Brodalumab (AMG 827) in Adults With Moderate to Severe Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Brodalumab (AMG 827) in Adults With Moderate to Severe Crohn's Disease (NCT01150890), a randomized phase 2 study. The primary outcome is Percentage of Participants Who Achieved Clinical Remission at Week 6.

2. Clinical Question

The question is therefore about the Week 6 outcome in the randomized groups, not about longer-term remission or the course of Crohn’s disease beyond the reported follow-up. The registry record does not report a longer-term primary endpoint. It also does not report a planned sample-size justification or a detailed statistical analysis plan, so the posted results cannot establish what effect size the trial was designed to detect.

3. Trial Design

This was a phase 2, randomized, double-blind, parallel-group, placebo-controlled study sponsored by Amgen. The registry lists an enrollment of 130 and a status of terminated. The recorded study start was 2010-11-09, and the primary completion date was 2011-10-15. The record does not explain the reason for termination, so no conclusion about why the study ended can be drawn from these details.

Participants were assigned to placebo or one of three brodalumab dose groups. The intervention descriptions state that each group received its assigned intravenous treatment at baseline and Week 4. The placebo was also administered intravenously at those time points. The brief summary describes masking of both the participant and doctor; the design fields characterize the study as double-blind.

The primary outcome was the percentage achieving clinical remission at Week 6. Its analysis population was the full analysis set, defined in the registry as all randomized participants, with missing outcomes treated as non-response. The record also lists secondary outcomes that cover CDAI response and change in CDAI at Week 6, treatment-emergent adverse events, and brodalumab concentration and pharmacokinetic measures.

Although the design and treatment schedule are described, the registry record does not report the planned sample-size justification, the full allocation procedure, or details such as any stratification factors. The statistical analysis plan, including whether interim analyses were intended, is not reported in the registry record. These omissions limit what can be inferred about the planning and conduct of the study beyond the design elements explicitly recorded.

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: After completing all screening assessments and meeting all eligibility criteria, participants were randomized in a 1:1:1:1 ratio to one of four treatment groups.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The full analysis set included all randomized participants; missing data were analyzed using the non-responder imputation method.

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 Percentage of Participants Who Achieved Clinical Remission at Week 6, measured over Week 6.

The primary endpoint is the percentage of participants who achieved clinical remission at Week 6. Remission was defined as a CDAI score of ≤ 150 points. The Crohn’s Disease Activity Index (CDAI) combines weighted information about eight disease variables: stool frequency, abdominal pain severity, general well-being, extra-intestinal manifestations or fistula, use of antidiarrheal agents, abdominal mass, hematocrit, and body weight. Scores range from 0 to 600, with higher scores indicating greater disease activity.

A threshold-based endpoint gives a clinically interpretable way to classify whether a participant met the registry’s remission definition at the assessment time. It turns a continuous disease-activity score into a binary outcome: remission or not remission under that definition. The percentage in each group therefore describes the frequency of meeting the threshold, rather than the average CDAI score or the size of each participant’s change.

This endpoint does not capture every aspect of disease status, and the result is tied to the specific Week 6 assessment and CDAI threshold. The registry record does not report the duration of remission or a later primary assessment. Missing primary-endpoint data were handled using non-responder imputation, meaning missing outcomes were classified as not achieving remission in the primary analysis population. The record’s definition and missing-data rule should be kept in view when interpreting the percentages.

7. Results Posted in the Registry

• Brodalumab 210 mg: 3.1% (1/32) versus 3.1% (1/32) on control; risk difference 0.0 percentage points (95% CI -8.5 to 8.5), risk ratio 1.00 (0.07–15.30); unadjusted two-proportion z-test p = 1.000.
• Brodalumab 350 mg: 15.2% (5/33) versus 3.1% (1/32) on control; risk difference 12.0 percentage points (95% CI -1.6 to 25.7), risk ratio 4.85 (0.60–39.25); unadjusted two-proportion z-test p = 0.094.
• Brodalumab 700 mg: 9.1% (3/33) versus 3.1% (1/32) on control; risk difference 6.0 percentage points (95% CI -5.5 to 17.5), risk ratio 2.91 (0.32–26.53); unadjusted two-proportion z-test p = 0.317.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants Who Achieved a CDAI Response at Week 6

