A Study To Investigate And Describe The Treatment Patterns And Effect Of Tofacitinib Indicators For Patients With Rheumatoid Arthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study To Investigate And Describe The Treatment Patterns And Effect Of Tofacitinib Indicators For Patients With Rheumatoid Arthritis (NCT04721808), a registered phase not stated study. The primary outcome is Percentage of Participants Who Achieved Low Disease Activity (LDA) (Clinical Disease Activity Index [CDAI] <=10) at 6 Months: by Overall Tofa Initiators, Monotherapy and Combination Therapy Initiators.

2. Clinical Question

The study also describes treatment patterns and several six- and twelve-month outcomes, including remission, changes in disease activity and patient-reported measures, and modified American College of Rheumatology response categories. Those outcomes are listed for overall initiators and, where specified, for monotherapy and combination therapy initiators. Numerical results for these outcomes are not reported in the registry record.

This is a question about observed outcomes among registry participants receiving tofacitinib, not a randomized estimate comparing tofacitinib with another treatment. The record does not identify a control group or state an allocation method. Consequently, the primary question is descriptive: it concerns the observed proportion meeting a disease-activity threshold in the eligible registry population. It does not by itself estimate what would have happened to the same participants under another treatment.

3. Trial Design

The study is titled “Treatment Patterns and 6 and 12-Month Effectiveness of Tofacitinib in the Corrona Rheumatoid Arthritis Registry.” It concerns rheumatoid arthritis and uses real-world patient data entered in the Corrona Rheumatoid Arthritis Registry on or after November 2012. The record describes people receiving tofacitinib, with the main outcome population restricted to eligible initiators with six months of follow-up.

The registry record lists an enrollment of 1712. It gives a study start date of 2021-01-22 and a primary completion date of 2021-11-24, and the status is completed. The primary outcome timeframe says that the measure is assessed at six months after tofacitinib initiation, using data retrieved and observed for approximately 10 months of this retrospective study. These study dates do not, on their own, specify the observation period for every participant.

The primary outcome is presented for overall tofacitinib initiators and separately for monotherapy and combination therapy initiators. Combination therapy is described as tofacitinib with methotrexate, arava, azulfidine, plaquenil, or cyclosporine. These categories describe treatment at initiation; the registry record does not establish that participants were assigned to a treatment group by randomization.

No separate control treatment is identified, and allocation is not stated. The record therefore does not describe a randomized, like-for-like comparison between treatment groups. It does not report the eligibility criteria in full, the number analyzed for the primary outcome, or a detailed account of how follow-up and treatment exposure were handled. Numerical primary and secondary outcome results 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Analysis population included all eligible participants who initiated tofacitinib on or after November 2012 and had 6 months follow-up. Here, "Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and "Number Analyzed" signifies number of participants evaluable for specified category.

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: Analysis population included all eligible participants enrolled in Corrona RA registry who initiated tofacitinib on or after 06-Nov-2012 and had at least 6-month follow-up visit before 31-Jan-2021.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Achieved Low Disease Activity (LDA) (Clinical Disease Activity Index [CDAI] <=10) at 6 Months: by Overall Tofa Initiators, Monotherapy and Combination Therapy Initiators, measured over At 6 months after initiation of tofacitinib (from the data retrieved and observed for approximately 10 months of this retrospective study).

The primary endpoint is the percentage of participants who achieved low disease activity at six months after initiating tofacitinib. Low disease activity is defined as a Clinical Disease Activity Index (CDAI) score of 10 or less. The registry record describes the outcome separately for overall initiators, monotherapy initiators, and combination therapy initiators.

CDAI is a composite measure formed from tender joint count and swollen joint count, each assessed across 28 joints, together with patient and physician global assessments of disease activity. The global assessments use visual analog scales from 0 to 100 millimeters. The CDAI total score ranges from 0 to 76, with lower scores representing lower disease activity. The record classifies scores above 10 and up to 22 as moderate disease activity and scores above 22 as high disease activity.

A threshold-based endpoint gives a readily interpretable summary: it counts participants whose measured disease activity falls within the stated low-activity category at the assessment time. It is different from reporting the average score or average change, because it reduces the score to whether each participant is on one side of the cutoff. That can make a percentage easy to communicate, but it also means that participants with scores close to the cutoff may be placed in different categories despite similar measurements. These are general properties of threshold outcomes, not additional findings from this study.

The registry record specifies a 95% confidence interval for the percentage, but does not report the observed percentage or its interval. The exact number of participants evaluated for this endpoint is also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of estimate does the primary outcome represent?

The primary measure is a percentage: the number of eligible participants meeting the low disease activity definition divided by the number assessed for that endpoint, expressed as a proportion of the analyzed group. This is a general description of how a binary percentage is constructed. The registry record does not state the actual numerator or denominator, so neither can be recovered from the information recorded.

The outcome is binary for each participant at the six-month assessment: CDAI is either 10 or less, meeting the low disease activity definition, or it is above that threshold. Summarizing a binary outcome as a percentage retains the count meeting the criterion relative to the number assessed, but it does not show how far individual CDAI scores are from the threshold. A participant just above the cutoff and a participant with a much higher score both fall outside the low disease activity category.

