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 on Safety and Efficacy of Tocilizumab (RoActemra/Actemra) Alone or in Combination With Non-Biologic Antirheumatics in Participants With Rheumatoid Arthritis (NCT01987479), a na phase 3 study. The primary outcome is Percentage of Participants With Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01987479 |
| Phase | Phase 3 |
| Condition | Rheumatoid Arthritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 150 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled participants with rheumatoid arthritis who had an inadequate response to non-biologic disease-modifying antirheumatic drugs. The registry identifies the primary analysis population as the FAS population. It does not report further eligibility details or a description of how the FAS population was defined.
Intervention
Participants received subcutaneous tocilizumab, either alone or alongside methotrexate or other non-biologic DMARDs. The recorded regimen was a weekly injection of 162 milligrams for 24 weeks. The study was open-label, so treatment masking was not used.
Comparator
There was no separate control group. The registry describes the study as single-group and lists allocation as not applicable. Participants could receive tocilizumab alone or in combination with background drugs, but those treatment choices do not create a randomized comparison. Any contrast between those approaches would require details and analyses not reported in the registry record.
Primary question
The primary endpoint asks what percentage of participants experienced an adverse event from baseline up to Week 32. The record defines an adverse event as an untoward medical occurrence in someone who received study drug, regardless of whether a causal relationship was considered possible. Serious and non-serious adverse events are included. The posted safety figures distinguish participants with serious events from those with other events, but do not report an inferential comparison or a treatment effect relative to a control group. The listed secondary outcomes concern measures of rheumatoid arthritis activity and response, but their results are not reported in the registry record.
3. Trial Design
This was a multicenter, open-label, single-arm Phase IIIb study of subcutaneous tocilizumab in participants with rheumatoid arthritis and an inadequate response to non-biologic DMARDs. The registry lists the study as Phase 3. It was sponsored by Hoffmann-La Roche and is recorded as completed. The recorded start date is 2014-01-30, and the primary completion date is 2016-05-26.
The planned enrollment was 150. Participants received tocilizumab alone or in combination with methotrexate or another non-biologic DMARD. The regimen was a weekly subcutaneous injection of 162 milligrams for 24 weeks. The registry does not describe a randomized assignment process, and allocation is listed as not applicable. There was no masking. Consequently, the study design does not support a randomized comparison between tocilizumab and a separate control treatment.
The primary outcome was the percentage of participants with adverse events, assessed from baseline up to Week 32. The definition includes serious and non-serious events and does not require investigators to judge an event as caused by study treatment. The primary population is identified as the FAS population, but the registry record does not define that population further.
Secondary outcomes listed in the registry include changes in DAS28-ESR, SDAI and CDAI, as well as ACR20, ACR50, ACR70 and ACR90 response and EULAR response. The listed assessment times include multiple visits, with the final scheduled visit at Week 24 for several measures and early withdrawal for some change-from-baseline outcomes. Results for these efficacy outcomes are not reported in the registry record. The record also does not report the protocol’s sample-size justification, detailed statistical analysis plan, or the handling of treatment discontinuation.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: A total of 174 participants were screened, out of which 150 participants met eligibility criteria and were enrolled into the study.
Overall Study
| Stage | Tocilizumab Alone or in Combination With Methotrexate or DMARD |
|---|---|
| STARTED | 150 |
| COMPLETED | 133 |
| NOT COMPLETED | 17 |
Reasons for not completing this period:
| Reason | Tocilizumab Alone or in Combination With Methotrexate or DMARD |
|---|---|
| Protocol Violation | 1 |
| Physician Decision | 2 |
| Participant/legal guardian decision | 1 |
| Other | 5 |
| Lost to Follow-up | 1 |
| Adverse Event | 7 |
Analysis population for the primary outcome, as defined in the registry: FAS population
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: Full Analysis Set (FAS) population included all participants who received at least one dose of SC tocilizumab.
| Characteristic | Unit | Tocilizumab Alone or in Combination With Methotrexate or DMARD |
|---|---|---|
| Participants analysed | 150 | |
| Age, Continuous | years | 55.85 (SD 11.20) |
| Sex: Female, Male: Female | Participants | 110 |
| Sex: Female, Male: Male | Participants | 40 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Adverse Events, measured over Baseline up to Week 32.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with adverse events from baseline up to Week 32. An adverse event is defined broadly as an untoward medical occurrence in a participant who received study drug, regardless of whether a causal link to treatment is considered possible. The definition includes both serious and non-serious events.
