Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC) (NCT01716039), a randomized phase 2 study. The primary outcome is Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.

2. Clinical Question

Statistically, the question is whether the observed score changes differ across the methotrexate and placebo groups receiving adalimumab. The posted arm summaries give mean changes and standard deviations, while the reported pairwise analyses give Wilcoxon (Mann-Whitney) p-values for placebo versus each methotrexate dose. Those p-values address evidence against a no-difference comparison under the respective test; they do not quantify the size or precision of a treatment-group contrast.

3. Trial Design

NCT01716039 is described as a phase 2, randomized, triple-masked, parallel-group study sponsored by Alimentiv Inc. Its title identifies pharmacokinetics of adalimumab with methotrexate for treatment of ulcerative colitis, and the registry summary describes assessment of the dose-response relationship for the adalimumab–methotrexate interaction. The study status is terminated. The recorded start is 2013-06, and primary completion is dated 2016-07-18.

Three groups are described: adalimumab with oral methotrexate 12.5 mg once weekly, adalimumab with oral methotrexate 25 mg once weekly, and adalimumab with oral placebo once weekly. The arm descriptions state that the oral dosing began two weeks before adalimumab and continued for 18 weekly doses alongside adalimumab. Further details of adalimumab dosing are not reported in the registry record.

The registry enrollment is 22. The primary-outcome summaries list 4 participants in the placebo group, 8 in the MTX 12.5mg group, and 10 in the MTX 25 mg group. In contrast, the intervention descriptions include planned arm counts of 40, 40, and 20. The record does not explain this difference, so the intervention-description counts should not be treated as the numbers contributing to the posted outcome summaries.

The primary outcome is change in modified Baron score from baseline to Week 18. A secondary outcome is change in Ulcerative Colitis Endoscopic Index of Severity score from baseline to Week 18 between treatment groups. The registry record lists two outcome measures and three analyses, but does not provide further detail about the conduct or completion of the secondary outcome analyses.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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 Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups, measured over Baseline up to Week 18.

The primary endpoint is change in the modified Baron score from baseline to the final visit at Week 18. The score evaluates friability, vascular pattern, bleeding, and ulceration. It is described as a score on a 0–4 scale, with the features graded on a 5-point scale; higher scores indicate more severe disease activity.

A change score summarizes how the measured endoscopic disease activity differs between the starting assessment and the Week 18 assessment. Comparing changes between groups focuses on differences in trajectories over the study period, rather than comparing only the final scores. Endoscopic scoring is used to assess visible features of disease in the colon, providing an outcome distinct from symptoms or laboratory measurements. Those other outcome domains are not described as the primary endpoint in this record.

The registry description states that the mean change and 95% confidence interval are based on least-squares means from an analysis of covariance. However, the posted arm summaries give mean changes and standard deviations, and do not include arm-specific confidence intervals. The record also does not post a numerical least-squares contrast estimate or its confidence interval. Therefore, the score’s clinical measurement purpose can be described, but the precision of the primary between-group effects cannot be read from the posted primary-outcome results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the arm summaries represent?

The posted primary outcome is a continuous measure, and the registry labels the reported arm value as a mean. A mean is the arithmetic average of the participants’ change scores in a group. The standard deviation describes how dispersed those individual scores are around the group mean. It is not a confidence interval for the group mean and does not describe the uncertainty in a between-group effect by itself.

The arm means are 0.7 for placebo, 1.1 for MTX 12.5mg, and 0.9 for MTX 25 mg, with standard deviations of 1.2, 1.6, and 1.8, respectively. They are unadjusted group summaries in the posted results. The endpoint description separately says that mean change and a 95% confidence interval are based on least-squares means from an analysis of covariance. The corresponding least-squares values and intervals are not reported in the registry record.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity using a range of values compatible with the data and the method’s assumptions. For a treatment-group contrast, it helps readers assess both the direction and the precision of the estimated difference. A narrow interval indicates greater precision than a wide interval, while an interval spanning values in both directions may leave the direction uncertain. These are general interpretations; no numerical primary contrast interval is posted for this outcome.

