A Study Comparing SB5 to Humira® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Comparing SB5 to Humira® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy (NCT02167139), a randomized phase 3 study. The primary outcome is American College of Rheumatology 20% Response Criteria (ACR20).

2. Clinical Question

The comparison is framed around the proportion meeting a prespecified response criterion, rather than an average change in a continuous measurement. The posted Week 24 response percentages are 72.4% for SB5 and 72.2% for Humira. The unadjusted risk-difference estimate is -0.002, with a 95% confidence interval from -0.083 to 0.078. That interval includes no difference and also allows for differences in either direction.

The clinical question therefore has two parts: what response proportions were observed, and how much uncertainty remains around their contrast? Similar point estimates alone do not establish that the treatments are equivalent. A formal equivalence or non-inferiority conclusion depends on a prespecified margin and an analysis plan; those details are not reported in the registry record.

The study also lists safety, tolerability, pharmacokinetics, immunogenicity, ACR50, and DAS28 among its areas of interest or outcomes. The central endpoint considered for the main comparison is specifically ACR20 at Week 24. Results from that endpoint should not be treated as a complete account of every clinical or safety question in the trial.

3. Trial Design

This was a Phase 3, randomized, quadruple-masked, parallel-group, multicentre clinical study comparing SB5 with Humira in participants with moderate to severe rheumatoid arthritis despite methotrexate therapy. The study is listed as completed. The registry record gives a start date of 2014-05 and primary completion of 2015-04, and reports enrollment of 544.

The two listed interventions were SB5, described as a proposed biosimilar to adalimumab, and Humira (adalimumab). Each was administered at 40 mg every other week by subcutaneous injection. Random allocation and masking are features intended to reduce the influence of participant or investigator expectations and systematic differences in treatment assignment. The record labels masking as quadruple but does not specify which groups of people were masked.

The design was parallel-group: participants were assigned to a treatment group for the initial comparison rather than crossing between treatments during the primary comparison period. The primary endpoint was the percentage of participants meeting ACR20 at Week 24. The primary outcome arms list 239 participants for SB5 and 237 for Humira. The reason that these endpoint denominators are smaller than the total enrollment is not reported in the registry record.

Secondary results include ACR20 at Week 52, with groups identified as continuing SB5, switching from Humira to SB5, or continuing Humira. ACR50 results are listed at Week 24 and Week 52, and DAS28 is named among the secondary outcomes. The registry record does not report the randomization ratio, detailed eligibility criteria, masking roles, original sample-size justification, or the full schedule of assessments. It also does not report a detailed statistical analysis plan or the population definitions used for each analysis.

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.

Randomised, Double-blind

Reasons for not completing this period:

Transition-extension

Reasons for not completing this period:

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 American College of Rheumatology 20% Response Criteria (ACR20), measured over Week 24.

The primary endpoint is the percentage of participants meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 24. It is a binary outcome: for each participant, the criterion is either met or not met, and the arm-level result is the proportion who met it. The registry record describes the unit as percentage of participants.

ACR20 is used as a response measure in rheumatoid arthritis studies. In general, a response criterion can make a treatment comparison easier to interpret as the share of participants reaching a defined level of improvement, rather than as a change in an average score that may obscure differences between individuals. The registry record does not provide a fuller operational definition of the criterion or the detailed rules for handling incomplete measurements.

For the primary endpoint, the posted proportions are 72.4% among 239 participants assigned to SB5 and 72.2% among 237 assigned to Humira. The risk-difference estimate is -0.002. This estimate compares the proportions on the absolute probability scale, where a value of zero represents no difference. Its 95% confidence interval, -0.083 to 0.078, expresses uncertainty around the contrast. The interval spans zero and includes values in both directions, so the point estimates should be read together with that uncertainty.

The endpoint is useful for comparing response proportions at the stated follow-up time, but it does not by itself describe all changes in disease activity, safety outcomes, durability, or individual experiences. Nor does a near-zero point estimate by itself prove equivalence; that interpretation requires a prespecified margin and appropriate analysis details, which are not reported in the registry record.

7. Results Posted in the Registry

• Humira (Adalimumab): 72.2% (171/237) versus 72.4% (173/239) on control; risk difference -0.2 percentage points (95% CI -8.3 to 7.8), risk ratio 1.00 (0.89–1.11); unadjusted two-proportion z-test p = 0.955.

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.