Adverse-event monitoring is used to describe the safety experience observed during treatment and follow-up. A broad definition can capture medical occurrences without requiring investigators to settle whether treatment caused them. That makes the measure a record of events occurring in the observed treatment group, not by itself a measure of events attributable to treatment.
The endpoint is expressed as a percentage of participants, while the posted safety data also give participant counts and denominators for serious and other adverse events. These summaries describe how many participants were recorded in each category within the study group. They do not establish what would have happened under a different treatment, because the study had no separate control group. Nor do the counts alone describe event timing, duration, recurrence, or severity beyond the serious-event classification. Those details are not reported in the registry record.
The timeframe extends to Week 32, whereas the treatment regimen is described as lasting 24 weeks. These are distinct recorded timeframes: the endpoint includes a safety observation period stated as baseline up to Week 32, and the dosing schedule is stated as 24 weeks. The registry does not provide additional detail about the follow-up procedures within that period.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results describe events among participants treated with tocilizumab alone or with methotrexate or another non-biologic DMARD. The registry reports 14 participants with serious adverse events and 77 participants with other adverse events, each among 150 at risk. These are descriptive counts from a single-group study. They are not a comparison against an untreated group or a different treatment group.
The categories should not be combined to create a total number of participants with any adverse event. The record does not say that the serious and other-event categories are mutually exclusive, and participants could be represented in more than one event category. No total has therefore been inferred. The primary endpoint is defined as the percentage with adverse events overall, but the posted safety information does not give a single overall percentage for that endpoint. No percentage has been calculated from the participant counts.
The record lists appendicitis, bacterial arthritis, skin infection, scapula fracture, tibia fracture and arthralgia among the top serious terms, each recorded as 0.7%. These are event terms in the safety summary. The registry does not report a causal assessment for each term, and the broad adverse-event definition explicitly does not require a possible causal relationship to study drug. The terms should therefore be read as reported events, not as findings that tocilizumab caused them.
The study was open-label, which means treatment masking was absent. It also had no separate control group. These design features matter when interpreting reports of adverse events: the summaries characterize what was recorded in this study, but they do not isolate treatment effects from underlying illness, background therapy, or other influences. The registry does not report a controlled estimate, confidence interval, hypothesis test, or adjusted safety comparison.
The registry lists several disease-activity and response outcomes as secondary endpoints, including DAS28-ESR, SDAI, CDAI, ACR responses and EULAR response. Their results are not reported in the registry record. The available safety summaries therefore do not establish the study’s observed efficacy results. They also do not permit a quantitative comparison of safety or efficacy between monotherapy and combination therapy.
In statistical terms, the posted figures have a descriptive scope. They indicate the reported participant counts in the safety categories and list selected serious-event terms. A descriptive count does not convey precision in the form of a confidence interval, and no such interval is reported. The record also does not provide further information about missing safety observations, event ascertainment, or the statistical methods used. Interpretation should remain within the limits of these reported summaries.
9. Statistical Methods Explained
Statistical methods determine how observations are summarized and what comparisons can be supported. For this study, the design information identifies an open-label, single-group trial with allocation listed as not applicable. That design sets an important boundary: the safety summaries describe participants in the study, but they do not provide a randomized estimate of how outcomes differ from those under another treatment.
What does a participant percentage represent?
A participant percentage expresses the share of a defined analysis group that experienced an outcome during a specified period. It is different from an event count when one participant can experience more than one event. The primary outcome is stated as the percentage of participants with adverse events from baseline up to Week 32. The record also presents counts for participants with serious and other adverse events, with 150 at risk in each category. No overall percentage for the primary endpoint is stated in the posted results, and none is recalculated.
Counts and percentages depend on a defined denominator. The primary population is identified as the FAS population, while the adverse-event summaries use the at-risk group shown for each category. The registry does not explain whether those populations have identical inclusion rules or provide a detailed definition of FAS. Reading a percentage requires knowing who is included in its denominator and how participants with incomplete follow-up are handled. Those methods are not reported in the registry record.