Why might the methods differ?

The endpoint description mentions least-squares means from analysis of covariance, while the reported pairwise comparisons use the Wilcoxon (Mann-Whitney) method. In general, analysis of covariance models an outcome while adjusting for one or more covariates, potentially including baseline score. The registry record does not identify the covariates used or provide the model specification. The Wilcoxon (Mann-Whitney) procedure is a rank-based comparison of two groups. It does not report the adjusted mean difference described in the endpoint text. The record does not explain whether the rank-based comparisons were additional, substituted, or intended as the primary inferential analyses.

Because these methods target and summarize group differences differently, their results should not be treated as interchangeable. A p-value from a rank-based test is not an estimate of an adjusted mean change difference. A reader seeking the size and precision of the primary contrast would need the corresponding estimate and confidence interval, which are not reported in the registry record.

How should the p-values be read?

The posted p-values are 0.758 for placebo versus MTX 12.5mg and 1.00 for placebo versus MTX 25 mg. In general, a p-value measures how surprising data at least as incompatible with a specified null hypothesis would be if that hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, nor is it a measure of effect size. A large p-value does not establish that two groups are equivalent. Equivalence requires a defined margin and an analysis designed to assess whether the uncertainty lies within that margin; such a margin and analysis are not reported in the registry record.

The posted results provide two pairwise p-values, but no confidence intervals or estimated contrasts for them. Thus the tests indicate the recorded inferential results, while leaving the size and precision of any group differences unclear. The record does not report a threshold for clinical importance.

What does variability and sample size imply?

In general, higher variability makes it harder to estimate group differences precisely, because individual outcomes are more spread out. Small groups can also yield imprecise estimates and limit the ability to distinguish a real difference from random variation. The reported standard deviations are 1.2, 1.6, and 1.8, and the primary-outcome group counts are 4, 8, and 10. These summaries give context for interpreting the posted comparisons, but they do not permit a reliable reconstruction of the sponsor’s full analysis.

Over-dispersion is a general concern when data vary more than a chosen model expects. It can affect standard errors and confidence intervals if the model does not account for the variability. The registry record does not report a model diagnostic or a specific over-dispersion assessment, and the continuous primary score is summarized using means and standard deviations. It would therefore be inappropriate to claim that over-dispersion was present or that a particular correction was used.

What can be recalculated?

The posted summaries do not support a reported recalculated estimate for the two-arm continuous comparisons; the registry record flags the pairwise continuous comparison values as missing or not estimable. No recalculated contrast, confidence interval, or p-value should therefore be inferred from these summaries. The sponsor’s reported Wilcoxon p-values remain the available inferential results, and the record does not flag a discrepancy between sponsor results and a recalculation.

The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is defined as a fraction of the observed effect. No resulting sample-size figures are included in the record summarized by these results. In general, such figures are planning illustrations, not observed power and not evidence about the trial’s actual operating characteristics.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Placebo", "MTX 12.5mg", "MTX 25 mg")
n   <- c(4, 8, 10)
m   <- c(0.7, 1.1, 0.9)
sp  <- c(1.2, 1.6, 1.8)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Placebo  4  0.700  1.200  -1.209  2.609
CARM  MTX 12.5mg  8  1.100  1.600  -0.238  2.438
CARM  MTX 25 mg  10  0.900  1.800  -0.388  2.188

11. Analyses Reported by the Sponsor

The registry reports the sponsor’s pairwise Wilcoxon (Mann-Whitney) tests: p = 0.758 for placebo versus MTX 12.5mg and p = 1.00 for placebo versus MTX 25 mg. The record does not provide the corresponding test statistics, effect estimates, or confidence intervals. The endpoint description’s reference to least-squares means and analysis of covariance does not include numerical adjusted contrasts.

