This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of Tocilizumab (RoActemra/Actemra) Versus Adalimumab in Patients With Rheumatoid Arthritis (NCT01119859), a randomized phase 4 study. The primary outcome is Change From Baseline to Week 24 in the Disease Activity Score 28 (DAS28).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01119859 |
| Phase | Phase 4 |
| Condition | Rheumatoid Arthritis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 326 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Patients with rheumatoid arthritis who were intolerant of methotrexate or for whom continued methotrexate treatment was considered inappropriate. The primary analysis population was defined as randomized patients who received at least 1 dose of tocilizumab or adalimumab and had at least 1 efficacy assessment.
Intervention
Tocilizumab 8 mg/kg intravenously every 4 weeks, paired with placebo injections on the adalimumab schedule. The registry describes 6 infusions and 12 placebo injections.
Comparator
Adalimumab 40 mg subcutaneously every 2 weeks, paired with placebo infusions on the tocilizumab schedule. The registry describes 12 injections and 6 placebo infusions.
Primary question
How did mean DAS28 change from baseline to Week 24 in each randomized treatment group? The index combines joint counts, an inflammation marker, and a patient global assessment; a negative change indicates improvement. The registry reports adjusted mean changes and confidence intervals, but a direct between-group estimate and test for the primary endpoint are not reported in the registry record.
The comparison concerns two monotherapy regimens in the specified rheumatoid arthritis population. Matching placebo administrations were used to support blinding despite different routes and schedules. The registry says the study nurse was unblinded because of the treatment administration, while the investigator and patient remained blinded. That distinction matters when considering how treatment assignment could have been known during trial conduct.
3. Trial Design
This was a randomized, double-blind, parallel-group Phase 4 study sponsored by Hoffmann-La Roche. The registry reports enrollment of 326 and a completed study. The recorded study start is 2010-05, and primary completion is recorded as 2012-01. Treatment was anticipated to last 24 weeks.
Participants were assigned to one of two active monotherapy regimens. Tocilizumab was given intravenously every 4 weeks with subcutaneous placebo every 2 weeks; adalimumab was given subcutaneously every 2 weeks with intravenous placebo every 4 weeks. The placebo administrations made the treatment schedules more similar to participants and investigators, although the study nurse was unblinded because of the administration procedures.
The primary outcome was change from baseline to Week 24 in DAS28, analyzed as a continuous measure. Its posted estimates are means with 95% confidence intervals. The primary population is described as an intent-to-treat population, but with the additional requirement that patients received at least 1 dose and had at least 1 efficacy assessment. The registry does not report a separate protocol-level description of how participants without an efficacy assessment were handled.
The record also lists secondary outcomes concerning DAS28 remission and low disease activity, ACR improvement, and EULAR response. The posted secondary results include remission, low disease activity, and EULAR good response. Detailed inferential analyses for the primary outcome are not reported in the registry record, so the posted arm-specific estimates should not be mistaken for a complete account of the trial's planned 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.
Overall Study
| Stage | Tocilizumab 8 mg/kg | Adalimumab 40 mg |
|---|---|---|
| STARTED | 163 | 163 |
| COMPLETED | 139 | 133 |
| NOT COMPLETED | 24 | 30 |
Reasons for not completing this period:
| Reason | Tocilizumab 8 mg/kg | Adalimumab 40 mg |
|---|---|---|
| Adverse Event | 9 | 10 |
| Death | 2 | 0 |
| Insufficient therapeutic response | 7 | 14 |
| Refused treatment | 3 | 6 |
| Failure to return | 3 | 0 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of tocilizumab or adalimumab and had at least 1 efficacy assessment.
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.
| Characteristic | Unit | Tocilizumab 8 mg/kg | Adalimumab 40 mg | Total |
|---|---|---|---|---|
| Participants analysed | 163 | 162 | 325 | |
| Age Continuous | years | 54.4 (SD 12.95) | 53.3 (SD 12.43) | 53.9 (SD 12.67) |
| Sex: Female, Male: Female | Participants | 129 | 133 | 262 |
| Sex: Female, Male: Male | Participants | 34 | 29 | 63 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline to Week 24 in the Disease Activity Score 28 (DAS28), measured over Baseline to Week 24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Units on a scale |
| Endpoint classification | Continuous Endpoint |
DAS28 is a continuous index intended to summarize rheumatoid arthritis disease activity using information from swollen and tender joint counts, erythrocyte sedimentation rate, and the patient's general health assessment. The registry describes counts across 28 joints and a global assessment recorded on a visual analog scale. Higher DAS28 values indicate higher disease activity, while a negative change from baseline indicates improvement.
