A Study to Evaluate Ocrelizumab Compared With Placebo in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Ocrelizumab Compared With Placebo in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy (NCT00673920), a randomized phase 3 study. The primary outcome is Percentage of Participants With American College of Rheumatology (ACR) 20 Response.

2. Clinical Question

The clinical question is about the proportion reaching a prespecified response threshold, rather than the average change in a continuous measure. ACR20 requires at least 20% improvement in tender or swollen joint counts, together with 20% improvement in 3 of 5 additional criteria: physician's global assessment of disease activity, participant assessment of disease activity, patient assessment of pain on a visual analog scale, participant assessment of functional disability via a Health Assessment Questionnaire, and erythrocyte sedimentation rate. The endpoint is assessed at Week 24, during the placebo-controlled treatment period.

The study compared two Cycle 1 ocrelizumab regimens with placebo, all alongside methotrexate. The brief study summary describes subsequent treatment and re-randomization after the placebo-controlled period. Those later assignments do not form part of this Week 24 comparison; the endpoint uses the original randomization groups.

3. Trial Design

This was a phase 3, randomized, double-blind, parallel-group study. The registry describes it as international. It enrolled 314 participants and is listed as terminated. The reason for termination is not reported in the registry record, so the status alone does not establish why the study ended or whether the planned follow-up was completed.

The brief summary describes a planned 2:2:1 allocation across three Cycle 1 groups: ocrelizumab 200 mg intravenously on Days 1 and 15, ocrelizumab 400 mg intravenously on Day 1 with placebo on Day 15, or placebo on both days. All participants were to continue a stable dose of concomitant methotrexate, described as 7.5-25 mg per week. The primary endpoint results are reported for 64 participants in the placebo group, 117 in the ocrelizumab 400 mg group, and 131 in the ocrelizumab 200 mg Cycle 1 group.

The primary outcome is measured at Week 24, at the end of the placebo-controlled treatment period. The brief summary says that participants would then enter further treatment assignments: some groups would be re-randomized between ocrelizumab schedules, while the 400 mg group would receive a further 400 mg infusion. The registry lists later arm descriptions, but the primary endpoint table has no Week 24 results for those later treatment labels. They should not be treated as additional independent Week 24 comparison groups.

The primary endpoint population is the ITT population based on original randomization. The registry record does not report the detailed randomization procedure, concealment process, or full visit and follow-up schedule. It also does not report the reason for termination or a complete account of how many participants discontinued before endpoint assessment. These omissions limit what can be concluded about implementation and the flow of participants through the study.

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.

Only the first 6 of 8 groups are shown.

Baseline up to Week 48

Reasons for not completing this period:

Week 24 to Week 48

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population (original randomization)

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.

Population: Baseline characteristics not provided for Participants who were re-randomized at Week 24 (Cycle 2)

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With American College of Rheumatology (ACR) 20 Response, measured over Week 24.

The primary endpoint is the percentage of participants with an American College of Rheumatology 20 response at Week 24. ACR20 is a categorical measure: a participant either meets the response definition or does not. The definition requires at least 20% improvement in tender or swollen joint counts and 20% improvement in 3 of 5 additional measures covering clinician and participant assessments, pain, function, and erythrocyte sedimentation rate.

A composite response measure brings several aspects of rheumatoid arthritis assessment into one outcome. It can be easier to interpret as the proportion of participants who cross a defined threshold than as separate changes in each component. At the same time, a threshold does not show the size or pattern of change for every participant. Two people may both meet ACR20 while having different changes across joint counts, pain, function, or other criteria.

The endpoint is assessed at Week 24, during the placebo-controlled phase, and is reported for the ITT population based on original randomization. This aligns the comparison with the groups assigned at the start of treatment. It does not, by itself, describe later outcomes after re-randomization or establish how missing Week 24 assessments were handled. The detailed missing-data procedure is not reported in the registry record.

7. Results Posted in the Registry

• Ocrelizumab 400mg: 37.6% (44/117) versus 28.1% (18/64) on control; risk difference 9.5 percentage points (95% CI -4.6 to 23.6), risk ratio 1.34 (0.85–2.11); unadjusted two-proportion z-test p = 0.199.
• Ocrelizumab 200mg - Cycle 1: 52.7% (69/131) versus 28.1% (18/64) on control; risk difference 24.5 percentage points (95% CI 10.6 to 38.5), risk ratio 1.87 (1.23–2.86); 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.

Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ocrelizumab 400mg: 4.3% (5/117) versus 3.1% (2/64) on control; risk difference 1.1 percentage points (95% CI -4.5 to 6.8), risk ratio 1.37 (0.27–6.85); unadjusted two-proportion z-test p = 0.702.
  • Ocrelizumab 200mg - Cycle 1: 5.3% (7/131) versus 3.1% (2/64) on control; risk difference 2.2 percentage points (95% CI -3.5 to 8.0), risk ratio 1.71 (0.37–8.00); unadjusted two-proportion z-test p = 0.488.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ocrelizumab 400mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ocrelizumab 200mg - Cycle 1 and the control. The interval gives the range of effects that remain compatible with the data.

Change in DAS28 From Baseline

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ocrelizumab 400mg: mean -1.60 versus -0.79 on control; difference -0.81 (95% CI -1.26 to -0.36), standardized effect d = -0.60; z-test p = <0.001.
  • Ocrelizumab 200mg - Cycle 1: mean -1.67 versus -0.79 on control; difference -0.88 (95% CI -1.31 to -0.45), standardized effect d = -0.67; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Ocrelizumab 400mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Ocrelizumab 200mg - Cycle 1 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants Achieving an ACR50 Response

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ocrelizumab 400mg: 18.8% (22/117) versus 7.8% (5/64) on control; risk difference 11.0 percentage points (95% CI 1.3 to 20.7), risk ratio 2.41 (0.96–6.05); unadjusted two-proportion z-test p = 0.047.
  • Ocrelizumab 200mg - Cycle 1: 30.5% (40/131) versus 7.8% (5/64) on control; risk difference 22.7 percentage points (95% CI 12.5 to 33.0), risk ratio 3.91 (1.62–9.43); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Ocrelizumab 400mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Ocrelizumab 200mg - Cycle 1 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes give additional views of response and disease activity at Week 24. The posted numerical results include DAS28 remission, change in DAS28 from baseline, and ACR50 response. In broad terms, the response percentages and mean DAS28 changes show a pattern in which the ocrelizumab groups have higher response proportions or more negative mean change estimates than placebo. These measures complement the primary ACR20 endpoint because they use different thresholds or summarize change on a scale.

They do not independently confirm the primary result. DAS28 remission is a stricter categorical threshold than a change score, while ACR50 requires a greater response threshold than ACR20. Change in DAS28 preserves more information about the magnitude of score change but represents a different outcome. Differences among these measures are not inherently contradictory; each captures a distinct feature of the observed results.

The registry also lists outcomes including EULAR response rates, ACR70 response, and changes in individual ACR core-set parameters, including C-reactive protein concentration and erythrocyte sedimentation rate. Detailed numerical results for outcomes beyond those summarized in the posted results are not reported in the registry record. The listed outcome names alone do not establish their direction or size.

The secondary comparisons are unadjusted. When multiple outcomes and treatment comparisons are examined, the chance of seeing an apparently notable result by chance can increase. Without a reported multiplicity procedure, these p values and intervals should be treated as exploratory rather than as a collection of confirmatory tests. The endpoint hierarchy and analysis plan are not reported in the registry record. The secondary results can help describe consistency and context, but they carry less evidential weight than a prespecified primary analysis interpreted under a known analysis plan.

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

• Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6)
• Change in DAS28 From Baseline
• European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders)
• Percentage of Participants Achieving an ACR50 Response
• Percentage of Participants Achieving an ACR70 Response
• Change From Baseline in the Individual Parameters of the ACR Core Set
• Change From Baseline in the Individual Parameters of the ACR Core Set: C-Reactive Protein (CRP) Concentration
• Change From Baseline in the Individual Parameters of the ACR Core Set: Erythrocyte Sedimentation Rate (ESR)

9. Statistical Interpretation

10. Statistical Methods Explained

The registry describes a randomized, double-blind, parallel-group study. Randomization assigns participants to treatment groups by chance, which is intended to make the groups comparable at the start on average. Double blinding means that participants and investigators were masked, as stated in the record; details of who else was masked and how masking was maintained are not reported in the registry record. A parallel-group design compares groups assigned to different regimens over the same study period.

What does the primary response measure?

ACR20 is a binary endpoint. Each participant is classified according to whether the response criteria are met at Week 24. The posted percentages summarize the share of participants classified as responders in each original randomization group. A percentage is a group summary: it does not reveal the response profile of each participant, nor which individual components of the composite were most responsible for meeting the threshold.

The endpoint is defined using joint counts and a set of additional disease activity, pain, function, and inflammation measures. Its threshold helps make the outcome clinically interpretable as a response category. However, any threshold discards information about the degree of improvement above or below that cut point. Other outcomes, such as changes in DAS28 and ACR50, provide complementary perspectives but do not replace the primary endpoint.