How should a confidence interval be read?

The registry record specifies a 95% confidence interval for the primary percentage. In general, a confidence interval conveys the statistical uncertainty associated with an estimate under a particular method and its assumptions. It is not a guarantee that the true value lies in the interval, and it does not address every source of uncertainty. For example, an interval around a percentage does not by itself correct for selection into a registry, missing follow-up, confounding, or measurement error.

The record does not provide the interval limits or state how the interval was calculated. Different methods can be used for a proportion, and their behavior can vary with the amount of information and the observed proportion. No specific interval method should therefore be attributed to this study. Without the estimate, interval, and analysis denominator, the precision of the primary result cannot be assessed.

What do the treatment-pattern groups represent?

The primary outcome is specified for overall tofacitinib initiators and for the monotherapy and combination therapy categories. The combination category includes tofacitinib with methotrexate, arava, azulfidine, plaquenil, or cyclosporine. These are descriptive treatment-pattern groups. In general, observed differences between such groups can reflect differences in the participants or their care as well as differences associated with treatment pattern. A randomized assignment process could help balance measured and unmeasured characteristics on average, but random allocation is not described in this record.

Separate estimates for subgroups also typically have fewer contributing observations than an estimate for a combined population, and their confidence intervals may consequently be less precise. This is a general statistical consideration, not a reported finding about this study: subgroup denominators and uncertainty intervals are not reported in the registry record. No adjustment method for comparisons between treatment-pattern groups is described.

What can be inferred from the listed sample-size assumptions?

The record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is specified as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustrations are expressed as participants per arm; time-to-event illustrations use a total event count. These are planning conventions, not evidence that the registry study used randomized arms or that it had a particular power.

No numerical planning estimates are included in the record, and the observed effect needed as an input is not reported. The illustrations therefore cannot be interpreted as an achieved sample size, an observed power calculation, or a justification for the study's enrollment. The registry record does not report a sample-size justification for the study's own design.

In general, power calculations describe the probability of detecting a specified effect under a set of assumptions if a study were conducted as planned. They are not a measure of how convincing an observed result is after the study. A post hoc calculation based on an observed estimate does not replace a confidence interval, and a planning illustration does not reveal whether the endpoint was measured completely or analyzed as intended.

Why might variation exceed a simple model's expectations?

General statistical note: when outcome variation is greater than a model assumes, standard errors can be too small and confidence intervals too narrow if the extra variation is ignored. This is often called over-dispersion. Whether that issue is relevant depends on the statistical model and data structure. The registry record does not report a model for the primary percentage, a dispersion assessment, or any adjustment for clustering, so no conclusion about over-dispersion can be made for this study.

For registry data more broadly, participants may differ in clinical characteristics, treatment histories, and follow-up. Appropriate handling of such variation depends on the analysis question and available data. The record does not describe a regression model, covariate adjustment, or a method for accounting for repeated observations. These methods must not be assumed solely because outcomes are reported at multiple timepoints.

What analysis details are absent?

The registry record does not report the statistical analysis plan, the method for calculating the confidence interval, any interim analyses, or how missing outcome measurements were handled. It also does not give the primary analysis denominator or the numbers contributing to each treatment-pattern group. These omissions prevent a fuller assessment of estimation, uncertainty, and potential bias. The definitions and timepoints identify what was intended to be measured, but they do not specify the statistical procedure used to produce an estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 48 outcome measures, including the primary six-month low disease activity percentage and multiple secondary measures at six and twelve months. The secondary outcomes include remission, changes in CDAI, HAQ, pain and fatigue visual analog scale scores, and modified ACR response categories. Many are described for overall initiators and for monotherapy and combination therapy initiators. The record does not report a multiplicity strategy, such as a prespecified hierarchy or adjustment of significance thresholds across outcomes.

General statistical note: examining many outcomes or subgroup estimates creates more opportunities for apparently notable findings to occur by chance. Multiplicity procedures can help control the chance of false-positive conclusions across a defined family of tests, but the appropriate approach depends on the study's aims. Because numerical results and a testing plan are not reported, it is not possible to assess how multiplicity was handled or whether any outcome was designated for confirmatory inference.

The record defines the primary outcome population as eligible participants who initiated tofacitinib on or after November 2012 and had six months of follow-up. It does not report how many met these conditions, how many were analyzed, or how missing CDAI measurements were handled. Missingness can affect a percentage if participants without an assessment differ from those with one. General methods for addressing missing data rely on assumptions; the registry record does not identify a method or its assumptions.

The analysis population for each secondary outcome, loss to follow-up, and any imputation or sensitivity analysis are not reported in the registry record. The presence of twelve-month outcomes does not establish that the same participants contributed at both timepoints. These gaps limit assessment of the representativeness and comparability of the reported populations.