The primary endpoint is the change in DAS28 from baseline to Week 24. Analyzing change retains information about the degree of movement in the score rather than reducing outcomes to categories such as remission or no remission. That can make it useful for comparing average changes between groups, while still requiring attention to uncertainty and to the meaning of a group average for individual patients.
The registry states that the primary analysis was adjusted for stratification factors: duration of rheumatoid arthritis, categorized as ≤ 2 years and > 2 years, and region, categorized as US and non-US. The reported arm estimates are means with 95% confidence intervals. The scale ranges from 0 to 10, and an ESR value of 0 mm/hr was set to 1 mm/hr for the score calculation. Those details define how the index and the primary change measure were constructed.
The endpoint is a disease activity measure, not a direct measure of every aspect of health, function, or safety. It also does not by itself establish whether an observed group difference is clinically important; that judgment requires context beyond the means alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the primary endpoint, the posted mean change was -3.3 DAS28 units for tocilizumab 8 mg/kg, with a 95% confidence interval from -3.57 to -3.02. For adalimumab 40 mg, the posted mean change was -1.8, with a 95% confidence interval from -2.1 to -1.55. Since the registry defines a negative change as improvement, both arm-level estimates indicate a decrease in mean DAS28 over the assessment period. The point estimates indicate a larger mean reduction in the tocilizumab group, but the posted arm-specific estimates are not a direct estimate of the difference between groups.
A confidence interval describes uncertainty around an estimated mean under the analysis assumptions; it is not a range containing every participant's response. These intervals help convey the precision of each arm's mean estimate. They do not replace a confidence interval for the treatment contrast, which is not reported in the registry record for this primary outcome. Nor should the overlap or separation of separate arm intervals be used as a substitute for the trial's direct comparative analysis.
The primary analysis is described as adjusted for duration of rheumatoid arthritis and region. The registry gives the adjustment factors, but it does not report the model details or a comparative test result. The posted primary estimates therefore support a descriptive reading of each group's average change, but they do not disclose the full inferential result for the randomized comparison. A sponsor-reported analysis of that contrast is not reported in the registry record.
The secondary results are consistent in direction with the primary arm-level pattern: the posted response proportions are higher in the tocilizumab arm for remission, low disease activity, and EULAR good response. These are categorical outcomes and are not interchangeable with the continuous change in mean DAS28. They describe whether participants met specified response definitions at the assessment point, whereas the primary endpoint summarizes average change.
Some secondary comparisons have unadjusted recalculated P values listed as <0.001. Such values do not account for the number of outcomes examined, and the registry does not report adjusted secondary tests. They should therefore be treated as exploratory rather than as a substitute for a prespecified multiplicity-controlled analysis. The registry's posted data show outcome estimates and uncertainty to varying degrees, but do not report a complete statistical analysis plan or the full set of primary and secondary comparative results.
9. Statistical Methods Explained
Statistical interpretation begins with the type of outcome. DAS28 change is continuous, so the registry reports a mean for each treatment group and a 95% confidence interval. Remission and low disease activity are categorical outcomes, so their results are expressed as percentages of patients meeting a defined threshold. These different summaries answer related but distinct questions: average movement in a score versus the proportion meeting a response definition.
What does a confidence interval describe?
As a general statistical explanation, a confidence interval expresses the uncertainty of an estimate under the assumptions of the method used. A narrower interval indicates greater precision for that estimate; a wider interval indicates less precision. The primary endpoint intervals apply to the mean change within each arm. They are not intervals for the difference between the randomized groups, and they do not show the range of individual participant outcomes.
The primary endpoint uses a 95% confidence interval. The registry describes the mean change in DAS28 from baseline to Week 24 and says that the analysis was adjusted for stratification factors. The posted values do not include the comparative adjusted mean difference, its confidence interval, or its P value. Separate arm estimates can describe what was observed in each group, but a direct treatment comparison is the quantity needed to quantify the difference attributable to assignment in the trial analysis.
Why distinguish arm estimates from a treatment contrast?