How should the risk difference be read?

The risk difference compares the response proportion in an ocrelizumab group with the response proportion in placebo. A value above zero represents a higher observed response proportion in the ocrelizumab group; a value below zero represents a lower observed response proportion. The posted estimates are expressed as proportions rather than percentage points. The confidence interval describes uncertainty around the estimated difference. If it includes zero, the interval includes no difference under this measure; if it lies entirely to one side, it excludes zero for that unadjusted interval.

The registry also includes unadjusted p values for these comparisons. A p value assesses how compatible the observed data are with a specified null model, given the calculation's assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The detailed statistical plan and any sponsor-adjusted analyses are not reported in the registry record. The comparisons are unadjusted calculations from the posted summary statistics.

What do the confidence intervals add?

A confidence interval gives a range of values compatible with the data under the method used to calculate it. It communicates estimation uncertainty, which a point estimate alone cannot show. Wider intervals indicate less precision than narrower intervals. For binary endpoints, the group percentages and the confidence interval for a group difference answer related but distinct questions: the first describes each group's response estimate, while the latter estimates the contrast between groups.

Confidence intervals do not incorporate every source of uncertainty. In particular, they do not automatically account for multiple endpoints or comparisons, missing outcome data, or departures from the model used to calculate them. Those issues require details from the analysis plan and the underlying data. The record does not describe a multiplicity procedure or the missing-data approach.

What is the role of the reported analysis population?

The primary population is identified as ITT based on original randomization. An intention-to-treat approach generally retains participants in the groups to which they were initially assigned, preserving the randomized comparison. The registry's population label does not explain exactly how participants without a Week 24 assessment were handled, whether imputation was used, or whether all randomized participants contributed to each posted estimate. Those details are not reported in the registry record.

The Week 24 primary results are attached to the original Cycle 1 groups. After the placebo-controlled period, the study summary describes re-randomization for some participants and further ocrelizumab dosing. Later arm labels therefore refer to subsequent treatment sequences, not independent original randomized groups for the primary endpoint. This distinction matters when reading safety and follow-up summaries, where the listed groups include those later sequences.

How should the planning illustrations be interpreted?

The sample-size illustrations use the observed effect as a starting point and show planning scenarios for detecting the full observed effect or a stated fraction of it. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The figures are participants per arm for these non-time-to-event outcomes. The trial's original sample-size justification and design assumptions are not reported in the registry record.

These illustrations are distinct from the trial's actual analysis. They do not establish the trial's power after completion, and the trial should not be described as having observed power calculated from its results. The planning values change with the assumed effect size and are intended to show how design requirements depend on the effect researchers want to detect. A smaller target effect generally requires more participants to distinguish it from random variation under the stated assumptions.

The registry record lists no reported analyses in the secondary outcome entries. That absence should not be filled in by assuming a model, adjustment, or analysis population beyond what is explicitly stated. The statistical method for the trial's original sponsor analyses is not reported in the registry record.

11. Confidence Intervals and Precision

The primary endpoint table presents both group-specific estimates and comparisons with placebo. The 95% confidence intervals around the group response percentages show uncertainty in each response estimate. The intervals for placebo, ocrelizumab 400 mg, and ocrelizumab 200 mg Cycle 1 are 17.1 to 39.1, 28.8 to 46.4, and 44.1 to 61.2. They give a sense of the range of values compatible with the observed data under the interval method.

For the risk difference, the ocrelizumab 400 mg comparison has a 95% confidence interval from -0.046 to 0.236. This crosses zero and spans values on both sides of no difference. The ocrelizumab 200 mg Cycle 1 comparison has an interval from 0.106 to 0.385, which does not include zero. Both intervals have meaningful width, so the point estimates should not be read as exact values for the underlying group contrast.

A confidence interval is not a guarantee that the true value lies within the displayed bounds, nor is it a probability statement about a particular treatment effect. Its interpretation depends on the statistical procedure and assumptions. In repeated use under those assumptions, intervals constructed in this way have their stated coverage property. The registry does not report full details of the sponsor's interval calculation.

The posted estimates also have limitations that intervals cannot repair. The record does not report the handling of missing Week 24 data, adjustments for multiple comparisons, or a complete sponsor analysis plan. The intervals describe statistical uncertainty from the posted calculations, not these broader design and analysis uncertainties. Precision should therefore be considered together with the registry's reporting gaps.