ACR20

• 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:
  • Humira (Adalimumab), Switch to SB5: 81.1% (86/106) versus 76.9% (163/212) on control; risk difference 4.2 percentage points (95% CI -5.1 to 13.6), risk ratio 1.06 (0.94–1.19); unadjusted two-proportion z-test p = 0.387.
  • Humira (Adalimumab), Continue as Humira: 71.2% (79/111) versus 76.9% (163/212) on control; risk difference -5.7 percentage points (95% CI -15.9 to 4.4), risk ratio 0.93 (0.81–1.06); unadjusted two-proportion z-test p = 0.260.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Humira (Adalimumab), Switch to SB5 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 Humira (Adalimumab), Continue as Humira and the control. The interval gives the range of effects that remain compatible with the data.

American College of Rheumatology 50% Response Criteria (ACR50)

• 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:
  • Humira (Adalimumab) at Week 24: 39.7% (94/237) versus 38.1% (91/239) on control; risk difference 1.6 percentage points (95% CI -7.2 to 10.3), risk ratio 1.04 (0.83–1.31); unadjusted two-proportion z-test p = 0.722.
  • SB5 (Proposed Biosimilar to Adalimumab) at Week 52: 49.1% (104/212) versus 38.1% (91/239) on control; risk difference 11.0 percentage points (95% CI 1.9 to 20.1), risk ratio 1.29 (1.04–1.59); unadjusted two-proportion z-test p = 0.019.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Humira (Adalimumab) at Week 24 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for SB5 (Proposed Biosimilar to Adalimumab) at Week 52 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes extend the primary response question to a later time point and to a different response threshold. ACR20 at Week 52 and ACR50 at Week 24 and Week 52 provide related but distinct views of response. DAS28 is also listed as a secondary outcome, but its result is not reported in the registry record.

Across the posted secondary comparisons, the pattern is not uniformly decisive. Some estimates are close to zero and have intervals spanning zero, while the ACR50 comparison for SB5 at Week 52 has an interval that does not span zero. At the same time, the Week 52 ACR20 contrasts have intervals that span zero. This variability means the secondary outcomes do not supply a single consistent confirmatory message that changes the interpretation of the primary Week 24 result.

These findings relate to the primary result by adding information about other response definitions and follow-up periods, not by replacing the primary endpoint. ACR50 represents a different response threshold from ACR20, and Week 52 observations arise later than the primary assessment. The Week 52 groups also distinguish participants who switched from Humira to SB5 from those who continued Humira, so their treatment histories differ from the initial randomized comparison.

Unadjusted secondary results carry less weight when several endpoints, time points, and contrasts are examined. Without a reported multiplicity strategy or testing hierarchy, an isolated result may reflect the number of opportunities to observe a nominally unusual finding. The registry record lists no reported secondary analyses. The secondary results are therefore best used as descriptive context, not as a basis for a separate confirmatory conclusion.

The Week 52 ACR20 results are based on fewer participants in the listed groups than the initial primary endpoint results, and the registry record does not explain the participant flow or missing-data handling. This makes it important not to assume that the later comparisons preserve all features of the initial randomized contrast. The record does not report the detailed analysis populations or the assumptions used for secondary outcome inference.

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

• ACR20
• American College of Rheumatology 50% Response Criteria (ACR50)
• Disease Activity Score Based on a 28 Joint Count (DAS28)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is a binary response outcome: participants either meet ACR20 at Week 24 or do not. An arm-level percentage describes the fraction meeting the criterion among the participants included in that result. The primary endpoint results list 239 participants for SB5 and 237 for Humira, with response percentages of 72.4% and 72.2%, respectively. Binary outcomes are often compared using a risk difference, a risk ratio, or an odds ratio. These measures answer related but distinct questions, so the scale should be clear when interpreting an estimate.

What does the risk difference represent?

The risk difference is the response proportion in one group minus the response proportion in the comparison group. Its natural reference value is zero, which represents equal proportions. For the primary comparison, the estimated risk difference is -0.002. The negative sign indicates the direction of the calculated contrast as defined for the comparison, but the estimate is small relative to its uncertainty. The 95% confidence interval is -0.083 to 0.078. Because that range includes zero, it does not isolate a direction of difference.

A risk difference is an absolute-scale measure: it describes the gap between proportions rather than a relative change. In clinical interpretation, absolute differences can be useful because they retain the outcome's original probability scale. The estimate must still be interpreted alongside its interval, the response definition, the follow-up time, and the design context. A near-zero estimate does not by itself establish that two treatments are equivalent.

How should the p-value be understood?