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

If an observed primary percentage and confidence interval were available, they would describe how common the defined low disease activity status was among eligible participants assessed at six months, along with statistical uncertainty under the interval method. The registry record does not report those numerical results, so it cannot establish the observed frequency or how precisely it was estimated.

Even with a reported percentage, a registry cohort without a described randomized comparator would support a description of outcomes among participants receiving tofacitinib, not an unqualified causal attribution to the treatment. In general, treatment choices and participant characteristics in observational data may be related. A comparison of monotherapy and combination therapy initiators could therefore reflect differences in who received each treatment pattern, as well as any treatment-related differences. The registry record does not report an adjustment strategy that would address this concern.

The primary endpoint is a threshold classification of CDAI at one follow-up timepoint. It does not describe the entire course of disease activity, the amount of change from baseline, or outcomes outside the defined measure. Likewise, the listed secondary outcomes indicate measures intended for assessment but do not establish their observed values or patterns over time.

The record also lists zero counts in the serious-event fields for tofacitinib initiators and no top serious terms. These registry fields do not, by themselves, establish that no adverse events occurred; the record does not provide further information to interpret those entries. No conclusion about safety should be drawn from the zero entries alone.

In short, the registry record documents the study question and outcome definitions, but numerical outcome findings are not reported in the registry record. The study status of completed does not substitute for estimates, denominators, confidence intervals, or a description of analysis methods. The available information therefore supports understanding what the study set out to describe, not claims about the size, precision, or cause of any treatment-associated outcome.

12. Why This Trial Matters Statistically

This study addresses a statistical question that differs from a conventional randomized treatment comparison. It uses a rheumatoid arthritis registry to describe treatment patterns and outcomes among people initiating tofacitinib in routine care. Such work can characterize what outcomes are measured in a clinical registry and how findings are organized by treatment pattern, while requiring care in distinguishing descriptive estimates from causal comparisons.

The primary endpoint is a clinically interpretable category based on CDAI, with an explicit threshold for low disease activity. The definition makes the outcome understandable, while also illustrating a broader statistical tradeoff: thresholds simplify a continuous score into a category and can conceal variation within each category. The study also lists continuous change measures and response categories, providing a broader set of intended outcome descriptions.

Statistically, the record highlights why denominators and uncertainty matter. A percentage without the number analyzed or its confidence interval cannot show how stable or precise an estimate is. This is especially relevant when the intended summaries are divided into overall, monotherapy, and combination therapy groups. The registry record does not report those numerical details, so the planned descriptive comparisons cannot be evaluated.

The listed outcomes also raise familiar issues in real-world research: multiple measures and timepoints, incomplete follow-up, and differences between treatment groups. These issues require transparent analysis and missing-data methods if the aim extends beyond simple description. The registry record does not report those methods, so they cannot be assessed. The statistical importance of the study lies in the questions and measurement framework it identifies, alongside the need to distinguish recorded outcome definitions from reported evidence.

13. 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 primary limitation for interpretation is that numerical outcome estimates are not reported in the registry record. The primary percentage, its 95% confidence interval, and the number analyzed are absent. This prevents assessment of the observed outcome and its precision. Numerical results for the secondary outcomes are also not reported.

The record describes registry-based data and does not identify a separate control treatment or allocation method. It does not describe randomization, and the monotherapy and combination therapy categories should not be read as randomized arms. The record also does not report a statistical adjustment strategy for differences between those groups. As a result, it does not establish a causal effect or a fair treatment comparison.

Important analysis details are not reported in the registry record: full eligibility criteria, group-specific denominators, missing-data handling, the confidence-interval method, a statistical analysis plan, or interim analyses. The record lists 48 outcome measures but does not report a multiplicity strategy. These omissions limit evaluation of selection, follow-up, precision, and the interpretation of any outcome comparisons.

The study dates and the stated approximate observation period do not fully describe participant-level follow-up. The record also gives zero entries in the serious-event fields and no top serious terms, without enough detail to interpret those entries as evidence that no adverse events occurred. Finally, the record's completed status and enrollment figure do not resolve these gaps in outcome reporting or analysis detail.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: A Study To Investigate And Describe The Treatment Patterns And Effect Of Tofacitinib Indicators For Patients With Rheumatoid Arthritis — NCT04721808.
• Registry record last updated 2023-09-29; status last verified 2023-09.
• Results first posted 2023-09-29.
• 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.

17. Record Summary

The registry record describes a completed retrospective study of treatment patterns and six- and twelve-month outcomes among people with rheumatoid arthritis receiving tofacitinib in the Corrona Rheumatoid Arthritis Registry. Enrollment is listed as 1712. The study start date is 2021-01-22, and the primary completion date is 2021-11-24.

The primary endpoint is the percentage of eligible initiators with CDAI of 10 or less at six months, reported for overall initiators and by monotherapy or combination therapy. Combination therapy is defined as tofacitinib with methotrexate, arava, azulfidine, plaquenil, or cyclosporine. The record lists additional six- and twelve-month outcomes, but numerical outcome results, analyzed denominators, and key analysis methods are not reported in the registry record.