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Brodalumab 210 mg: 16.1% (5/31) versus 12.5% (4/32) on control; risk difference 3.6 percentage points (95% CI -13.7 to 20.9), risk ratio 1.29 (0.38–4.36); unadjusted two-proportion z-test p = 0.681.
  • Brodalumab 350 mg: 27.3% (9/33) versus 12.5% (4/32) on control; risk difference 14.8 percentage points (95% CI -4.3 to 33.8), risk ratio 2.18 (0.75–6.38); unadjusted two-proportion z-test p = 0.137.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Brodalumab 210 mg 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 Brodalumab 350 mg and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in CDAI at Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Brodalumab 210 mg: mean -8.70 versus -28.20 on control; difference 19.50 (95% CI -26.23 to 65.23), standardized effect d = 0.22; z-test p = 0.403.
  • Brodalumab 350 mg: mean -35.40 versus -28.20 on control; difference -7.20 (95% CI -53.95 to 39.55), standardized effect d = -0.07; z-test p = 0.763.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Brodalumab 210 mg 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 Brodalumab 350 mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary endpoints broaden the picture beyond the Week 6 remission threshold. They include CDAI response, change in CDAI, treatment-emergent adverse events, and pharmacokinetic measures of brodalumab. Together, they cover a related but not identical set of questions: symptom or disease-activity outcomes, safety reporting, and drug exposure. The registry record lists these outcomes, but does not provide a single overall summary that combines them.

The posted secondary results should be considered alongside the primary result rather than as independent confirmation of it. CDAI response and change in CDAI are related to disease activity, but they use different endpoint definitions from remission. Agreement or disagreement among related measures can be informative, yet it does not replace the primary analysis or resolve its uncertainty. Pharmacokinetic measures address drug concentration and timing, not whether participants achieved the clinical endpoint.

Secondary results generally carry less weight when many outcomes, groups, or comparisons are examined without a reported multiplicity plan. Repeated testing increases the chance of seeing an apparently notable result by chance. The registry record does not report whether secondary analyses were adjusted for multiplicity, which outcomes were designated exploratory, or a hierarchy for interpreting them. It would therefore be inappropriate to select an isolated secondary result as definitive evidence.

The posted secondary analyses also have differences in available group summaries and comparison coverage. The registry does not report every possible pairwise comparison for every endpoint. Missing details about analysis populations, model specifications, and multiplicity further constrain comparisons across outcomes. The overall secondary pattern is best treated as descriptive and hypothesis-generating, interpreted in the context of the primary result and the trial’s limited follow-up.

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

• Percentage of Participants Who Achieved a CDAI Response at Week 6
• Change From Baseline in CDAI at Week 6
• Number of Participants With Treatment-emergent Adverse Events (TEAEs)
• Maximum Observed Concentration (Cmax) of Brodalumab
• Time to Maximum Observed Concentration (Tmax) of Brodalumab
• Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab
• Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab

9. Statistical Interpretation

10. Statistical Methods Explained

For a binary endpoint such as remission, each participant either meets the endpoint definition or does not. The percentage in an arm is the proportion classified as having the event. A risk difference compares those proportions by subtraction; a value of zero corresponds to equal observed proportions. A confidence interval for a risk difference describes a range of values compatible with the data under the method used. It is not a guarantee that the true difference lies in that range.

The recalculated pairwise comparisons are unadjusted comparisons of each brodalumab dose with placebo. “Unadjusted” means they do not incorporate a covariate adjustment or a correction for testing multiple comparisons in the values shown. The recalculated p-values and intervals are based on the posted group summaries, and they are not a replacement for the sponsor’s prespecified analysis. The record flags a discrepancy; accordingly, the sponsor’s own analysis takes precedence when interpreting the official trial analysis.

The registry reports chi-squared analyses for the primary pairwise differences in response rate, as well as an overall trend test across all four arms. A chi-squared test evaluates whether the observed event frequencies are consistent with no association between group and event, under the test’s assumptions. The overall trend test addresses a different question from separate pairwise comparisons. The exact trend-test specification is not reported in the registry record.