The unadjusted p-value for the primary comparison is 0.955. In general, a p-value is calculated under a null hypothesis and a statistical model; it describes the compatibility of the observed data, and data more extreme, with that model. It is not the probability that the treatments are the same, nor does it quantify the probability that a result is due to chance. The p-value also does not indicate whether a difference is clinically meaningful. The confidence interval conveys more direct information about the range of contrasts compatible with the data under the calculation's assumptions.

The comparison statistics are unadjusted recalculations from posted summary results, and the registry record lists no reported comparative analyses. An unadjusted calculation does not account for other covariates or for a broader set of tests. The registry record does not report an adjusted primary model, the exact analysis population, or the original analysis plan. These omissions limit the ability to determine whether the recalculations reproduce the trial's intended inferential procedure.

Why does the confidence interval matter?

A confidence interval combines an estimate with a measure of its sampling uncertainty. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision, given the model and data used. The primary interval crosses zero and includes negative and positive differences. It therefore does not rule out a range of possible contrasts in either direction. The interval is not a guarantee that the true value lies within its bounds, and it does not include uncertainty arising from design or reporting issues that the calculation does not model.

For binary outcomes, the amount of information depends on the numbers of participants and on how common the event is. It also depends on the comparison method and its assumptions. The posted endpoint counts and percentages make a simple unadjusted comparison possible, but they do not provide the individual-level data required to inspect covariate balance, missing outcome patterns, or model sensitivity.

What does over-dispersion mean in general?

Over-dispersion is a general statistical concern when observed variability is greater than a model assumes. It can make standard errors too small and confidence intervals too narrow if the model fails to account for the extra variability. The primary outcome is binary, and the registry record does not report an over-dispersion assessment or a model requiring such an assessment. The concept is relevant as a general reminder that uncertainty depends on model adequacy, not simply on the reported percentages.

How should the secondary comparisons be treated?

Several secondary outcomes or time points are listed, and more than one contrast is available for some outcomes. When many hypotheses are examined, the chance of at least one apparently notable result can increase. Multiplicity adjustments or a prespecified testing sequence can address this issue, but neither a correction strategy nor a hierarchy of secondary tests is reported in the registry record. The secondary comparisons should therefore be regarded as exploratory descriptions unless further analysis documentation establishes a confirmatory role.

The registry record lists ACR20 at Week 52, ACR50 at Week 24 and Week 52, and DAS28 among the secondary outcomes. The posted results include secondary response percentages and unadjusted recalculations for specified comparisons, but no reported analyses are listed. A result at a later time point may also reflect a different follow-up population or treatment history. The registry record does not provide enough detail to resolve all such issues or to identify the intended estimand for each secondary comparison.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.002, with a 95% confidence interval from -0.083 to 0.078. The interval crosses zero, the value representing equal response proportions. It includes contrasts favoring either group, so the observed point estimate does not establish a precise direction of effect.

A confidence interval is a range produced by a statistical procedure that reflects sampling uncertainty under its assumptions. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. The interval should not be read as a probability statement about the fixed true effect, nor does it account automatically for every uncertainty in study conduct, endpoint ascertainment, or analysis choices.

The limits are compatible with more than a negligible difference, depending on what difference would matter clinically. The registry record does not report a clinically important difference threshold, an equivalence margin, or a non-inferiority margin. It is therefore not possible to decide from this interval alone whether all differences within it would be considered acceptably small.

The primary response percentages are similar, but similarity of point estimates is not the same as high precision. Precision depends on the amount of information and the variability expected under the analysis. The confidence interval conveys this uncertainty more directly than a comparison of the percentages alone. The unadjusted p-value of 0.955 likewise does not substitute for an assessment of interval width or clinical relevance.

The confidence interval is an unadjusted recalculation from the posted summary data. The registry record lists no reported comparative analysis, and it does not provide an adjusted interval or details of the trial's intended analysis population. These limits matter when using the interval to characterize the inferential result.

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 report participants per arm for 80% power and participants per arm for 90% power. They are not totals across the arms and are not total-event counts. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The original sample-size assumptions and justification for the trial are not reported in the registry record.

The 80% power column means the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the assumed effect under those assumptions, if that effect and model were appropriate. The 90% column uses a higher target probability of detection, so it generally calls for more participants per arm. These are planning targets rather than guarantees for a future study.

The rows scale the assumed effect to 100%, 75%, or 50% of the observed effect. Smaller effects are harder to distinguish from no difference, so the planning calculation calls for more participants per arm as the assumed effect becomes smaller. This pattern is especially pronounced when the observed primary contrast is close to zero, as it is for the Week 24 ACR20 comparison. The resulting values should be read as illustrations of the stated calculation, not as a recommended design.

