ACTH Gel Therapy in Rheumatoid Arthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ACTH Gel Therapy in Rheumatoid Arthritis (NCT02030028), a na na study. The primary outcome is Changes in Clinical Disease Activity Index (CDAI) Between Week 0 and Week 12.

2. Clinical Question

3. Trial Design

This was a completed, open-label, single-group study of ACTHAR Gel in people with rheumatoid arthritis. The registry lists an enrollment of 18. It records no allocation procedure and no masking, and there was no control group. As a result, the study was not designed as a randomized comparison between ACTHAR Gel and another treatment or control condition.

The recorded regimen was ACTH Gel for 12 weeks, at 80u (1mL) subcutaneously twice each week. The brief summary describes the intended participants as people already taking medications prescribed by their physician who continued to experience disease symptoms. The registry lists rheumatoid arthritis as the condition. It does not report further eligibility criteria or the background medications participants used.

The registry lists the phase as NA. The study start is recorded as 2014-11, primary completion as 2022-06-30, and status as completed. Those dates describe the registry timeline; they do not establish how long an individual participant was followed beyond the stated 12-week treatment period.

The primary outcome was a CDAI improvement threshold between week 0 and week 12. Secondary outcomes concerned DAS28-CRP, CRP, ESR, and patient-reported fatigue over the same period. A single-group design can describe change among participants with outcome data, but it does not separate change associated with the intervention from change that might occur for other reasons. The registry record does not report a study-specific sample-size justification, interim-analysis plan, or detailed statistical analysis plan.

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: No patients were excluded from the study based on enrollment criteria. Because ACTHAR administration was add on therapy, no wash out period was required.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Study completers (9/13 had evaluable data at baseline and week 12)

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 Changes in Clinical Disease Activity Index (CDAI) Between Week 0 and Week 12, measured over 12 weeks.

The primary endpoint is the number or proportion of participants achieving >20% improvement in CDAI after 12 weeks of therapy. The registry defines the improvement criterion by comparing CDAI at week 12 with CDAI at week 0: a week 12-to-week 0 ratio < 0.8 meets the criterion. The endpoint description notes that lower CDAI scores represent lower disease activity.

This is a binary outcome at the participant level: each participant either meets the stated threshold or does not. A threshold can make a clinical outcome easier to summarize as the share of participants meeting a prespecified degree of change. It also simplifies a range of possible score changes into two categories, so it does not show how large the changes were among participants who met the threshold or how close other participants came to it.

The endpoint is labeled as a change in CDAI between week 0 and week 12, but its stated measure is the count or percentage meeting the improvement criterion. The outcome population is described as study completers, with 9/13 having evaluable data at both baseline and week 12. The registry record does not report the number who met the criterion, the corresponding percentage, or an uncertainty interval. Without those results, the endpoint definition can be explained, but the observed degree of improvement cannot be quantified from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level measure. The registry defines the event as achieving >20% improvement in CDAI from baseline to week 12, operationalized as a ratio of week 12 CDAI to week 0 CDAI < 0.8. A binary endpoint reduces each participant's outcome to whether the criterion was met. The count of participants meeting it and the proportion meeting it are common descriptive summaries for this kind of endpoint. The registry record does not report either summary for the primary endpoint.

What does the threshold capture?

The threshold represents a specified amount of relative change, rather than a comparison of average CDAI scores. The registry states that lower CDAI scores represent lower disease activity. A participant whose ratio meets the stated criterion is counted as achieving the endpoint; the endpoint does not otherwise describe the size of that participant's change. A participant who does not meet the threshold is grouped with all other non-achievers, even though their individual score trajectories could differ. This is a general feature of threshold-based outcomes.

What can a single-group result estimate?

In a single-group study, a descriptive proportion can report how many observed participants met an outcome definition within the study group. It does not estimate a difference from an untreated or alternative-treatment group, because no such comparator is recorded. General statistical interpretation distinguishes a within-group change from a comparative treatment effect: the former describes observed change, while the latter requires a valid comparison and its assumptions. The registry records no randomized allocation and no control arm.

Open-label status means the study is recorded as having no masking. In general, knowledge of treatment assignment can affect reporting or assessment, especially for outcomes involving judgment or participant report. This is a design consideration, not evidence that such effects occurred in this study. The registry record does not report procedures intended to address this possibility.

How should uncertainty be understood?

A point estimate, such as a proportion meeting the threshold, summarizes the observed participants. A confidence interval, in general, gives a range of values compatible with the data under a statistical model and conveys sampling uncertainty. It does not remove possible bias from missing observations, an uncontrolled design, or measurement decisions. No primary-outcome estimate, confidence interval, or p-value is reported in the registry record, so neither the observed frequency nor its statistical precision can be assessed from the recorded information.