What does an adverse-event summary establish?
An adverse-event summary records occurrences under a stated definition and observation period. Here, the definition covers untoward medical occurrences in people who received study drug, whether or not a causal relationship is considered possible. That broad approach helps describe events observed during treatment and follow-up, but occurrence alone does not establish causation. A comparison group, defined causal assessment procedures, and other design details can inform causal interpretation; a single-group count cannot supply a treatment contrast on its own.
Seriousness and event type are also separate dimensions. The record reports a serious-event count and selected serious-event terms. A term such as a fracture or infection identifies the type of event listed; the seriousness classification indicates a separate reporting category. The registry does not provide enough detail to infer the clinical course, recurrence, duration, or individual-level overlap among those terms.
Why does the single-group design matter?
Randomization, when used, can help make treatment groups comparable in expectation, while masking can reduce some influences on treatment delivery and outcome assessment. Neither feature is present as a randomized, masked comparison in this record: the study is single-group and open-label. As a result, differences between treatment choices within the group, if someone were to calculate them, could reflect participant or treatment-selection differences rather than treatment effects. The record does not report a planned or adjusted comparison between monotherapy and combination therapy.
General statistical principle: confidence intervals describe the uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. The registry does not report a confidence interval for the primary safety endpoint. A point count without an interval does not communicate the full sampling uncertainty, and no precision estimate should be inferred from the counts alone.
What can a hypothesis test tell a reader?
General statistical principle: a hypothesis test assesses how compatible observed data are with a specified null model, given the test’s assumptions. A p-value does not give the probability that a treatment works, nor does it by itself show clinical importance. In a single-group safety summary, a test against a reference value would require a specified reference and analysis plan. Neither a test result nor such a comparison is reported in the registry record. The record also does not report p-values for the listed efficacy outcomes.
Adjusted estimates can account for measured covariates under a defined model, but adjustment cannot automatically remove unmeasured differences or create a randomized control group. No adjusted analysis is reported. The record also does not report model specifications, covariates, assumptions, or diagnostic checks. Accordingly, interpretation should not imply a model-based causal estimate.
How should multiple outcomes be understood?
The registry lists multiple secondary measures and assessment times. General statistical principle: when many outcomes or repeated assessments are examined, the chance of observing an apparently unusual result somewhere among them can increase. A prespecified analysis plan may address this through a hierarchy of endpoints, adjusted testing, or an explicitly exploratory interpretation. The registry record does not report how multiplicity was handled, whether any outcomes were designated for formal hypothesis testing, or whether analyses were planned at each listed time. No claim about statistical significance across those outcomes is possible from the information reported.
The record gives a primary endpoint timeframe of baseline up to Week 32 and describes dosing for 24 weeks. These time references should not be conflated. The endpoint’s observation window and the treatment schedule describe different aspects of the study. The registry does not provide more detail about timing of individual adverse events or the statistical approach to follow-up.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Tocilizumab Alone or in Combination With Methotrex | 150 | 137 | 91.3% | 85.6% to 95.3% | 85.7% to 94.9% | 85.7% to 94.8% |
R code and output
arm <- c("Tocilizumab Alone or in Combination With Methotrex")
n <- c(150)
events <- c(137)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Tocilizumab Alone or in Combination With Methotrex 150 137 91.3 85.6 95.3 85.7 94.9 85.7 94.811. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety outcome and multiple secondary outcomes, including several disease-activity measures, response categories and assessment times. When many outcomes or time points are evaluated, general statistical reasoning recognizes that isolated findings can occur by chance. A prespecified hierarchy, multiplicity adjustment, or exploratory interpretation can help clarify how such results should be understood. The method used in this study is not reported in the registry record. No efficacy results or testing details are reported, so no conclusion about multiplicity-adjusted evidence can be drawn.
Missing-data methods are also not reported in the registry record. The listed primary analysis population is the FAS population, but the record does not define its membership, explain how participants who discontinued treatment were handled, describe the availability of outcome measurements, or state how missing observations were addressed. For repeated disease-activity assessments, those details can affect the number of observations contributing at each time and the interpretation of change over time. They should not be guessed.
