A follow-on Safety Study in Subjects With Crohn's Disease Who Have Previously Been Withdrawn From the Double-blind Study CDP870-031 [NCT00152490] or CDP870-032 [NCT00152425] Due to an Exacerbation of Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A follow-on Safety Study in Subjects With Crohn's Disease Who Have Previously Been Withdrawn From the Double-blind Study CDP870-031 [NCT00152490] or CDP870-032 [NCT00152425] Due to an Exacerbation of Crohn's Disease (NCT00160706), a na phase 3 study. The primary outcome is Percentage of Subjects With at Least One Adverse Event (AE) During the Duration of This Study CDP870-034 (up to 84 Months).

2. Clinical Question

The registry record describes a safety question in a selected follow-on population, rather than a randomized test of treatment against another intervention or placebo. Participants had a history of Crohn’s disease exacerbation serious enough to lead to withdrawal from one of the feeder studies. That history is important context: the results concern people entering this specific follow-on study, not an unrestricted population with Crohn’s disease.

The primary outcome is an occurrence measure: whether a subject had at least one adverse event over the specified observation period. It does not by itself describe the event’s severity, duration, recurrence, or likely cause. The registry also lists serious adverse events and other adverse events separately, along with serious-event terms. Those safety summaries add context but do not create a controlled comparison.

The registry record does not report an untreated or active-comparator group. Consequently, the central question is descriptive—what adverse events were recorded in this cohort during follow-up—not whether the intervention caused more or fewer events than an alternative would have caused.

3. Trial Design

This was a Phase III, multinational, multicentre, open-label, single-group safety study sponsored by UCB Pharma SA. The registry lists the study as completed, with enrollment of 310. Its stated purpose was to assess safety after re-exposure to certolizumab pegol following a variable interval and during subsequent chronic therapy in people with active Crohn’s disease who had previously been withdrawn from CDP870-031 or CDP870-032 because of disease exacerbation.

The treatment regimen began with certolizumab pegol 400 mg at Weeks 0, 2 and 4, followed by 400 mg every 4 weeks. The regimen description says treatment continued until Week 360. The primary outcome timeframe is described as up to 84 months, from Study Entry at Week 0 to the Study End at Week 362, with a Safety Follow-up at Week 372. These are the registry’s stated schedule descriptions; they should not be treated as interchangeable measures of each individual’s actual time under observation.

Open-label means that masking was not used, as also recorded in the registry. The allocation field is not applicable, and the study model is single-group. There is therefore no randomized parallel control group in the record against which to compare adverse-event frequency. The design can describe events recorded during follow-up, but it cannot isolate the intervention’s effect from the underlying disease, participant characteristics, prior treatment, or other influences by means of a randomized contrast.

The safety population is described as all 310 subjects included in the primary outcome analysis. It comprises enrolled subjects who received at least one injection of study treatment in feeder study C87031 or C87032. The record does not describe further details of eligibility, treatment adherence, follow-up completeness, or reasons for missing assessments. The study start is listed as 2004-02 and primary completion as 2012-05.

Secondary outcomes listed include Harvey Bradshaw Index remission and response, plasma certolizumab pegol concentration, anti-CZP antibody status, C-reactive protein, and fecal calprotectin. The registry record gives those outcome descriptions but does not report their numerical results in the material available for this 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.

Before assignment: Subjects who withdrew from feeder studies for worsening of Crohn's Disease entered study C87034. Subjects in study C87031 were eligible for entry into C87034 at any time after completing the Week 2 assessment, subjects in study C87032 at any time after completing the Week 6 randomisation.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All 310 subjects in the Safety Population are included in the analysis of this outcome measure. Safety Population includes all enrolled subjects who received at least one injection of study treatment in feeder study C87031 \[NCT00152490\] or C87032 \[NCT00152425\].

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Baseline Characteristics refer to the Safety Population, including all enrolled subjects who received at least one injection of study treatment in feeder study C87031 \[NCT00152490\] or C87032 \[NCT00152425\].

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects With at Least One Adverse Event (AE) During the Duration of This Study CDP870-034 (up to 84 Months), measured over Up to 84 months from Study Entry (Week 0) to the Study End (Week 362 ) and the Safety Follow-up (Week 372).

The primary outcome is the percentage of subjects with at least one adverse event during the duration of study CDP870-034, described as up to 84 months. The registry defines an adverse event as an untoward medical occurrence in a subject or clinical investigation subject given a pharmaceutical product; the occurrence does not necessarily have a causal relationship with that treatment.