For a binary outcome, analyses may use methods suited to counts or proportions. The appropriate method depends on the analysis objective, the data, and the model assumptions. The registry record does not report which statistical test or model, if any, was used for the primary outcome. It also does not report an adjustment approach, a prespecified hypothesis-testing procedure, or a detailed analysis plan. Those methods cannot be inferred from the endpoint definition alone.

What does the planning illustration represent?

The planning material is expressly an illustration based on the observed effect, rather than a reconstruction of the study's own design calculation. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a fraction of the observed effect. This hypothetical two-arm framework is distinct from the recorded single-group design. The illustration should therefore be read as a planning exercise under its assumptions, not as a report of the study's actual enrollment rationale or as observed power. The registry record does not report the original sample-size justification.

In general, a sample-size calculation estimates how many participants would be needed to detect a specified effect under chosen assumptions. It depends on the outcome, target effect, variability or event frequency, significance level, power target, allocation, and analysis method. A planning calculation is conditional on those choices and is not evidence that a study had a particular probability of detecting an effect after it was completed. No numerical planning result is stated in the registry information, and no such value is needed to interpret the absent primary outcome result.

Why do outcome populations matter?

The primary outcome description identifies study completers and notes that 9/13 had evaluable baseline and week 12 data. In general, an analysis restricted to participants with evaluable observations can differ from an analysis that accounts for all enrolled participants. The choice can matter if the availability of outcome data is related to participant outcomes or other characteristics. The registry record does not describe the reasons for unevaluable data or a missing-data method, so the potential effect of missingness cannot be quantified.

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("ACTHAR Gel")
n      <- c(9)
events <- c(8)
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  ACTHAR Gel  9  8  88.9  51.8  99.7  56.5  98.0  55.5  97.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and four secondary outcomes: changes in DAS28-CRP, CRP, ESR, and patient-reported fatigue between week 0 and week 12. Considering multiple outcomes can create a multiplicity issue when several statistical tests are used to make claims. In general, the more conclusions drawn from separate tests, the more important it is to know whether a testing strategy or adjustment was prespecified. The registry record does not report a multiplicity strategy or detailed statistical analysis plan.

The record lists five outcome measures and zero analyses. Numerical results for the primary and secondary outcomes are not reported in the registry information. The absence of an analysis entry does not establish that no analyses were performed; it means that analysis details and results are not reported in the registry record.

The primary outcome population is described as study completers, with 9/13 having evaluable CDAI data at baseline and week 12. The registry does not explain the difference between the completer group and the participants with evaluable paired data, give reasons for missing or unevaluable observations, or describe imputation or other missing-data handling. In general, missing-data methods rely on assumptions about why information is unavailable. Without the reasons and methods, it is not possible to assess whether the reported population represents all enrolled participants or how missingness might affect an estimate.

The registry record also does not report whether the primary outcome analysis included all participants who started treatment, only completers, or another analysis population beyond the stated outcome description. That distinction matters because the population analyzed defines the group to which a result applies.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

For ACTHAR Gel, the registry records 18 participants at risk for serious adverse events and 0 participants affected. It records 18 participants at risk for other adverse events and 1 participant affected. Deaths are recorded as 0. No top serious adverse-event terms are listed.

These are participant counts, not rates per unit of follow-up. The serious-event count describes what was recorded for the listed group; it does not establish that serious events are impossible or that no events occurred outside the registry's reporting definitions or observation period. The registry record does not provide further detail about event timing, duration, severity categories beyond the serious classification, or follow-up completeness.

The count of 1 under other adverse events should be read according to that registry category; the record does not list a term for it in the registry record analyzed. The counts also do not provide a comparison with another group, because this study had no comparator arm. Safety reporting can describe the events recorded during a study, but these counts alone do not establish a comparative safety profile or support a conclusion about treatment effects.

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

The registry describes a short-term, open-label study of ACTHAR Gel in a single group of people with rheumatoid arthritis. Its primary outcome was defined as achieving >20% improvement in CDAI at week 12 relative to week 0, using a ratio < 0.8. The registry record does not report how many participants achieved that endpoint or the corresponding percentage. As a result, the primary outcome's observed frequency cannot be stated from the recorded information.

The outcome population is described as study completers, with 9/13 having evaluable CDAI data at baseline and week 12. That detail indicates that paired outcome data were available for a subset of the stated completer group. The record does not explain the unavailable data or state how it was handled. Consequently, even a reported result for those with evaluable measurements would need to be interpreted with attention to who was included and why others did not contribute evaluable data.