The safety summary gives 150 at risk for the serious-event category and 150 at risk for other adverse events. It does not describe completeness of follow-up, whether all participants were observed through Week 32, or how event reports were collected after treatment ended. The registry also does not report imputation, censoring, sensitivity analyses, or other missing-data procedures. Thus, the posted counts can be described as recorded summaries, but their relationship to incomplete observation cannot be assessed from the registry record.
12. 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 Alone or in Combination With Methotrexate or DMARD | 14 | 150 | 9.3% |
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 Alone or in Combination With Methotrexate or DMARD | 77 of 150 |
Most frequent serious adverse event terms
| Event term | Organ system | Tocilizumab Alone or in Combination With Methotrexate or DMARD |
|---|---|---|
| Appendicitis | Infections and infestations | 1 of 150 |
| Arthritis bacterial | Infections and infestations | 1 of 150 |
| Skin infection | Infections and infestations | 1 of 150 |
| Scapula fracture | Injury, poisoning and procedural complications | 1 of 150 |
| Tibia fracture | Injury, poisoning and procedural complications | 1 of 150 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1 of 150 |
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | 1 of 150 |
| B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 150 |
| Bowen's disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 150 |
| Psoriasis | Skin and subcutaneous tissue disorders | 1 of 150 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tocilizumab Alone or in Combination With Methotrexate or DMARD |
|---|---|---|
| Nasopharyngitis | Infections and infestations | 35 of 150 |
| Nausea | Gastrointestinal disorders | 18 of 150 |
| Fatigue | General disorders | 18 of 150 |
| Dizziness | Nervous system disorders | 11 of 150 |
| Diarrhoea | Gastrointestinal disorders | 9 of 150 |
| Rash | Skin and subcutaneous tissue disorders | 8 of 150 |
| Leukopenia | Blood and lymphatic system disorders | 8 of 150 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 8 of 150 |
Serious events with the highest arm-level rate: appendicitis (0.7%), arthritis bacterial (0.7%), skin infection (0.7%), scapula fracture (0.7%), tibia fracture (0.7%).
The registry reports 14 participants with serious adverse events and 77 participants with other adverse events, with 150 at risk in each category. These are participant counts. The record lists appendicitis, bacterial arthritis, skin infection, scapula fracture, tibia fracture and arthralgia among the top serious terms, each at 0.7%.
The serious and other-event counts should not be added to produce a total number of participants with an adverse event. The registry does not report whether the categories overlap at participant level. The top serious terms are also not a complete event history: the record does not provide event timing, recurrence, duration, or participant-level links among terms. Deaths are not reported in the registry record.
The endpoint definition includes events regardless of whether a causal relationship to treatment is considered possible. Therefore, these figures describe events recorded in the study rather than proving that treatment caused them. As the study had no separate control group, the summaries do not quantify how the observed event experience compares with another treatment or with no study treatment. No confidence interval or comparative safety estimate is reported.
13. What the Result Does, and Does Not, Mean
The result supports a descriptive statement about safety reporting in this study: the registry records 14 participants with serious adverse events and 77 with other adverse events, each among 150 at risk. It also lists selected serious-event terms, each recorded at 0.7%. These observations describe the treated study group during the recorded safety period. They do not, on their own, establish a causal effect of tocilizumab.
The study included tocilizumab as monotherapy or in combination with methotrexate or another non-biologic DMARD. Because it was single-group and open-label, the record does not offer a randomized comparison with a control treatment. It also does not report a treatment-effect estimate comparing monotherapy with combination therapy. The event summaries cannot establish whether one regimen has a different safety profile from another.
The primary endpoint concerns adverse events, not improvement in rheumatoid arthritis activity. Although the registry lists secondary outcomes for disease activity and response, their results are not reported in the registry record. It is therefore not possible to characterize the observed efficacy outcomes from the information reported. Nor can the safety counts be used as a substitute for those outcomes.
The figures also do not establish how precisely the underlying event experience has been estimated. No confidence interval, hypothesis test, or adjusted analysis for the primary outcome is reported. The registry does not explain missing-data handling or provide detailed follow-up completeness information. These omissions limit assessment of uncertainty and the possible effect of incomplete observation.