An any-event measure is used in safety reporting to capture whether participants experienced one or more events during observation. It is broad: a subject is counted as having an event if at least one qualifying event is recorded, regardless of whether the event is mild or serious, related or unrelated, or a single occurrence or one of several. The measure is useful for describing the overall burden of reported events, but it does not communicate those distinctions by itself.

The primary outcome description identifies 310 subjects in the safety population. The posted safety summary separately lists 248 subjects affected by other adverse events and 138 affected by serious adverse events. Those categories are not presented as mutually exclusive, so their counts should not be added. The registry record does not give a primary-outcome percentage or a confidence interval in the information available for this interpretation.

Because this was a single-group, open-label study, the endpoint describes events observed during follow-up in this cohort. It does not estimate how event occurrence would differ under a control treatment or no study treatment. Nor does the primary outcome alone establish that a reported event was caused by certolizumab pegol.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is binary at the subject level: a subject either had at least one adverse event during the specified period or did not. The registry describes the primary result as a percentage of subjects. This kind of summary is straightforward to interpret as a proportion of the defined safety population, but its meaning depends on the event definition, observation period, and analysis population. The event definition includes occurrences that are not necessarily considered caused by treatment.

What a proportion describes

In general, a proportion expresses the number of people meeting a stated condition relative to the number assessed for that condition. For a safety endpoint, the condition is having at least one qualifying event. A person with multiple events still meets that subject-level condition; the proportion does not count the total number of event episodes. The registry lists 310 as the safety population for the primary outcome. Its safety summary separately reports 248 subjects affected by other adverse events and 138 affected by serious adverse events. The record excerpt does not provide the primary outcome percentage itself.

A percentage is a compact description, not a complete account of uncertainty or event burden. A confidence interval, when reported, describes the statistical uncertainty around an estimate under the assumptions of the method used. It does not correct for selection into the study, differences in follow-up, outcome misclassification, or lack of a comparator. No confidence interval for the primary endpoint is reported in the registry record information considered.

Why the single-group design matters

General statistical principle: a treatment effect is a contrast between outcomes under different treatment conditions. Randomized groups can make such a contrast more interpretable by balancing, on average, measured and unmeasured baseline factors. This study is listed as single-group, with allocation not applicable and masking none. It therefore supplies no randomized treatment contrast. Comparing its adverse-event proportion with an external group or a different study would require additional assumptions about comparability that are not established by this record.

The study’s follow-on setting also defines who the findings describe. Participants had previously been withdrawn from feeder studies after Crohn’s disease exacerbation. Results from this selected group should not automatically be generalized to people with different disease histories or to other treatment settings. This is a question of the population to which an estimate applies, not a calculation that can be resolved by a larger denominator alone.

Event categories and overlap

The registry lists serious adverse events and other adverse events as separate safety-summary categories. Without a statement that the categories are mutually exclusive, a subject could be represented in both. Adding the affected-subject counts would risk double counting. In general, event counts, numbers of affected subjects, and percentages of subjects are different quantities: one subject may have more than one event, while an any-event endpoint counts that subject once.

The serious-event terms are also descriptive classifications. A term’s reported percentage does not establish that the intervention caused the event. Causal attribution requires a separate assessment and, for comparative causal conclusions, a design that supports a suitable counterfactual. The record excerpt does not report the attribution method or a comparator-based analysis.

Time and follow-up

The primary timeframe is described as up to 84 months, while the study schedule identifies Week 362 as the Study End and Week 372 as Safety Follow-up. The regimen description extends treatment until Week 360. These statements describe different elements of the protocol schedule; they do not show that each participant completed the same duration of treatment or follow-up. The registry record does not report individual exposure times, person-time, or time-to-event estimates in the information considered.

General statistical principle: if observation time differs substantially between participants, a simple proportion over the whole study period can obscure differences in time at risk. An event rate using person-time or a time-to-event analysis may address a different question, but it requires suitable follow-up information and assumptions. The record excerpt does not provide such results, so the listed affected-subject counts should be read as counts rather than time-adjusted rates.

Multiplicity and other outcomes

The registry lists secondary outcomes covering clinical indices, drug concentration, antibody status, inflammatory markers, and fecal calprotectin. When multiple outcomes are assessed, the chance of at least one apparently notable result can increase if each is tested separately. General statistical practice may address that issue through a prespecified testing hierarchy or multiplicity adjustment. The registry record does not report a multiplicity strategy, the complete analysis plan, or inferential results for the listed secondary outcomes. It is therefore not possible to determine how those outcomes were prioritized or how any multiple-testing issue was handled.