For the posted secondary change-from-baseline CDAI outcome, the sponsor reports ANCOVA analyses for comparisons with placebo. ANCOVA is a regression approach that can compare outcomes between groups while accounting for a covariate, commonly a baseline measure. The exact model specification and covariates are not reported in the registry record. The recalculated mean differences instead compare posted summary means without that adjustment; they should not be treated as reproductions of the sponsor’s ANCOVA results.

Confidence intervals and p-values answer related but distinct questions. The interval communicates the range and precision of an estimated effect, while a p-value measures how inconsistent the data are with a specified null hypothesis under a statistical model. A p-value is not the probability that the null hypothesis is true, nor does it describe the clinical importance of an effect. A result that does not meet a conventional threshold does not establish equivalence or show that the groups are the same.

The primary analysis population included all randomized participants, according to the record. Non-responder imputation classified missing primary outcomes as failures to achieve remission. This rule makes the missing-data assumption explicit, but it does not eliminate uncertainty about outcomes that were not observed. The registry record does not report the number of missing primary outcomes by group or sensitivity analyses using alternative assumptions.

The planning illustrations use the observed effect as a reference and show participants per arm under stated assumptions: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. These values are planning illustrations, not observed power and not the trial’s own sample-size justification. The registry record does not report that the trial was designed using these calculations. Such illustrations also depend on the observed effect, which can be unstable in a small study, and should not be interpreted as a guarantee that a future study would achieve a particular result.

Over-dispersion is relevant in some outcome models when observed variability exceeds what a simpler model assumes. In general, failing to allow for over-dispersion can make uncertainty appear too small. The primary endpoint is binary, and the registry record does not report an over-dispersion model or an analysis requiring that adjustment. Its relevance should therefore be understood as a general statistical consideration, not as a feature documented for this trial.

What does the risk difference describe?

It expresses the difference between the observed proportions meeting the endpoint in two groups. Its sign indicates which group had the higher observed proportion, while the interval conveys uncertainty about the magnitude. When the interval includes zero, the data are compatible with no difference as well as with values on either side of zero.

Why do recalculated and sponsor analyses differ?

Different statistical procedures, rounding, and analysis specifications can produce different results from the same trial. The record does not fully explain the discrepancy. The recalculations are explicitly simple, unadjusted calculations from posted summaries; they cannot reproduce an analysis whose complete specification is not reported. For that reason, the sponsor-reported values are the relevant official analysis, while recalculations offer a secondary check on the summaries.

11. Confidence Intervals and Precision

Precision is reflected in how wide an uncertainty interval is around an estimated difference. For the primary outcome, the sponsor-reported 95% confidence intervals are -0.09 to 0.09 for 210 mg versus placebo, -0.02 to 0.26 for 350 mg versus placebo, and -0.06 to 0.17 for 700 mg versus placebo. Each interval spans zero, so the reported data remain compatible with no difference between the compared groups.

The recalculated unadjusted intervals are also broad relative to their point estimates: -0.085 to 0.085 for 210 mg, -0.016 to 0.257 for 350 mg, and -0.056 to 0.175 for 700 mg. These intervals should be distinguished from the sponsor’s intervals because the record flags a discrepancy and the sponsor analysis takes precedence. The displayed precision of a decimal estimate does not mean the underlying effect is known with similar precision.

In general, a confidence interval describes uncertainty under the analysis method and assumptions used; it is not a probability statement about a fixed parameter. Wider intervals indicate less precision. When an interval includes zero, it does not prove that the true effect is zero. It indicates that the data do not rule out zero under that analysis, while also allowing a range of positive and negative differences.

The trial’s group sizes and the low observed remission percentages make the primary comparisons especially uncertain. The registry record does not provide a sample-size justification or state the target precision. Planning illustrations elsewhere use the observed effect and explicit assumptions, but they should not be confused with precision achieved in this trial or with observed power.

12. Analyses Reported by the Sponsor

The registry reports sponsor analyses for the primary endpoint using an overall trend test and chi-squared pairwise comparisons. The sponsor’s reported pairwise differences are < 0.001 for 210 mg versus placebo, 0.120 for 350 mg versus placebo, and 0.060 for 700 mg versus placebo. Their 95% confidence intervals are -0.09 to 0.09, -0.02 to 0.26, and -0.06 to 0.17, respectively. The corresponding p-values are 1.000, 0.097, and 0.321.