In a randomized comparison, the scientific question is generally about the difference between groups, not simply whether change occurred within each group. Each group can improve over time for reasons that are not specific to its assigned treatment, including background changes and trial participation. A direct between-group estimate compares outcomes while preserving the randomized design. Because that estimate is not reported for the primary outcome in the registry record, it should not be reconstructed by subtracting the posted means.
The registry says the primary analysis adjusted for duration of rheumatoid arthritis and region. Adjustment can account for the trial's stratification factors in the analysis, but the specific model, covariance assumptions, and handling of missing observations are not reported in the registry record. The arm-level posted means should be read alongside that caveat rather than assumed to be unadjusted or to reproduce a particular model.
How should categorical outcomes be read?
For remission, low disease activity, and EULAR good response, the registry gives the percentage meeting the endpoint in each group. A risk difference compares the proportions on an absolute scale; a confidence interval for that difference describes uncertainty in the comparison. The secondary comparison records also include unadjusted P values. These are recalculated from posted summary counts and are not reported sponsor analyses. They are useful as descriptive statistical summaries, but they do not establish that the analysis was prespecified or adjusted for testing multiple outcomes.
The displayed secondary estimates include relative measures as well as absolute measures. In general, relative measures compare the frequency of an outcome across groups, whereas risk differences describe the absolute separation in proportions. Each measure has a different scale and interpretation. The absolute outcome percentages remain important context, and a relative measure should not be read without considering the observed proportions and the study population.
What do the sample-size illustrations mean?
The planning calculations are illustrations based on the observed effect, not the trial's own sample-size justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. The rows describe planning for 100%, 75%, or 50% of the observed effect, and the entries are participants per arm for 80% power or participants per arm for 90% power. These figures are not observed power and do not show that the trial was designed using those assumptions. The trial's own sample-size justification is not reported in the registry record.
As a general statistical point, planning estimates depend on assumptions about the effect size, outcome variability or event frequency, significance level, allocation, and analysis method. If the effect used for planning is drawn from the observed trial estimate, the illustration is conditional on that estimate and can be optimistic or otherwise unrepresentative of a future study. These calculations should be interpreted as scenarios rather than as a retrospective verdict on the trial's adequacy.
Why does over-dispersion matter in general?
Over-dispersion is a general concern when outcome variability exceeds what a statistical model assumes. If it is ignored, standard errors can be too small and confidence intervals or tests can appear more certain than warranted. The primary outcome is a continuous score, and the registry does not report an over-dispersion assessment or a model diagnostic. This general concept is therefore relevant as a reminder about assumptions, not as a claim that over-dispersion occurred in this trial.
Across all outcomes, the registry record does not report a complete account of the model specifications, missing-data procedures, or multiplicity strategy. That limits independent evaluation of how the full family of results was analyzed. The safest reading separates reported arm summaries, unadjusted recalculations, and analyses that are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when statistical conclusions are drawn from several outcomes, comparisons, or analysis choices. Each additional test creates another opportunity for a result to cross a conventional significance threshold by chance. A prespecified hierarchy, family-wise error adjustment, or another stated strategy can control how findings are interpreted across a group of tests. Such a strategy is not reported in the registry record.
The record lists several secondary outcome domains, and it posts results for remission, low disease activity, and EULAR good response. The unadjusted comparison values for these results are recalculated summaries based on the posted counts; they are not reported sponsor analyses. Without a reported testing hierarchy or multiplicity adjustment, their P values carry less confirmatory weight than a result from a prespecified analysis that accounts for multiple testing. The registry does not report sponsor-reported comparative analyses for these outcomes.
Missing-data handling is also not reported in the registry record. The primary analysis population is described as randomized patients who received at least 1 dose and had at least 1 efficacy assessment. That definition identifies who could enter the stated population, but it does not explain how missing Week 24 measurements, withdrawals, or incomplete assessments were handled in the endpoint analysis. The registry also does not report sensitivity analyses evaluating alternative assumptions about missing outcomes.
The use of the term intent-to-treat in the population description should be read with its stated eligibility conditions. The record's definition excludes randomized patients without a dose or without an efficacy assessment from that described analysis population. Whether and how those patients were included in other analyses is not reported in the registry record.