This is not observed power. Observed power is not a useful substitute for interpreting the estimate and confidence interval after a trial is complete. These calculations do not show what power the completed trial actually had under its original design, and they do not establish whether the original enrollment target was adequate. The registry record does not report the trial's own sample-size justification or its design assumptions.

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 = 0.724; treatment proportion p₁ = 0.722; average p̄ = 0.723.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6331 = 1.2409.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6331 = 0.5328.
4. n = (1.2409 + 0.5328)² / (-0.0023)² = 579,301.4, rounded up to 579,302 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 <- 0.723849372384937                          # control proportion
p1 <- 0.721518987341772                          # 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(2167139)
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 = 579,302 (80% power), 775,520 (90% power)
 75% of observed effect: n per arm = 1,029,204 (80% power), 1,377,811 (90% power)
 50% of observed effect: n per arm = 2,314,206 (80% power), 3,098,064 (90% power)
power.prop.test: 579301.4 
Simulated power at n = 579,302 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 multiple outcomes, assessment times, and comparison groups. The primary endpoint is ACR20 at Week 24, while secondary outcomes include ACR20 at Week 52, ACR50 at Week 24 and Week 52, and DAS28. Several Week 52 groups represent different treatment histories. Testing or examining many outcomes can increase the chance that at least one result appears notable by chance, even if no underlying difference exists.

Multiplicity is commonly addressed through a prespecified hierarchy, adjustment of significance thresholds, or another documented strategy. The registry record does not report such a strategy, nor does it identify a confirmatory sequence among secondary outcomes. The posted comparison p-values are unadjusted recalculations. They should not be treated as multiplicity-adjusted evidence, and an isolated unadjusted secondary result should be interpreted cautiously.

Missing-data handling is also not reported in the registry record. The primary endpoint results use denominators of 239 and 237, while total enrollment is 544. Week 52 secondary results list smaller group denominators. These differences do not reveal why participants are absent from a particular result, whether measurements were missing, whether participants discontinued, or how any missing outcomes were treated. No reason should be inferred from denominators alone.

The registry record does not report the analysis populations, such as whether results were based on all randomized participants, participants who received treatment, or participants with available endpoint data. It also does not report imputation methods, sensitivity analyses, or rules for intercurrent events. These details can affect the target question and the interpretation of response proportions.

Randomization supports a causal comparison when the analysis appropriately preserves the randomized groups and handles outcomes according to the study plan. Without analysis-population and missing-data details, the posted summary results cannot establish how fully the analysis followed that principle. The original statistical analysis plan, sample-size justification, and any interim-analysis plan are not reported in the registry record. No interim analyses should be assumed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (0.7%), acute myocardial infarction (0.4%), retinal oedema (0.4%), femoral hernia, obstructive (0.4%), escherichia urinary tract infection (0.4%).

The registry record reports serious adverse events for 9 of 268 participants in the SB5 group and 16 of 273 participants in the Humira group. The reported number of deaths is 0 in each group. These are counts and denominators from the posted safety results; they are not, by themselves, adjusted comparisons or evidence that a treatment caused an event.

The registry record also lists serious-event terms with percentages, including pneumonia at 0.7%, and acute myocardial infarction, retinal oedema, femoral hernia, obstructive, Escherichia urinary tract infection, and viral infection at 0.4% each. These entries describe reported terms and should not be interpreted as a complete account of all safety experience. The record does not provide a comparative statistical analysis of serious adverse events or explain how related events were grouped.

Safety interpretation depends on more than event counts. Relevant context can include exposure duration, event definitions, assessment procedures, participant characteristics, and how events were judged. Those details are not reported in the registry record. The denominators shown should therefore be kept with the counts, and the figures should be read descriptively rather than as proof of a safety difference or similarity.

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

The primary results show ACR20 response percentages of 72.4% for SB5 and 72.2% for Humira at Week 24. The unadjusted risk-difference estimate is -0.002, and its 95% confidence interval ranges from -0.083 to 0.078. The result is consistent with a small point-estimate contrast, but the interval allows for differences in either direction. The analysis does not establish that the treatments are identical.

The result also does not establish equivalence or non-inferiority. Such conclusions require a prespecified margin and an analysis designed to assess that margin. Neither the margin nor the trial's original analysis plan is reported in the registry record. A non-significant p-value is not a substitute for those elements.

The findings do not answer every question about treatment response. ACR20 at a single stated time point does not summarize all dimensions of rheumatoid arthritis, all secondary outcomes, or longer-term experience. The secondary response results provide additional context but are not reported as adjusted confirmatory analyses. DAS28 is named as a secondary outcome, but its result is not reported in the registry record.

