Extension Trial Assessing the Safety and Efficacy of BI 655066/ABBV-066/Risankizumab in Patients With Moderate to Severe Chronic Plaque Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension Trial Assessing the Safety and Efficacy of BI 655066/ABBV-066/Risankizumab in Patients With Moderate to Severe Chronic Plaque Psoriasis (NCT02203851), a non-randomized phase 2 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

The study is an extension trial rather than a new randomized comparison. Its question is whether adverse events were reported during extended exposure among participants who entered the study, and how the registry describes those events in the two dosing groups. It also set out to further investigate long-term efficacy, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. Those objectives are not equivalent to evidence from a controlled comparison: interpretation depends on what was measured, who remained under observation, and how outcomes were analyzed. The registry record does not report a comparison group receiving a different treatment or no study drug.

3. Trial Design

This completed Phase 2 study was an open-label, non-randomized, single-group extension trial sponsored by AbbVie. Its title identifies risankizumab, also referred to by the registry title as BI 655066/ABBV-066, and its population as patients with moderate to severe chronic plaque psoriasis. The enrollment was 110. The registry lists the study start as 2014-11-20 and primary completion as 2018-09-04.

Participants entered the extension receiving risankizumab 90 mg by subcutaneous injection. The dosing groups were then defined by the Week 12 response: participants who achieved PASI90 continued open-label 90 mg, while participants who achieved less than PASI90 switched to open-label 180 mg. The record describes dosing at Week 12 and every 12 weeks, but the dosing descriptions are incomplete in the registry record, so further details of the schedule are not reported in the registry record.

This response-based grouping matters statistically. The groups began with different Week 12 response histories, and their treatments were not allocated randomly. Differences in later outcomes could reflect those starting differences, ongoing disease course, exposure, or other factors, as well as dose. The groups are not a like-for-like control comparison, and their outcomes should not be read as a randomized estimate of the effect of 90 mg versus 180 mg.

The primary objective was safety during long-term treatment. The registry lists a primary endpoint of the number of participants with treatment-emergent adverse events and secondary outcomes including several PASI thresholds and static Physician Global Assessment outcomes at Week 48 of the extended dosing period. Numerical results for these endpoints are not reported in the registry record. Details of eligibility criteria, the complete dosing schedule, and the statistical analysis plan are not reported in the registry record.

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: Participants completing lead-in study and met eligibility for this study were enrolled; demographic/disposition were not collected by dose level. Some participants in extension study had dose escalation due to lack of efficacy, predefined selected safety analysis were broken down by groups: participants remaining at 90mg and those receiving 180mg.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population, which is the same as the Intent to Treat (ITT) population for this study (defined as all participants who received at least one dose of study drug in the study), summarized by the group the participants who remained at 90 mg throughout the study and the participants who received 180 mg

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: Intent to Treat (ITT) Population: All participants that received at least one dose of study drug in the extension study who either remained at 90 mg throughout the study or who received 180 mg were summarized.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs), measured over From first dose of study drug in either the lead-in or extension study until 12 weeks after the last dose of study drug (approximately 4 years from the first dose in either the lead-in or extension study).

The primary endpoint counts participants with treatment-emergent adverse events, rather than measuring change in psoriasis severity. An adverse event is an untoward medical occurrence after a pharmaceutical product is administered; the registry definition does not require that the event be caused by treatment. The investigator assessed each event’s relationship to study drug using categories ranging from probably related to not related. A treatment-emergent event was defined as one with onset after the first risankizumab dose in this study.

The stated observation window runs from the first dose in either the lead-in or extension study until 12 weeks after the last study-drug dose, described as approximately 4 years from the first dose in either study. Counting participants with events is a way to describe how many people experienced an event during that window. The endpoint is relevant to a safety objective because it focuses on occurrence among treated participants; it does not, by itself, establish that treatment caused an event or capture its full clinical severity, duration, or consequences.