A recalculated pairwise comparison is not available from the posted summary statistics: the record identifies the continuous comparison values as missing or not estimable. No independently recalculated effect or p-value can therefore be compared with the sponsor’s tests. The discrepancy flag is false, so the registry record does not identify a conflict between sponsor analysis and recalculation. This absence of a flagged discrepancy does not supply the missing estimates or explain the relationship between the ANCOVA description and the Wilcoxon tests.

The sponsor’s p-values should be interpreted as the inferential results actually posted, not as evidence that the treatment groups are equivalent. They do not reveal the size or precision of the group contrasts. Further detail about the analysis population, model specification, and confidence intervals is not reported in the registry record.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists two pairwise primary-outcome comparisons: placebo versus MTX 12.5mg and placebo versus MTX 25 mg. It also lists one secondary outcome, change in Ulcerative Colitis Endoscopic Index of Severity score from baseline to Week 18 between treatment groups. The record does not report a multiplicity adjustment, a hierarchy among outcomes, or a prespecified strategy for controlling the chance of false-positive findings across tests. The posted p-values should therefore be read as the reported results for their individual comparisons, without assuming that any adjustment was or was not applied.

Missing-data handling is not reported in the registry record. The posted primary outcome summaries contain group counts, but the record does not explain whether all randomized participants had Week 18 assessments, how missing baseline or follow-up values were treated, or whether any imputation or sensitivity analysis was performed. No analysis population, such as an intention-to-treat or per-protocol population, is identified in the outcome description.

The registry enrollment is 22, while the intervention descriptions give arm counts of 40, 40, and 20 and the primary outcome summaries give counts of 4, 8, and 10. The record does not explain the discrepancy between the intervention-description counts and the outcome counts. These figures should not be reconciled by assumption. In particular, the primary-outcome counts describe the observations in the posted summaries, not necessarily the trial’s full randomized population.

The study is marked terminated, but details about termination, participant disposition, protocol deviations, or whether termination affected outcome collection are not reported in the registry record. These omissions prevent a full assessment of attrition, analysis-set definition, and the robustness of the reported comparisons.

13. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: colitis ulcerative (12.5%), urosepsis (12.5%).

The serious adverse event summaries report 0 affected participants among 4 at risk in the placebo group, 2 among 8 at risk in the MTX 12.5 mg group, and 1 among 10 at risk in the MTX 25 mg group. The record also lists Colitis ulcerative and Urosepsis as serious adverse event terms, each with a reported percentage of 12.5%. It does not provide enough context to associate those terms with particular groups in this summary.

Other adverse events are reported for 3 participants among 4 at risk in the placebo group, 8 among 8 at risk in the MTX 12.5 mg group, and 5 among 10 at risk in the MTX 25 mg group. These are descriptive counts, not adjusted comparisons. The registry record does not report deaths, and the reason deaths are absent is not stated.

Differences in these counts should be interpreted cautiously because the groups are small and the record does not give event timing, duration of exposure, severity details beyond the serious-event classification, or a comparative statistical analysis. The figures describe what was recorded in each group; they do not establish that an intervention caused or prevented an event.

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

The posted results establish that the registry contains mean change summaries for the modified Baron score and two sponsor-reported pairwise Wilcoxon p-values. The mean changes are 0.7 for placebo, 1.1 for MTX 12.5mg, and 0.9 for MTX 25 mg; their reported standard deviations are 1.2, 1.6, and 1.8. The pairwise p-values are 0.758 and 1.00, respectively. The registry does not provide the primary between-group estimates or confidence intervals needed to quantify the size and precision of those comparisons.

The results do not establish that the groups are equivalent, and they do not establish that any difference is clinically important. A p-value alone cannot answer either question. The record does not identify a threshold for a clinically meaningful change, so the clinical interpretation of the observed score changes cannot be determined from these results alone. The direction of the change score is also not explicitly defined in the record.

The outcome is an endoscopic score of disease activity, not a comprehensive measure of all aspects of ulcerative colitis. The registry record also lists a secondary endoscopic score, but numerical secondary results are not included in the reported details. The primary outcome findings therefore should not be generalized to unreported symptoms, quality of life, or other outcomes.