These omissions do not demonstrate that the trial lacked a multiplicity plan or missing-data procedures; they mean that those details are not reported in the registry record. Consequently, the posted estimates can be described, but the robustness of the full set of statistical conclusions cannot be assessed from the registry information alone.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Tocilizumab 8 mg/kg | 19 | 162 | 11.7% |
| Adalimumab 40 mg | 16 | 162 | 9.9% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tocilizumab 8 mg/kg | 66 of 162 |
| Adalimumab 40 mg | 65 of 162 |
Most frequent serious adverse event terms
| Event term | Organ system | Tocilizumab 8 mg/kg | Adalimumab 40 mg |
|---|---|---|---|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 3 of 162 | 1 of 162 |
| Myocardial infarction | Cardiac disorders | 1 of 162 | 2 of 162 |
| Cellulitis | Infections and infestations | 0 of 162 | 2 of 162 |
| Atrial fibrillation | Cardiac disorders | 1 of 162 | 1 of 162 |
| Appendicitis perforated | Infections and infestations | 1 of 162 | 0 of 162 |
| Bronchitis | Infections and infestations | 1 of 162 | 0 of 162 |
| Haematoma infection | Infections and infestations | 1 of 162 | 0 of 162 |
| Infective tenosynovitis | Infections and infestations | 1 of 162 | 0 of 162 |
| Parotitis | Infections and infestations | 0 of 162 | 1 of 162 |
| Postoperative abscess | Infections and infestations | 1 of 162 | 0 of 162 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tocilizumab 8 mg/kg | Adalimumab 40 mg |
|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | 18 of 162 | 17 of 162 |
| Nasopharyngitis | Infections and infestations | 17 of 162 | 13 of 162 |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 9 of 162 | 15 of 162 |
| Urinary tract infection | Infections and infestations | 9 of 162 | 11 of 162 |
| Hypertension | Vascular disorders | 13 of 162 | 7 of 162 |
| Headache | Nervous system disorders | 9 of 162 | 9 of 162 |
| Nausea | Gastrointestinal disorders | 6 of 162 | 10 of 162 |
| Cough | Respiratory, thoracic and mediastinal disorders | 4 of 162 | 9 of 162 |
Serious events with the highest arm-level rate: rheumatoid arthritis (1.9%), cellulitis (1.2%), myocardial infarction (1.2%), appendicitis perforated (0.6%), bronchitis (0.6%).
The registry reports serious adverse events affecting 19 patients in the tocilizumab group and 16 in the adalimumab group. The serious-event risk set is 162 in each group. Other adverse events affected 66 patients in the tocilizumab group and 65 in the adalimumab group, with a risk set of 162 in each group. These are counts of affected patients, not measures of event severity beyond the serious-event classification, and they do not by themselves establish whether one regimen has a different safety profile.
The record lists serious adverse event terms and percentages, including rheumatoid arthritis, cellulitis, myocardial infarction, appendicitis perforated, bronchitis, and haematoma infection. The listed terms are not assigned to treatment groups in the information available in the registry record, so they should not be attributed to a particular arm. Death counts are not reported in the registry record.
Safety counts require context: the record gives the number at risk, but the figures do not describe event timing, duration, recurrence, relatedness to treatment, or statistical comparisons. Nor do they summarize every possible adverse outcome. The figures are a descriptive account of recorded affected patients and should be interpreted separately from the efficacy estimates.
12. What the Result Does, and Does Not, Mean
The posted primary estimates describe mean change in DAS28 over the period from baseline to Week 24. Both group means are negative, which the registry defines as improvement. The tocilizumab arm's posted mean change is more negative than the adalimumab arm's. This is a descriptive comparison of the reported arm estimates; the registry does not report a direct adjusted between-group estimate or its confidence interval for the primary outcome.
The record also reports higher response proportions in the tocilizumab group for the posted remission, low disease activity, and EULAR good response outcomes. Those observations add context to the average score changes, but are not substitutes for the missing primary comparative analysis. Their unadjusted comparisons should be treated as exploratory because the registry does not report how multiplicity was handled.
These data do not show how every individual responded. A group mean can conceal substantial variation, and a response threshold reduces a continuous score to a yes-or-no classification. The confidence intervals characterize uncertainty in group means, not the range of individual outcomes or certainty about what will happen to a future patient.
The registry result also does not establish that the finding applies to people outside the described population, to different treatment schedules, or to other durations of follow-up. Treatment was anticipated to last 24 weeks, and the primary endpoint is assessed at Week 24. The record does not provide longer-term outcome estimates in the information summarized for these results.