The registry defines the safety population as the same as the Intent to Treat population in this study: all participants who received at least one dose. However, the numerical result for the primary endpoint is not reported in the registry record. The posted adverse-event counts include serious and other adverse-event figures, but do not provide a reported total for the primary treatment-emergent endpoint. The extent to which those categories cover the complete primary endpoint is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what this record can and cannot establish. The first is the distinction between a count and an estimated rate. The primary endpoint is defined as a number of participants with treatment-emergent adverse events. A count is directly interpretable as the number of people recorded with an event in a specified group, but it does not communicate the frequency without a clearly stated denominator and outcome definition. The registry posts group counts for serious and other adverse events, while the numerical result for the full primary endpoint is not reported in the registry record.

Why the group structure matters

Random allocation is one way to make groups comparable, on average, at the start of a treatment comparison. This study was non-randomized and single-group, and the extension dose groups followed a response-based rule. Participants who achieved PASI90 at Week 12 continued 90 mg; those who achieved less than PASI90 switched to 180 mg. The groups therefore differed in the response that led to their dosing paths. A difference in later outcomes could arise from that selection, from dose, or from other factors. The registry record does not report a statistical adjustment designed to separate these explanations.

For that reason, a comparison of the posted counts is descriptive. It does not estimate the causal effect of assigning one dose rather than another in otherwise comparable participants. Even a numerical difference between group counts would be difficult to interpret without considering the different group sizes, time under observation, and potential differences in exposure. No calculation of a comparative effect or uncertainty is reported in the registry record.

What uncertainty measures would add

A confidence interval is a statistical range around an estimate that communicates how imprecisely the data estimate an underlying quantity under the assumptions of the method. It is not a guarantee that the true value lies in the interval, and it does not correct a biased comparison or an unsuitable design. The registry record does not report confidence intervals for the primary endpoint or the posted group counts. Without them, the precision of an estimated event frequency or contrast cannot be assessed from the record.

A hypothesis test and its p-value address a different question: how compatible the observed data are with a specified statistical model and null hypothesis. A p-value is not the probability that a treatment is effective or that the null hypothesis is true. No p-value or inferential test for the primary endpoint is reported in the registry record. In this non-randomized extension setting, a test alone would not resolve the limitations created by response-based group assignment.

Safety-event classification

The endpoint description distinguishes an adverse event from a serious adverse event. The definition of an adverse event does not require a causal link to study drug. Investigators assessed relatedness using categories from probably related to not related. Treatment-emergent status is based on onset after the first dose in this study. These are separate concepts: an event can meet the timing definition without being judged related to treatment, and seriousness describes the event’s consequences or importance rather than its causal attribution.

The registry’s serious-event terms include individual diagnoses with percentages, but the record does not give the corresponding details needed to interpret those percentages fully. In particular, the event-level counts, group-specific distribution, and attribution for each term are not reported in the registry record. A listed percentage should therefore not be reinterpreted as a comparative risk or as evidence of causation.

Planning calculations and observed evidence

The record describes sample-size illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning illustrations: they ask what sample size might be needed under stated assumptions to detect an assumed effect. They are not observed power, do not show what this trial was designed to detect, and do not add evidence about the outcomes actually observed. The registry record does not report the trial’s own sample-size justification, and numerical planning results are not reported in the registry record.

The stated illustration assumes equal allocation, whereas the posted group sizes are unequal. That difference further separates a planning scenario from the actual extension cohort. The record does not report the effect value or the numerical sample-size outputs needed to interpret a particular planning row. No conclusion about adequacy of the trial’s enrollment for a specific target effect can be drawn from the registry record.

Over-dispersion and repeated observations

General statistical context: over-dispersion occurs when observed variability exceeds what a chosen statistical model expects. It can make standard errors too small if the model does not account for that extra variability. This is especially relevant in some count-data settings, where participants may contribute different numbers of events or have different follow-up. The primary endpoint is described as a count of participants with events, not a count of every event, and the registry record does not report a model for repeated events or an over-dispersion assessment.

More generally, a long observation window can involve differing exposure durations if participants start or stop treatment at different times. Comparing raw numbers alone may not account for different time at risk. The registry gives an approximate overall endpoint window, but participant-level follow-up distributions and time-adjusted analyses are not reported in the registry record. These omissions limit how finely the event counts can be interpreted.