The recalculated comparisons are simple unadjusted re-calculations from the posted group summaries. Their confidence limits and p-values differ slightly from the sponsor’s figures, particularly for the 350 mg comparison. The record marks this as a discrepancy but does not explain its source. Differences can arise from the details of the analysis method, but the exact reason is not reported in the registry record.

Accordingly, the sponsor’s own analysis takes precedence as the official trial analysis. The recalculation is best treated as a check on the direction and broad scale of the posted summaries, not as a correction to the sponsor’s result. Both sets of intervals include zero, and the sponsor’s reported pairwise p-values do not provide clear evidence of a difference from placebo. The reported overall trend-test p-value is 0.194; the registry does not report additional detail about that test’s specification.

13. Multiplicity, Missing Data and Analysis Populations

The primary analysis population is described as the full analysis set, including all randomized participants. For the primary endpoint, missing data were handled using non-responder imputation: a participant with a missing outcome was counted as not achieving clinical remission. This is an analysis rule, not a direct observation of the missing participant’s outcome. Its effect depends on how much data were missing and whether the assumption is appropriate; the registry record does not report the missing-outcome counts by arm or sensitivity analyses.

Several doses were compared with placebo, and the registry also lists multiple secondary outcomes. When many hypotheses are tested, the chance of at least one apparently unusual result can increase. Statistical methods can control that risk, for example by adjusting for multiple comparisons or specifying a hierarchy of tests. Whether such methods were planned for the primary pairwise comparisons or secondary outcomes is not reported in the registry record. The overall trend test is reported, but its relationship to a testing hierarchy is not described.

The sponsor’s primary analyses and the simple recalculations are not interchangeable. The sponsor reports chi-squared comparisons and an overall trend test. Recalculations use posted summaries without covariate adjustment. The exact source of the noted discrepancy is not reported, and the sponsor’s own analysis takes precedence. The full analysis plan, including handling of protocol deviations and the exact specifications for secondary models, is not reported in the registry record.

Because missing-data details, sensitivity analyses, and multiplicity procedures are unavailable, the statistical evidence should be read cautiously. These limitations do not invalidate the posted results, but they mean that the record alone does not establish how robust the findings are to alternative missing-data assumptions or to accounting for the number of outcomes examined.

14. 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 (21.2%), abdominal pain (6.2%), diarrhoea (3.2%), anal abscess (3.2%), dysphagia (3.1%).

The registry reports serious adverse events and other adverse events by treatment group. For serious adverse events, the reported affected counts are 2 with placebo, 3 with brodalumab 210 mg, 8 with brodalumab 350 mg, and 9 with brodalumab 700 mg. The corresponding at-risk counts are 32, 31, 32, and 33. The other-adverse-event field reports affected counts of 20, 21, 23, and 20, respectively, with at-risk counts of 32, 31, 32, and 33.

These are descriptive counts from the registry, not adjusted comparisons of safety risk. The record does not provide confidence intervals or comparative statistical analyses for these figures. A difference in counts cannot by itself establish a treatment-related cause or a difference in underlying risk, particularly without further detail about event definitions, exposure time, severity, and participant-level event patterns.

The registry lists serious adverse-event terms including Crohn’s disease at 21.2%, abdominal pain at 6.2%, diarrhoea at 3.2%, anal abscess at 3.2%, dysphagia at 3.1%, and nausea at 3.1%. These term percentages are not presented by treatment arm in the record, and the denominator for each term is not reported in the registry record. Death counts are not reported in the registry record. The safety figures therefore describe what the record lists, not a complete comparative safety assessment.

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

The primary endpoint results describe the percentage of participants meeting the registry’s CDAI remission definition at Week 6. The percentages varied across the placebo and brodalumab groups, but the sponsor-reported confidence intervals for each dose comparison include no difference. The overall trend-test p-value also does not provide clear evidence of an overall difference across the groups. These findings are uncertain, not proof that the groups are identical.

The endpoint is specific to a threshold on the CDAI and a single reported assessment time. It does not establish how long remission lasted, whether disease activity changed later, or how results would compare in populations beyond the trial participants. The registry record does not report longer-term primary outcomes. It also does not report the reason the trial was terminated, and that status should not be treated as evidence about the clinical results.