Finally, statistical estimates do not alone determine clinical importance. The registry does not report a threshold for a clinically meaningful difference in DAS28 change or a complete comparative analysis for the primary endpoint. The posted results can be read as evidence about measured outcomes in this trial, with uncertainty and reporting limitations, rather than as a universal conclusion about treatment choice.
13. Why This Trial Matters Statistically
This trial is statistically informative because it compares active monotherapy regimens in a randomized parallel-group design and uses a continuous disease activity measure as its primary outcome. The outcome combines several components of rheumatoid arthritis activity, and the registry specifies how change is interpreted. Reporting group means with confidence intervals gives readers a view of the estimated average change and its precision within each arm.
The trial also illustrates why a descriptive difference in arm summaries is not the same as the primary comparative estimate. Randomization makes the between-group contrast central to inference, while arm-specific change can also reflect common time effects and other influences. Because the registry does not report the direct primary contrast, the most important inferential quantity remains unavailable in the registry record.
The secondary endpoints show how conclusions may depend on outcome definition. Continuous change, remission thresholds, low disease activity, and response classifications summarize different features of the same clinical course. Related secondary measures can reinforce a descriptive pattern, but their correlation and the absence of a reported multiplicity strategy make them less suitable as independent confirmation.
The record is also a useful reminder that transparency about analysis populations, missing data, and planned testing matters. The population definition is stated, but details about missing outcomes, model specifications, and sponsor-reported comparative analyses are not reported in the registry record. Those omissions constrain reproducibility and the strength of conclusions that can be drawn from posted summaries alone.
Finally, the sample-size scenarios are planning illustrations based on observed effects, not evidence of the trial's design assumptions or observed power. Keeping planning calculations separate from trial results prevents a common statistical misinterpretation and helps readers evaluate what the record does—and does not—establish.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpretation is that the registry provides arm-specific primary means and confidence intervals but not a direct between-group estimate, confidence interval, or comparative P value. Since the trial question is comparative, the missing contrast restricts assessment of the magnitude and precision of the primary treatment comparison. Subtracting the arm means would not recover the adjusted estimate described by the registry.
The primary population is described as an intent-to-treat population, but it is restricted to randomized patients who received at least 1 dose and had at least 1 efficacy assessment. The registry does not explain how randomized patients outside that definition were handled, nor how missing Week 24 assessments were addressed. Model details beyond adjustment for duration of rheumatoid arthritis and region are not reported in the registry record.
There are also limits to interpretation of secondary outcomes. The registry lists several outcome domains, but the posted secondary results summarized in the record cover only some of them. A multiplicity plan and sponsor-reported comparative analyses are not reported. The unadjusted recalculated comparisons therefore should not be treated as confirmatory evidence across the full collection of outcomes.
The population is specific to patients with rheumatoid arthritis for whom methotrexate was not tolerated or continued use was considered inappropriate. Generalizing beyond that population, the studied treatment schedules, or the Week 24 assessment requires evidence not included in these results. Safety information is also limited to the reported affected-patient counts and listed serious-event terms; event timing, treatment relatedness, and group assignment for the listed terms are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Tocilizumab (RoActemra/Actemra) Versus Adalimumab in Patients With Rheumatoid Arthritis — NCT01119859.
- Registry record last updated 2013-02-11; status last verified 2013-01.
- Results first posted 2013-02-11.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a completed, randomized, double-blind, parallel-group Phase 4 trial of tocilizumab versus adalimumab as monotherapy in patients with rheumatoid arthritis who were intolerant of methotrexate or for whom continued methotrexate was considered inappropriate. Treatment was anticipated to last 24 weeks, with matching placebo administrations used for the different routes and schedules.
The primary outcome was mean change from baseline to Week 24 in DAS28. The posted mean changes were -3.3 for tocilizumab and -1.8 for adalimumab, with 95% confidence intervals of -3.57 to -3.02 and -2.1 to -1.55, respectively. A direct primary between-group estimate is not reported in the registry record. Posted secondary results include remission, low disease activity, and EULAR good response; their unadjusted comparisons do not account for a reported multiplicity plan.
The record reports serious and other adverse event counts by treatment group. Important details about missing data, the full statistical analysis, and sponsor-reported comparative analyses are not reported in the registry record.