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("Risankizumab 90 mg", "Risankizumab 180 mg")
n      <- c(87, 23)
events <- c(67, 18)
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  Risankizumab 90 mg  87  67  77.0  66.8  85.4  67.1  84.6  67.1  84.6
ARM  Risankizumab 180 mg  23  18  78.3  56.3  92.5  58.1  90.3  57.8  90.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary efficacy outcomes, including static Physician Global Assessment and PASI thresholds at Week 48 of the extended dosing period. When multiple outcomes are evaluated, the chance of finding an apparently notable result by chance can increase if each is tested separately. Statistical plans may address this through a prespecified hierarchy or an adjustment for multiple comparisons. The registry record does not report whether such a plan or adjustment was used. Numerical results for the listed secondary outcomes are also not reported in the registry record.

Missing-data handling is another important part of interpreting outcomes at a fixed visit. Participants may not have a Week 48 measurement for reasons such as discontinuation or missed assessment. Analyses can use different assumptions or procedures for missing values, and those choices can affect estimates. The registry record does not report the amount or pattern of missing data for the listed efficacy outcomes, how missing measurements were handled, or sensitivity analyses assessing the impact of those choices.

The primary safety population is defined as all participants who received at least one dose and is described as the same as the Intent to Treat population. The record also says results were summarized by groups based on whether participants remained at 90 mg or received 180 mg, but the full population description is incomplete. The posted group counts give denominators of 87 and 23 for the safety figures. Further details on exclusions, withdrawals, or population-specific analysis sets are not reported in the registry record.

The registry record does not report a full statistical analysis plan, interim analyses, multiplicity procedures, or a detailed accounting of missing outcome data. These gaps prevent assessment of whether analyses were prespecified and how sensitive conclusions might be to analysis choices. No primary-endpoint inferential analysis is reported.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (4.3%), basal cell carcinoma (4.3%), carpal tunnel syndrome (4.3%), ulnar neuritis (4.3%), psychotic disorder (4.3%).

The safety figures list serious adverse events for 12 of 87 participants in the 90 mg group and 2 of 23 in the 180 mg group. Other adverse events are listed for 46 of 87 and 15 of 23 participants, respectively. The record lists 0 deaths in each group. These are descriptive counts from an extension study, not a randomized comparison between doses.

The listed serious-event terms are pneumonia, basal cell carcinoma, carpal tunnel syndrome, ulnar neuritis, psychotic disorder, and chronic obstructive pulmonary disease. Each is reported with a percentage of 4.3%. The registry record does not provide the event-level counts or group distribution for each term, so the listed percentages should not be used to infer how many participants in each group experienced each event.

An adverse event is not necessarily caused by study drug. The investigator assessed relatedness, but the group-level relatedness results are not reported in the registry record. Seriousness is defined by outcomes such as death, life threat, hospitalization, persistent disability, congenital anomaly, or another medically important event. The registry counts alone do not describe timing, duration, severity beyond classification, or the total number of events per participant. They also do not establish comparative safety.

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

The record describes a completed extension study in which participants received open-label risankizumab and dosing groups were based on PASI90 response at Week 12. Its primary objective was safety during long-term treatment. The posted safety figures provide counts for serious and other adverse events, and list no deaths in either group. Those figures are useful as descriptive information about the participants included in the registry summaries.

They do not show that risankizumab caused or prevented any particular event. The registry’s definition of an adverse event does not require a causal relationship, and the record does not provide group-level investigator assessments of relatedness. Nor do the counts provide a controlled estimate comparing 90 mg with 180 mg. The dose groups were formed through a response-based rule rather than random assignment, so differences between them cannot be interpreted as an isolated dose effect.

The record also does not report a numerical result for the primary endpoint as defined, confidence intervals, or statistical tests. It lists Week 48 efficacy outcomes without numerical results. Therefore, the available record does not establish the magnitude or precision of longer-term efficacy outcomes, nor does it allow those outcomes to be compared with a control group.