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 sample-size table and curve are planning illustrations based on the observed effect, not a report of the trial's original design calculation. For these outcomes, the figures are participants per arm. The registry's planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; each scenario uses the stated fraction of the observed effect as the effect to detect. The original trial sample-size justification and assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm that the illustration estimates would be needed to have an 80% chance of detecting the assumed effect under those planning conditions, if the effect and assumptions were correct. The 90% column expresses the analogous planning target with a higher chance of detection. These are prospective design concepts: they describe how a future study might be planned, not what the completed trial achieved.

Rows showing 100%, 75%, or 50% of the observed effect represent different assumed effect sizes for planning. The smaller the effect researchers want to detect, the more participants the illustration generally requires. The sample sizes are not a claim that these effects are true, and the calculations are not observed power. The curve should be read as a visual representation of the same planning relationship, not as additional evidence about the trial outcome.

These calculations use equal allocation even though the brief study summary describes a planned 2:2:1 allocation. They are therefore illustrative rather than a reconstruction of the original design. No justification for the actual allocation or original enrollment target is reported in the registry record.

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 = 0.281; treatment proportion p₁ = 0.376; average p̄ = 0.329.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6643 = 1.3020.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6609 = 0.5562.
4. n = (1.3020 + 0.5562)² / (0.0948)² = 384.1, rounded up to 385 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 <- 0.28125                          # control proportion
p1 <- 0.376068376068376                          # 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(673920)
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 = 385 (80% power), 514 (90% power)
 75% of observed effect: n per arm = 671 (80% power), 898 (90% power)
 50% of observed effect: n per arm = 1,480 (80% power), 1,980 (90% power)
power.prop.test: 384.1 
Simulated power at n = 385 per arm: 0.802 (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. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint and multiple secondary outcomes. It does not report how the statistical plan controlled the risk of false-positive findings from examining multiple endpoints, treatment comparisons, or analyses. No multiplicity adjustment is shown in the posted comparisons. The unadjusted p values should therefore not be interpreted as though they were part of a reported family-wise testing procedure, and the nominal results do not by themselves establish confirmatory evidence across outcomes.

The record also does not report whether there were interim analyses, stopping rules, or planned adaptations. The study status is terminated, but the reason and the decision process behind termination are not reported. It would be inappropriate to infer that termination followed a particular efficacy, safety, or operational rule from the status alone.

The primary population is labeled ITT based on original randomization, but the registry does not explain how missing Week 24 outcomes were handled. It does not state whether missing values were imputed, whether a particular nonresponder rule was used, or how many participants lacked an endpoint assessment. The group denominators in the primary outcome table are visible, but they do not supply a complete account of missingness or participant flow.

The record does not provide a detailed statistical analysis plan, including model specifications, covariate adjustment, sensitivity analyses, or the sponsor's full inferential procedure. The comparisons are unadjusted calculations from posted summary statistics. The registry reports no analysis entries for the listed secondary outcomes. These gaps constrain interpretation: the estimates can be described as posted, but their relation to any planned confirmatory analysis cannot be established from the registry record.

15. 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 0.05% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchiectasis (10.3%), mycobacterium abscessus infection (3.4%), dyspnoea (3.4%), uterine leiomyoma (3.4%), urinary tract infection (1.6%).

The safety summary lists the number at risk and the number affected by serious adverse events and other adverse events for each treatment sequence, along with deaths. These are counts, not adjusted comparisons. For the original Cycle 1 groups, the serious adverse event counts are 5 of 64 for placebo, 3 of 117 for ocrelizumab 400 mg, and 2 of 131 for ocrelizumab 200 mg. The corresponding counts for other adverse events are 32 of 64, 59 of 117, and 80 of 131. The registry also lists later sequence groups, which should be distinguished from the original Week 24 endpoint groups.

The safety table reports one death in the ocrelizumab 400 mg/ocrelizumab 400 mg sequence and zero in the other listed groups. It also lists serious adverse event terms and associated percentages, including bronchiectasis, Mycobacterium abscessus infection, dyspnoea, uterine leiomyoma, urinary tract infection, and influenza-like illness. The registry summary does not establish that a treatment caused an event. It also does not provide a detailed exposure-adjusted analysis or a complete account of event timing and duration in the information.

Counts should be read in relation to their group denominators and the treatment sequence labels. They do not provide, by themselves, a basis for comparing risk across groups when exposure and follow-up details are not available. The posted figures are descriptive and should not be interpreted as a safety conclusion.

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

The posted Week 24 results show different observed ACR20 response proportions across the original randomized groups. The unadjusted comparison for ocrelizumab 200 mg Cycle 1 has a risk-difference interval above zero, while the interval for ocrelizumab 400 mg includes zero. The confidence intervals communicate the uncertainty around these estimates; neither the percentages nor the p values alone describe the full evidential picture.