Safety counts are also descriptive. Serious adverse events were reported in both groups, and deaths were reported as 0 in each group. The counts alone cannot determine whether a treatment caused or prevented events, and the record does not report a comparative safety analysis or all details needed for a full evaluation.

In general, a clinical trial result is interpreted by combining the endpoint definition, estimate, uncertainty, design, and analysis plan. Here, the primary comparison is a summary-data recalculation, while the registry record does not list a reported comparative analysis. The record also lacks details on missing data, analysis populations, multiplicity, and the original sample-size justification. The posted results therefore support a description of observed response proportions and their statistical uncertainty, but not a broader conclusion beyond the documented comparison.

17. Why This Trial Matters Statistically

This trial is statistically informative because its primary endpoint is a direct comparison of response proportions between randomized groups. It illustrates why the estimated contrast and its uncertainty should be considered together: the observed ACR20 percentages are very similar, yet the confidence interval still spans differences in either direction.

It also illustrates the distinction between a small observed difference and a formal equivalence conclusion. Equivalence and non-inferiority are not established merely by a high p-value or closely aligned point estimates. A prespecified margin and a suitable analysis are essential to interpret the evidence in those terms, and the registry record does not report such details.

The record offers a useful example of why readers should distinguish primary from secondary comparisons. Multiple response definitions, time points, and treatment histories appear among the outcomes. Without a reported multiplicity plan, secondary findings carry less confirmatory weight, particularly when one result stands out from a broader set of comparisons.

The planning illustrations also show how sample-size requirements depend on the assumed effect. When an observed contrast is very small, calculations aimed at detecting a smaller fraction of that contrast can produce very large participant requirements per arm. Those illustrations are not evidence of the completed trial's observed power or original design rationale.

Finally, the available registry results expose the importance of documentation. Reporting the analysis population, missing-data procedures, multiplicity approach, and original sample-size assumptions would make it easier to connect the posted estimates to the study's intended inferential claims. In their absence, the most defensible statistical account stays close to the response percentages, unadjusted contrast, confidence interval, and explicitly reported safety counts.

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 registry record does not include the original sample-size justification, a detailed statistical analysis plan, or an account of interim analyses. It therefore cannot establish which effect the trial was designed to detect, whether a formal equivalence or non-inferiority objective was prespecified, or whether analyses followed a particular testing sequence.

The primary comparison statistics are unadjusted recalculations from posted summary results, and no reported comparative analysis is listed. Individual-level data are not reported, limiting assessment of covariate balance, model choices, and sensitivity to alternative methods. The record also does not identify the analysis population or describe missing-outcome handling.

The primary endpoint denominators are smaller than total enrollment, and the Week 52 results have different group denominators. The registry record does not explain those differences or provide participant-flow details. Consequently, the later summaries cannot be assumed to represent the same population or treatment contrast as the initial randomized comparison.

Several secondary outcomes and comparisons are listed, but multiplicity procedures and a hierarchy of tests are not reported. This limits the confirmatory interpretation of individual secondary findings. The record names DAS28 as a secondary outcome, but its result is not reported in the registry record.

The safety information is also limited to posted event counts and selected serious-event terms. Exposure-adjusted analyses, event-assessment details, and a full comparative safety analysis are not reported. These limitations are specific to the information documented in the registry record and do not establish that the underlying trial lacked additional analyses or documentation.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study Comparing SB5 to Humira® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy — NCT02167139.
• Registry record last updated 2017-08-17; status last verified 2016-11.
• Results first posted 2017-01-19.
• 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

NCT02167139 is a completed Phase 3 randomized, quadruple-masked, parallel-group, multicentre study sponsored by Samsung Bioepis Co., Ltd. It compared SB5, described as a proposed biosimilar to adalimumab, with Humira in participants with moderate to severe rheumatoid arthritis despite methotrexate therapy. Enrollment was 544; the record gives a start date of 2014-05 and primary completion of 2015-04.

The primary endpoint was the percentage meeting ACR20 at Week 24. Posted response percentages were 72.4% for SB5 and 72.2% for Humira. The unadjusted risk difference was -0.002, with a 95% confidence interval from -0.083 to 0.078 and an unadjusted p-value of 0.955. Secondary outcomes include ACR20, ACR50, and DAS28, with some results and comparisons listed; DAS28 results are not reported in the registry record. Serious adverse events were reported for 9 of 268 participants in the SB5 group and 16 of 273 in the Humira group, with 0 deaths in each group.