More broadly, an extension study can describe observations during continued treatment among participants who entered and remained under observation. It cannot, on its own, answer every question about comparative efficacy or safety. Assessment of event frequency also depends on definitions, observation time, and completeness of follow-up. Details on missing data and participant-level follow-up are not reported in the registry record. The most defensible reading is therefore descriptive: the record contains safety counts in two response-defined dosing groups, but does not provide the information required for a causal or precise comparative conclusion.

14. Why This Trial Matters Statistically

Extension studies address a statistical question that differs from the question addressed by a randomized controlled trial. They can collect information about safety and other outcomes during continued exposure after an earlier treatment period. This study’s stated objective was to investigate safety during long-term treatment, with additional objectives covering efficacy, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. The registry identifies an observation window extending until 12 weeks after the last dose, described as approximately 4 years from the first dose in either the lead-in or extension study.

The design also illustrates why group labels need careful interpretation. The 90 mg and 180 mg groups were formed according to the Week 12 PASI90 response, rather than randomized assignment. This is consequential because the same clinical response that defined the dose path may also relate to later outcomes. Treating the groups as if they were comparable treatment arms would overstate what their contrast can establish.

Statistically, the record is also a reminder that an endpoint definition and a numerical result are different pieces of evidence. The registry defines the primary safety endpoint and the time window, but does not report its numerical result or uncertainty. Counts for serious and other adverse events add descriptive information, yet they do not substitute for a complete endpoint analysis or a controlled comparison.

For clinical researchers and biostatisticians, this distinction helps keep interpretation aligned with design and reporting. A long follow-up objective can be important while still leaving uncertainty about comparative effects, event attribution, missing outcomes, and precision. The record’s limitations are not resolved by the size of a group count or by listing endpoint names. They identify what additional analysis and transparent reporting would be needed to support stronger statistical conclusions.

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 interpreting treatment differences is the non-randomized, single-group extension design. Participants were sorted into dose paths by their Week 12 response: PASI90 responders continued 90 mg, while those with less than PASI90 switched to 180 mg. The resulting groups are not comparable by random assignment. Differences in subsequent safety or efficacy observations could reflect the response-based selection as well as dose or other factors.

The registry lists 87 participants at risk in the 90 mg group and 23 in the 180 mg group. These group sizes are unequal, and the record does not report a controlled comparison or an adjustment addressing the design. The enrollment of 110 does not by itself indicate how many participants contributed to each particular outcome, how much follow-up they contributed, or whether all participants had the same observation time.

The primary endpoint is defined, but its numerical result is not reported in the registry record. Confidence intervals, hypothesis tests, and a detailed analysis plan are also not reported. The record lists several secondary efficacy outcomes without numerical results. It does not report multiplicity handling, missing-data methods, the completeness of outcome assessments, or participant-level follow-up patterns. The full dosing descriptions are incomplete, and additional protocol details are not reported in the registry record.

Finally, the adverse-event categories and listed serious-event terms do not provide all information needed to assess event timing, participant-level recurrence, causal attribution, or group-specific distribution by term. The registry’s event definition allows events not caused by study drug to be counted. Taken together, these limitations mean that the posted safety counts should be read descriptively and that conclusions about comparative effects or precision are not supported by the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Extension Trial Assessing the Safety and Efficacy of BI 655066/ABBV-066/Risankizumab in Patients With Moderate to Severe Chronic Plaque Psoriasis — NCT02203851.
• Registry record last updated 2019-11-08; status last verified 2019-10.
• Results first posted 2019-11-08.
• 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

NCT02203851 is a completed Phase 2, open-label, non-randomized, single-group extension study sponsored by AbbVie. It enrolled 110 participants with moderate to severe chronic plaque psoriasis and investigated long-term risankizumab safety, with additional objectives concerning efficacy, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity.

Participants entered receiving 90 mg. Those who achieved PASI90 at Week 12 continued at 90 mg, while those who achieved less than PASI90 switched to 180 mg. The primary endpoint was the number of participants with treatment-emergent adverse events. The registry lists serious and other adverse-event counts and 0 deaths in each group, but the numerical result for the primary endpoint is not reported in the registry record. The Week 48 secondary efficacy outcomes are listed without numerical results. Because dosing groups were response-defined rather than randomized, their outcomes are descriptive and do not provide a like-for-like dose comparison.