These results do not mean that every participant in a group had the same experience. ACR20 is a threshold-based composite: it records whether the response definition was met, not the detailed improvement in each component. The secondary results offer related but distinct summaries, and the registry record does not report numerical results for every listed outcome.

The findings also do not settle questions about long-term outcomes or later treatment schedules. The primary endpoint is at Week 24, before the subsequent assignments described in the study summary. The registry status is terminated, but the reason for termination is not reported. The record does not give enough information to infer why the study ended or how termination affected follow-up.

The posted comparisons are unadjusted calculations, and the registry record does not report a multiplicity procedure, detailed missing-data handling, or the sponsor's complete statistical plan. Those omissions matter when assessing how much weight to place on multiple endpoint results and how representative the analyzed participants are of all randomized participants. The results should therefore be understood as estimates from the posted registry information, not as a complete substitute for a full analysis report.

Nothing in these statistical summaries alone establishes a clinical recommendation, a definitive causal conclusion, or an individual outcome. They show the reported group-level response and safety counts, together with uncertainty and reporting limitations. Interpretation requires attention to the endpoint definition, the original randomization groups, the confidence intervals, and the unreported analysis details.

17. Why This Trial Matters Statistically

This trial illustrates why the contrast between an endpoint estimate and its uncertainty matters. A response percentage gives a concise summary, but the risk difference and its confidence interval address the comparison directly. For one ocrelizumab regimen, the posted interval includes zero; for the other, it lies above zero. The distinction is visible in the interval, not merely in the ordering of the group percentages.

It also demonstrates the role of endpoint choice. ACR20, ACR50, DAS28 remission, and change in DAS28 capture related but nonidentical aspects of response. A threshold endpoint is easy to express as a proportion, while a continuous change score describes average movement on a scale. Agreement in broad direction can be informative, but multiple endpoints do not become independent confirmation simply because they point in a similar direction.

The trial's later re-randomization makes it important to keep treatment sequence and original allocation separate. Week 24 efficacy comparisons use the original groups; later safety groups include subsequent treatment sequences. Reading all labels as though they represented interchangeable arms would blur the study phases and the populations being summarized.

Finally, the registry shows how reporting gaps shape statistical interpretation. The primary population is named, and several estimates are posted, but detailed analysis methods, multiplicity handling, missing-data procedures, and the termination reason are not reported. Statistical literacy includes recognizing both what the numerical results show and what a registry summary cannot establish.

18. 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 is listed as terminated, but the reason for termination is not reported in the registry record. The record does not explain whether termination affected planned recruitment, treatment, or follow-up, so its implications for the results cannot be determined from the status alone.

The primary endpoint is reported at Week 24, while the brief summary describes later treatment and re-randomization. The primary results are tied to original randomization and do not describe outcomes for all later treatment sequences. The safety summary includes those later sequence groups, but the details needed to compare exposure periods and follow-up are not reported.

The record gives an ITT population label but does not describe missing Week 24 data, participant flow by outcome, or the procedure used for incomplete assessments. The analysis method and any covariate adjustments are also not reported. This makes it difficult to assess how closely the posted estimates follow the intended analysis plan.

The listed secondary outcomes are numerous, yet multiplicity control is not reported. The displayed p values are unadjusted, and secondary results should not be treated as independent confirmation of the primary comparison. Numerical results are not available in the registry record for every secondary outcome listed.

Finally, the safety counts are descriptive. The registry summary does not provide detailed timing, duration, exposure-adjusted rates, or causal attribution for events. The trial's sample-size justification is not reported; planning illustrations based on observed effects do not resolve that gap or reconstruct the original design rationale.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study to Evaluate Ocrelizumab Compared With Placebo in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy — NCT00673920.
• Registry record last updated 2020-12-04; status last verified 2020-11.
• Results first posted 2020-12-04.
• 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.

22. Record Summary

This phase 3 study randomized 314 participants with active rheumatoid arthritis and an inadequate response to methotrexate. It compared Cycle 1 ocrelizumab regimens with placebo, alongside stable-dose methotrexate, in a double-blind, parallel-group design. The primary endpoint was Week 24 ACR20 response in the ITT population based on original randomization.

The registry posts response estimates and unadjusted comparisons for the two ocrelizumab groups versus placebo. The 200 mg Cycle 1 comparison has a risk-difference confidence interval above zero; the 400 mg comparison's interval includes zero. Secondary outcomes provide additional, nonidentical measures, and the record includes descriptive adverse-event counts.

The study is listed as terminated. The reason, detailed statistical plan, multiplicity procedure, and missing-data handling are not reported in the registry record. The posted results should be interpreted with those limitations in view.