolate mofetil. The reported time-to-event analyses are also directionally consistent with more rapid initial sustained remission and a lower rate of protocol-defined flare in the rituximab group during the observed period.

These results describe the randomized groups under the registry’s endpoint definitions and analysis populations. They do not mean that every participant in one group had the same outcome, nor do they show that every participant in the other group failed to benefit. The confidence intervals make clear that the precise size of the group differences is uncertain. A p-value is not a measure of how important an outcome is to an individual, and statistical evidence does not by itself establish the balance of benefits and harms.

The findings apply most directly to participants who met the trial criteria: people with moderate-to-severely active pemphigus vulgaris requiring 60-120 milligrams per day of prednisone or equivalent, a confirmed diagnosis within the previous 24 months, and active disease at screening. The primary analysis excluded telemedicine participants. Generalizing beyond this population or beyond the treatment and follow-up periods requires additional evidence.

The registry safety summaries include serious and other adverse events and deaths, but do not establish causality or provide all context needed to compare individual risks. The record also does not report several details relevant to independent evaluation, including missing-data handling and multiplicity procedures. The statistical findings should therefore be read as evidence about the trial comparison, not as a universal conclusion about treatment or a substitute for individualized medical judgment.

18. Why This Trial Matters Statistically

Statistically, the trial is informative because it compares two active treatment strategies in a randomized, double-blind, double-dummy design. Randomization helps make groups comparable on average, while masking can reduce the influence of expectations on participant and investigator assessments. The matching placebo treatments address the different routes and schedules of the two active treatments. Stratification by duration of illness is also recorded as part of randomization.

The primary endpoint is a directly interpretable participant-level outcome: whether sustained complete remission, as evaluated by the PDAI activity score, was achieved through 52 weeks. The reported difference is large relative to its interval’s distance from zero, while the interval still communicates uncertainty about its magnitude. The accompanying time-to-event results examine timing and flare outcomes, offering different statistical views of disease course rather than merely duplicating the primary percentage.

The result also illustrates why analysis method and population definition matter. The sponsor’s Cochran-Mantel-Haenszel analysis and an unadjusted recalculation are closely aligned in direction but are not the same estimator. The primary population excludes telemedicine participants, and the registry does not explain the missing-data or multiplicity procedures. These details affect how confidently readers can extend the interpretation beyond the stated analysis.

Finally, the study’s active comparison is useful for understanding relative outcomes between the two assigned strategies in the enrolled population. It does not estimate outcomes against no treatment or against every alternative. The combination of a clear primary comparison, supporting time-to-event findings, and reported safety counts provides a statistical profile, while the unreported methodological details define important limits on how far that profile can be taken.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The trial enrolled a selected population with moderate-to-severely active pemphigus vulgaris requiring 60-120 milligrams per day of prednisone or equivalent. Participants also needed a confirmed diagnosis within the previous 24 months and evidence of active disease at screening. The results may not directly represent people with milder disease, a longer-standing diagnosis, or other clinical circumstances not covered by those criteria. The registry record does not provide enough detail to characterize how enrollment varied across centers or participant subgroups.

The primary analysis excluded the 10 telemedicine participants. This means the primary estimate is not based on all participants described in the trial population. The registry record does not report the reasons for this exclusion beyond identifying the group, nor does it provide a sensitivity analysis including them. It also does not report the handling of other missing endpoint data or the full participant disposition.

The primary endpoint’s description does not include the detailed operational rules used to determine sustained complete remission. The registry names the PDAI activity score, but does not provide the assessment schedule or the precise sequence required to classify remission as sustained. The posted secondary summaries also do not give median times for the time-to-event outcomes, limiting interpretation of absolute timing.

The registry record does not report the original sample-size justification, detailed missing-data procedures, multiplicity strategy, or further time-to-event assumptions. The follow-up includes a 48-week safety period, but the primary endpoint assessment ends at 52 weeks; the registry results should not be interpreted as longer-term efficacy estimates. Safety counts are descriptive and do not establish treatment causality.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil (MMF) in Participants With Pemphigus Vulgaris (PV) — NCT02383589.
• Registry record last updated 2020-11-10; status last verified 2020-10.
• Results first posted 2020-01-18.
• 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.

23. Record Summary

This completed Phase 3 randomized, double-blind, double-dummy, parallel-arm, active-comparator study compared rituximab with mycophenolate mofetil in participants with pemphigus vulgaris. The registry records enrollment of 135 and primary completion on 2018-11-28. Treatment lasted 52 weeks, with a planned 48-week safety follow-up.

The primary outcome was sustained complete remission evaluated by the PDAI activity score through 52 weeks, excluding telemedicine participants from the modified intent-to-treat analysis. The posted remission percentages were 40.3% for rituximab and 9.5% for mycophenolate mofetil. The reported difference was 30.80 percentage points, with a 95% confidence interval from 14.70 to 45.15 and p < 0.001.

Secondary time-to-event analyses favored rituximab by their reported directions. Serious adverse events and other safety outcomes were also recorded. Details of multiplicity handling and missing-data methods are not reported in the registry record.