The record lists zero analyses. That means no analysis entries are reported in the registry information considered; it does not establish that no analyses were conducted outside the registry record. The statistical plan, missing-data procedures, interim analyses, and sample-size justification are not reported in the registry record.

The sample-size assumptions described for planning illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects expressed as fractions of an observed effect. Those are planning assumptions, not a description of this single-group study’s own design. Any such sample-size illustration is not observed power and cannot supply evidence that a treatment effect was present. The registry does not report the original sample-size justification.

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.

R code and output

arm    <- c("Certolizumab Pegol")
n      <- c(310)
events <- c(292)
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  Certolizumab Pegol  310  292  94.2  91.0  96.5  91.0  96.3  91.0  96.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and several secondary outcomes, including clinical response and remission measures, plasma concentration, antibody status, C-reactive protein, and fecal calprotectin. It does not report a hierarchy for testing these outcomes, a multiplicity adjustment, or a complete statistical analysis plan. Without that information, the intended control of false-positive findings across multiple analyses is not reported in the registry record.

The record lists zero analyses. This describes the registry entry, not necessarily the full work conducted by the sponsor or investigators. No interim-analysis plan or interim results are reported in the registry record. The sample-size justification is also not reported in the registry record, so the enrollment figure should not be taken as evidence of a particular precision target or power calculation.

The primary outcome description states that the safety population includes all 310 enrolled subjects who received at least one injection of study treatment in a feeder study. The registry excerpt does not report how missing outcome information was handled, whether any subjects were excluded from a particular analysis, or how incomplete follow-up was addressed. It also does not provide the number with missing primary-outcome status or a sensitivity analysis for missing data. A complete-case or other specific approach should not be assumed.

In general, missing-data handling matters when the chance that an observation is unavailable is related to health status or adverse events. If participants with less complete follow-up differ from those observed throughout, a simple observed proportion may not represent the same population as a fully observed outcome. That is a general methodological concern; the registry record does not report enough detail to assess its impact in this study.

The serious and other adverse-event counts are presented as separate categories, but the record does not state that they are mutually exclusive. They should therefore remain separate rather than be summed. The absence of reported analytical details limits assessment of uncertainty, completeness, and multiplicity; it does not itself establish that the results are biased.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: crohn's disease (15.8%), perianal abscess (2.9%), abdominal pain (2.6%), small intestinal obstruction (2.3%), anaemia (1.6%).

The safety summary lists 138 subjects affected by serious adverse events and 248 affected by other adverse events, with 310 at risk in each category. These are affected-subject counts, not counts of every event episode. The record does not say the categories are mutually exclusive; a subject could have both a serious event and another event. The counts should not be added.

The listed serious-event terms are Crohn’s disease at 15.8%, perianal abscess at 2.9%, abdominal pain at 2.6%, small intestinal obstruction at 2.3%, anaemia at 1.6%, and abdominal abscess at 1.3%. These are percentages as reported in the registry’s serious-event listing. The denominator and any rules for repeated events are not specified in the record excerpt, so the values should not be reinterpreted as event rates or as treatment-attributable risks.

A serious adverse event is a safety classification, but the primary outcome definition includes adverse events whether or not they are related to treatment. The record excerpt does not report causal attribution for these terms. It also does not provide a death count; deaths are not reported in the registry record. These summaries describe what was recorded in the study cohort and do not compare its safety experience with a control group.

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

The results describe adverse events recorded during a long-term follow-on study of certolizumab pegol in people with Crohn’s disease who had previously been withdrawn from feeder studies after exacerbation. The primary outcome was designed to capture whether subjects experienced at least one adverse event, with the event definition explicitly allowing occurrences not considered causally related to treatment.

The safety summary reports 138 subjects affected by serious adverse events and 248 affected by other adverse events. It also lists selected serious-event terms and their reported percentages. These figures are useful as a description of the safety experience recorded in this cohort. They do not indicate how many events each affected person experienced, establish that serious and other categories do not overlap, or show that an event was caused by the study treatment.

The study was open-label and single-group, with no randomized comparator. Thus, the results do not estimate the difference in event occurrence between certolizumab pegol and another treatment or no treatment. They also do not separate treatment effects from Crohn’s disease activity, prior care, participant characteristics, or other influences. The cohort’s prior exacerbation and withdrawal history further limits how broadly its results can be generalized.