The single-group design permits description of outcomes in the enrolled group but does not provide a concurrent control comparison. General statistical reasoning cautions that a before-and-after change can reflect factors other than the intervention, including background care or changes over time. This does not establish that any particular factor influenced the study outcomes; it explains why the design cannot isolate an intervention effect as a randomized comparison would aim to do.

The record lists no inferential analysis results and no numerical primary estimate or confidence interval. Therefore, the size and precision of any observed change cannot be assessed from the registry information. The secondary outcomes are named, but their results are not reported in the record examined.

The safety figures record 0 participants affected by serious adverse events among 18 at risk, 1 affected by other adverse events among 18 at risk, and 0 deaths. These counts describe the recorded events and are not comparative estimates. Taken together, the registry information supports a description of the study design, outcome definition, evaluable-data note, and recorded safety counts. It does not support a conclusion about the primary endpoint's frequency, comparative benefit, or comparative risk.

14. Why This Trial Matters Statistically

This study illustrates why an outcome definition and an outcome result are not interchangeable. The registry specifies a clear participant-level CDAI threshold: >20% improvement over 12 weeks, defined by a week 12-to-week 0 ratio < 0.8. But it does not report the number of participants meeting that threshold. Knowing the rule makes the endpoint interpretable; it does not reveal the observed result.

It also illustrates how design determines what a result could mean. A single-group, open-label study can describe outcomes during a treatment period, but it lacks a concurrent comparator for estimating a difference between treatment strategies. This distinction matters even when an outcome is measured consistently: measurement detail cannot replace a comparison group when the question concerns comparative effects.

The evaluable-data note is another important statistical detail. The record describes study completers and says 9/13 had evaluable baseline and week 12 data. Readers need information about analysis populations and missing observations to understand who contributed to an endpoint estimate. Here, the reasons for unevaluable data and the handling of missing observations are not reported in the registry record.

Finally, planning calculations need to be separated from what a completed study observed. The planning material is described as an illustration using assumptions for a hypothetical two-arm calculation; it is not the study's own design justification or observed power. Keeping those concepts distinct helps prevent a planning exercise from being mistaken for evidence about the study's results. These issues are central to reading registry results carefully, particularly when a design, endpoint definition, and outcome values are not all reported with the same level of detail.

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 the primary endpoint is that its result is not reported in the registry record. The endpoint is defined, but the number meeting the criterion, the proportion, and an uncertainty interval are absent from the information analyzed. This prevents assessment of the observed frequency and its precision.

The single-group design has no comparator arm, and the study is open label. It therefore does not provide a randomized, masked comparison with which to distinguish outcomes during treatment from outcomes under another condition. This limits causal and comparative interpretation independently of the missing numerical endpoint result.

The outcome population is described as study completers, with 9/13 having evaluable data at baseline and week 12. The registry record does not explain the unevaluable observations or describe how missing data were handled. It also does not report further detail on the analysis population, eligibility criteria, background medication use, or outcome assessment procedures.

The record lists secondary outcomes but does not report their numerical results or analysis details. It does not report the statistical analysis plan, multiplicity handling, interim analyses, or the study's sample-size justification. Those omissions limit assessment of how outcomes and statistical tests were planned and interpreted. The sample-size material is described as a planning illustration, not as the original design rationale.

The registry records safety counts, but not detailed event descriptions or a comparator group. The counts therefore offer limited context for interpreting the frequency or nature of events and cannot be used to estimate comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: ACTH Gel Therapy in Rheumatoid Arthritis — NCT02030028.
• Registry record last updated 2023-09-06; status last verified 2023-08.
• Results first posted 2023-09-06.
• 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

The registry record describes a completed, open-label, single-group study of ACTHAR Gel for rheumatoid arthritis, with enrollment of 18. The recorded regimen was 80u (1mL) subcutaneously twice each week for 12 weeks. The primary outcome was >20% improvement in CDAI between week 0 and week 12, defined as a week 12-to-week 0 ratio < 0.8.

The primary outcome population is described as study completers; 9/13 had evaluable data at baseline and week 12. The registry record does not report the number meeting the primary criterion, an inferential analysis result, or details of missing-data handling. Secondary outcomes concern DAS28-CRP, CRP, ESR, and fatigue.

Safety counts record 0 participants with serious adverse events, 1 with other adverse events, and 0 deaths. No comparator was recorded, so the study does not provide a direct treatment comparison.