The estimates do not establish that brodalumab works or does not work. They show the posted outcomes and the uncertainty around comparisons under the reported analyses. The trial was phase 2, and the registry does not provide a sample-size justification or a complete statistical analysis plan. Consequently, the results cannot be used to infer that a clinically meaningful effect was ruled out or that any observed arm percentage represents a stable effect.

Nor do these outcome results alone determine safety. Adverse-event counts are descriptive and the record does not provide comparative safety analyses or event-level context sufficient to attribute events to treatment. Overall, the most defensible interpretation is limited to the specific Week 6 outcome, the reported group summaries, and the statistical uncertainty documented in the registry record.

16. Why This Trial Matters Statistically

This trial illustrates several important issues in clinical-trial interpretation. First, the choice of endpoint matters: a remission threshold gives a clear classification but does not convey the full pattern of CDAI scores or their changes. The secondary change-from-baseline measure addresses a different aspect of disease activity, so endpoints should not be treated as interchangeable.

Second, observed percentages and comparative evidence are not the same thing. A larger percentage in an arm is a descriptive difference; confidence intervals show that the estimated contrast remains uncertain. Reading the interval alongside the point estimate helps prevent a single percentage or p-value from carrying more meaning than the data support.

Third, the record’s discrepancy between sponsor analyses and simple recalculations shows why analysis method and provenance matter. Summary-data re-calculations may be useful checks, but they cannot replace the trial’s official analysis when the record identifies a discrepancy. The sponsor’s analysis takes precedence, while incomplete reporting of its details limits independent reconstruction.

Finally, the record leaves important planning and interpretation details unspecified. The sample-size justification, multiplicity procedures, and reason for termination are not reported. These omissions make it harder to determine the intended precision, how multiple outcomes were to be weighed, and the context for the study’s status. This is a useful case for separating what is directly reported from what remains uncertain.

17. 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.

Several trial-specific limitations constrain interpretation. The primary endpoint is measured at Week 6, and the registry record does not report a longer-term primary assessment. The result therefore addresses the reported short-term remission outcome, not durability or later disease status. The study is listed as terminated, but the reason for termination is not reported in the registry record.

The primary analysis used non-responder imputation for missing outcomes, but the record does not report the number of missing outcomes by group or sensitivity analyses. This makes it difficult to assess how dependent the result is on that assumption. Although the analysis population is described as all randomized participants, the registry does not give a full account of protocol deviations or other analysis-population details.

The discrepancy between recalculated unadjusted comparisons and sponsor-reported analyses is another limitation. The sponsor’s own analysis takes precedence, but the record does not explain the source of the difference or provide a complete analysis specification for independent reproduction. The sample-size justification, multiplicity approach, interim-analysis plan, and detailed statistical analysis plan are not reported in the registry record.

For safety, the registry provides group counts and a list of serious adverse-event terms, but not comparative uncertainty estimates or enough event-level context to attribute events. The denominator for the listed term percentages is not reported in the registry record. The secondary outcomes also cover different questions and do not have a reported multiplicity framework, limiting how strongly they can be used to support a unified conclusion.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Brodalumab (AMG 827) in Adults With Moderate to Severe Crohn's Disease — NCT01150890.
• Registry record last updated 2022-01-03; status last verified 2021-11.
• Results first posted 2022-01-03.
• 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.

21. Record Summary

The registry describes a randomized, double-blind, parallel-group phase 2 trial of brodalumab versus placebo in adults with moderate to severe Crohn’s disease. Participants received intravenous treatment at baseline and Week 4, with three brodalumab dose groups and a placebo group. The primary outcome was clinical remission at Week 6, defined by CDAI ≤ 150.

Remission percentages ranged from 3.1% to 15.2% across the posted groups. Sponsor-reported comparisons with placebo had 95% confidence intervals that included no difference, and the reported overall trend-test p-value was 0.194. A discrepancy is flagged between sponsor results and simple unadjusted recalculations; the sponsor’s own analysis takes precedence.

The record lists secondary disease-activity, safety, and pharmacokinetic outcomes. Missing primary outcomes were handled by non-responder imputation. The trial is marked terminated, but the reason is not reported. The registry record does not report a sample-size justification, a multiplicity plan, or a complete statistical analysis plan.