The primary endpoint is reported as a percentage, but the registry record does not give that percentage or its uncertainty interval in the information considered. The separate safety counts should not be used to construct an unreported primary estimate. No inferential analyses are listed, and the record does not report the missing-data approach or multiplicity plan. Those omissions limit the precision with which the numerical safety findings can be evaluated.

In short, this is a descriptive account of safety observations in a defined follow-on cohort. It is not a randomized comparison, a causal estimate, or a guarantee about the experience of other people with Crohn’s disease. The registry record does not establish either benefit or harm relative to an alternative treatment.

14. Why This Trial Matters Statistically

Long-term safety studies can describe events that occur during extended exposure and follow-up, including events that may not be fully represented by shorter observation periods. This study’s stated timeframe is up to 84 months, with additional week-based study and safety-follow-up milestones. Its follow-on design makes the population and treatment history central to interpreting the reported events.

Statistically, the study illustrates the difference between describing event occurrence and estimating a comparative treatment effect. The primary question is framed as the percentage of subjects with at least one adverse event. That is an interpretable safety summary, but in a single-group design it has no randomized counterfactual. A count or proportion can characterize the cohort without showing what would have happened to similar participants under another treatment.

The distinction between affected subjects and event episodes also matters. The registry separately reports serious and other adverse-event categories and lists selected serious-event terms. Those summaries provide different views of safety, but cannot be collapsed into one total without knowing whether subjects or events overlap and how each category was defined. Careful reading preserves the meaning of each measure rather than treating every percentage as a comparable risk estimate.

The study also highlights why analysis details are important. A defined safety population is reported, but the registry record does not report the missing-data method, multiplicity strategy, or primary endpoint uncertainty interval. Those details would help readers assess completeness and precision. Their absence from the registry entry should be described as missing documentation, not filled in by assumption.

Its statistical value is therefore descriptive: it records a safety experience in a specified clinical context and makes clear that the outcome is broad and not necessarily treatment-related. The design and reporting limits are equally important parts of that interpretation.

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 principal limitation for comparative interpretation is the single-group, open-label design. With allocation listed as not applicable and no control arm, the study does not estimate a randomized difference in adverse-event occurrence. Reported events cannot be attributed to treatment on the basis of these summaries alone. The registry’s adverse-event definition itself says that a causal relationship is not required.

The study population was selected: participants had previously been withdrawn from feeder studies because of Crohn’s disease exacerbation. Findings therefore describe this follow-on cohort and may not represent people with different disease histories. The registry record does not report enough baseline detail in the information considered to assess how the cohort compares with other populations.

Observation is described as up to 84 months, with Week 362 as the Study End and Week 372 as Safety Follow-up. The record does not provide individual follow-up duration or person-time. Counts of affected subjects consequently should not be interpreted as time-adjusted event rates or as if all subjects had identical exposure.

The primary endpoint is described, but its numerical percentage and uncertainty interval are not reported in the record information considered. Separate counts are given for serious and other adverse events, but their overlap is not specified. The record also does not report the deaths count, event-attribution method, missing-data handling, multiplicity plan, interim analyses, original sample-size justification, or complete statistical analysis plan. These omissions limit evaluation of precision, completeness, and analytic choices; they do not by themselves demonstrate that the study’s findings are invalid.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A follow-on Safety Study in Subjects With Crohn's Disease Who Have Previously Been Withdrawn From the Double-blind Study CDP870-031 [NCT00152490] or CDP870-032 [NCT00152425] Due to an Exacerbation of Crohn's Disease — NCT00160706.
• Registry record last updated 2018-08-07; status last verified 2013-05.
• Results first posted 2013-07-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed Phase III, multinational, multicentre study evaluated safety in a single-group, open-label follow-on cohort with Crohn’s disease. Participants had previously been withdrawn from CDP870-031 or CDP870-032 because of disease exacerbation. The regimen was certolizumab pegol 400 mg at Weeks 0, 2 and 4, followed by 400 mg every 4 weeks until Week 360, as described in the registry.

The primary outcome was the percentage of subjects with at least one adverse event during a period described as up to 84 months. The safety population was identified as 310 subjects. The safety summary lists 138 affected by serious adverse events and 248 affected by other adverse events; the categories are not stated to be mutually exclusive. Selected serious-event terms and percentages are reported, but the primary outcome percentage and its uncertainty interval are not included in the information considered.

There was no randomized comparator. The registry record does not report a multiplicity strategy, missing-data approach, interim analysis plan, or original sample-size justification. The results are descriptive safety observations and do not establish comparative effects or causal attribution.