The appropriate scope of interpretation is consequently narrow: the record describes reported adverse-event counts and selected serious-event terms in a single-group study with a stated treatment regimen and observation window. It does not show comparative risk, prove causation, provide an efficacy result, or determine what would occur in a different population or treatment setting. Those questions require evidence and analyses not reported in the registry record.
14. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between safety description and comparative treatment evidence. A single-group registry summary can report which events were recorded among participants receiving a regimen. It cannot by itself show how those outcomes compare with what would have occurred under an alternative treatment. The open-label design and absence of a separate control group make that distinction especially important when interpreting adverse-event counts.
The endpoint definition is also consequential. It includes untoward medical occurrences regardless of whether a causal relationship is considered possible. That captures a broad safety experience, but it means the reported events should not automatically be attributed to treatment. Seriousness, event type, and causal attribution answer different questions and should not be treated as interchangeable.
The record illustrates why a denominator and a clearly defined analysis population matter. It identifies the FAS population for the primary endpoint and reports 150 at risk for each of the serious and other-event summaries, but it does not provide a full account of how analysis populations were defined or how missing observations were handled. Those methodological details help readers judge what the summaries represent and how complete the observation may be.
Finally, the registry lists a broad set of secondary measures and assessment times, but does not report their results or a multiplicity strategy. A list of outcomes establishes what was planned or registered, not what was observed or statistically supported. Separating registered questions from posted findings helps prevent an endpoint list from being mistaken for evidence of efficacy. This record therefore offers a useful case for reading safety summaries within the limits set by design, reporting, and analysis information.
15. 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 design is single-group, open-label, and has no separate control group. As a result, the reported safety counts are descriptive and cannot estimate a randomized contrast against another treatment. The record also does not report a planned comparison between tocilizumab alone and tocilizumab in combination with methotrexate or another non-biologic DMARD. The treatment options within the study should not be treated as equivalent to randomized arms.
The primary endpoint is defined as the percentage of participants with adverse events, but the posted safety information gives counts for serious and other events rather than a single overall percentage. The record does not indicate whether those categories overlap, so a total participant count cannot be derived from them. Selected serious-event terms are listed, but detailed event-level information such as timing, duration, recurrence, and participant-level overlap is not reported.
The primary population is identified as FAS, without a further definition in the registry record. Missing-data procedures, completeness of follow-up, treatment discontinuation handling, and sensitivity analyses are not reported. These omissions limit assessment of how the analysis population was formed and how incomplete observations might affect the summaries.
Results for the listed secondary efficacy outcomes are not reported in the registry record. Nor are confidence intervals, hypothesis tests, adjusted estimates, multiplicity procedures, or a detailed statistical analysis plan. The figures therefore do not permit assessment of efficacy, comparative safety, or statistical precision. The reported event definition does not require causal attribution, which further limits claims about whether study treatment caused any listed event.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study on Safety and Efficacy of Tocilizumab (RoActemra/Actemra) Alone or in Combination With Non-Biologic Antirheumatics in Participants With Rheumatoid Arthritis — NCT01987479.
- Registry record last updated 2017-06-19; status last verified 2017-05.
- Results first posted 2017-06-19.
- 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.
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19. Record Summary
The registry describes a completed, multicenter, open-label, single-group Phase IIIb study of subcutaneous tocilizumab in participants with rheumatoid arthritis and an inadequate response to non-biologic DMARDs. Participants received weekly tocilizumab, alone or with methotrexate or another non-biologic DMARD, for 24 weeks. Planned enrollment was 150.
The primary endpoint was the percentage of participants with adverse events from baseline up to Week 32. The posted safety summaries report 14 participants with serious adverse events and 77 with other adverse events, each among 150 at risk. Selected serious-event terms are listed at 0.7% each. The study has no separate control group, and treatment masking was not used.
Secondary disease-activity and response outcomes are listed, but their results are not reported in the registry record. Detailed statistical methods, multiplicity handling, and missing-data procedures are also not reported. The available evidence is therefore descriptive safety information, not a comparative treatment-effect estimate.