The trial is marked terminated, and the record does not state why. The discrepancy between the registry enrollment, intervention-description counts, and primary-outcome group counts is unexplained. Missing-data methods, analysis populations, and a multiplicity plan are also not reported. These limitations mean the results are best treated as a limited account of the outcomes and analyses posted in the registry, rather than a complete basis for broad conclusions about the study.

15. Why This Trial Matters Statistically

This trial is statistically notable because its registry record combines several different kinds of information that need to be kept separate: arm-level mean changes, variability measures, rank-based p-values, and a description of an ANCOVA-based mean analysis. A mean and standard deviation describe each group; they do not supply an adjusted between-group estimate. A rank-based p-value does not supply the missing adjusted mean contrast. Recognizing these distinctions prevents the p-values from being mistaken for effect sizes.

The reported outcome counts are small, and the standard deviations are substantial relative to the reported mean changes. In general, estimates from small, variable groups can be imprecise. Without contrast confidence intervals, readers cannot assess that uncertainty directly from the primary results. The absence of a small p-value should not be confused with precise evidence of no difference.

The record also illustrates why participant counts and analysis populations matter. Overall enrollment, arm-description counts, and outcome-summary counts differ, with no explanation recorded. Because the registry does not describe missing-data handling or the population used for analysis, it is not possible to determine how the available outcome observations relate to all enrolled or randomized participants.

Finally, the record identifies two pairwise primary comparisons and a secondary outcome but does not report a multiplicity strategy. In a study with several comparisons, the interpretation of individual p-values depends in part on how testing was planned and handled. The missing statistical details are not merely technical: they define what can be inferred from the posted results and what remains uncertain.

16. 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.

Several trial-specific limitations constrain interpretation. The registry marks the study terminated but does not state the reason, timing, or consequences for enrollment and follow-up. The registry enrollment is 22, while the arm descriptions state counts of 40, 40, and 20 and the primary-outcome summaries report 4, 8, and 10. The record does not explain these differences, so the intended and analyzed populations cannot be reconstructed from the posted information.

The primary endpoint description says that mean change and a 95% confidence interval are based on least-squares means from analysis of covariance. The posted results do not include those estimates or intervals. Instead, they provide arm means and standard deviations, along with Wilcoxon (Mann-Whitney) p-values for two pairwise comparisons. The record does not explain the relation between the stated ANCOVA method and these reported tests.

Details needed to assess the analyses are not reported in the registry record: the analysis population, covariates, missing-data methods, multiplicity approach, and the change-score convention. The record also does not give a clinical-importance threshold or explain the listed serious adverse-event terms by group. The secondary outcome is named but its numerical results are not part of the registry entries.

These limitations make it difficult to assess precision, potential bias from missing observations, consistency with the intended analysis, or the breadth of outcome reporting. They do not establish that the analyses were inappropriate; they identify information that the registry record does not report.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC) — NCT01716039.
• Registry record last updated 2021-06-23; status last verified 2021-06.
• Results first posted 2021-06-23.
• 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.

20. Record Summary

NCT01716039 is a phase 2 randomized, triple-masked, parallel-group study sponsored by Alimentiv Inc. It is marked terminated. The registry describes adalimumab with weekly oral methotrexate at 12.5 mg or 25 mg, compared with adalimumab and oral placebo, in people with moderately to severely active ulcerative colitis.

The primary outcome is change in modified Baron score from baseline to Week 18. Posted group mean changes are 0.7, 1.1, and 0.9 for placebo, MTX 12.5mg, and MTX 25 mg, respectively. Sponsor-reported Wilcoxon comparisons have p-values of 0.758 and 1.00. Between-group estimates and confidence intervals are not reported in the registry record.

Participant-count discrepancies, missing analysis details, and the absence of a reported multiplicity or missing-data plan limit interpretation. The record does not explain the study’s termination.