Treatment Of Knee Osteoarthritis With Intra-Articular Infliximab: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment Of Knee Osteoarthritis With Intra-Articular Infliximab (NCT01144143), a randomized phase 4 study. The primary outcome is Change in Cellular Infiltrates From Day 0 to Day 28.

2. Clinical Question

The study’s central biological question concerns cellular infiltration in the knee. Inflammation was also part of the study’s broader rationale: the summary says the investigators wanted to determine whether infliximab would reduce synovial-lining inflammation and help assess synovial fluid accumulation and cartilage breakdown. Those aims describe what the study set out to examine, not what its results demonstrated.

The registry lists changes in joint effusions, WOMAC score, serum IL-6, serum CRP, and serum SAA among the secondary outcomes. These measures address joint findings, symptoms or function, and circulating inflammatory markers. The record does not provide estimates for these outcomes, so the extent or direction of any changes cannot be described.

The primary endpoint is recorded as a count of participants, with cellular infiltration scored from 0 to 3. That format raises an important interpretation question: the score is ordinal, while the listed unit is participants. The registry record does not explain how scores were summarized or how changes between study visits were compared. Accordingly, the intended comparison can be stated, but its numerical result and analytical meaning cannot be established from the record.

3. Trial Design

The registry identifies this as a completed, Phase 4, randomized, double-blind, parallel study. Its official title describes it as single center, randomized, double-blind, and placebo-controlled. The stated enrollment is 16. The record gives a start date of 2007-07 and a primary completion date of 2010-12.

The groups identified in the posted safety record are Infliximab, Salt Water, and Methylprednisolone Acetate. The intervention list also identifies placebo and describes methylprednisolone acetate as standard of care. The registry does not provide arm descriptions, and it does not report the treatment schedule, doses, or details of allocation. Although the study is described as randomized and double-blind, the record does not specify how the randomization sequence was generated or who was masked.

A parallel design generally assigns participants to a group and compares outcomes across groups, rather than having each participant receive every treatment. That is a general description of the design type, not a report of the trial’s specific procedures. The registry identifies the design as parallel but does not provide further operational details.

The primary outcome concerns change in cellular infiltrates from Day 0 to Day 28. The stated timeframe is Day 0 to Day 28, and the outcome description says cellular infiltration was scored from 0 to 3. The registry also lists secondary measures involving joint effusions, WOMAC score, and serum markers, with some specified from Day 0 to Day 56. Results for those outcomes are not reported in the registry record.

The study status is completed, but completion status alone does not convey what the outcomes showed. The registry record does not report the primary outcome results, group comparisons, confidence intervals, p-values, or a statistical analysis plan. It also does not explain the sample-size justification for the trial’s enrollment.

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: In the MPA arm, one subject was excluded from the analysis because their biopsy sample was of insufficient quantity to be processed in the lab.

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 Cellular Infiltrates From Day 0 to Day 28, measured over Day 0 to Day 28.

The primary endpoint is titled Change in Cellular Infiltrates From Day 0 to Day 28. Its description says cellular infiltration was scored from 0 to 3, and its unit is listed as participants. The outcome is intended to capture a change in cells present in the sampled tissue over the specified period. In the study’s stated rationale, inflammation in the synovial lining is a central biological concern, making cellular infiltration relevant to the question being investigated.

In general, an endpoint is a defined measure used to assess a study question. A tissue-based measure can address a biological process directly, while measures such as symptoms or joint effusions describe other aspects of a condition. The registry lists WOMAC score and joint effusions as secondary outcomes, but does not provide results for them or explain how they relate analytically to the primary measure.

A score running from 0 to 3 has ordered categories, but the registry does not describe the category definitions beyond that range. It also does not explain whether investigators analyzed the score itself, categorized participants by change, or used another summary. The one stated population detail is that one subject in the MPA arm was excluded because the biopsy sample was insufficient in quantity to be processed in the lab. The registry record does not report the remaining participants’ scores, group summaries, or the primary comparison. Thus, the endpoint and its intended timing are identifiable, but the observed change is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary measure represent? The outcome is change in cellular infiltrates from Day 0 to Day 28. The registry describes cellular infiltration as scored from 0 to 3 and lists participants as the unit. In general, a score with ordered categories indicates rank or severity ordering, but the distance between neighboring categories need not have a consistent quantitative meaning. The registry does not define the categories or state how scores were converted into a measure of change. It also does not report the statistical method used for this endpoint.

Why does the outcome format matter? Statistical methods depend on the type of data and the question being asked. A continuous measurement, a count, a binary outcome, and an ordinal score have different properties. For an ordinal score, an analysis may preserve the ordering rather than treating category steps as equal intervals. That is a general methodological point, not a claim about the method used in this study. The registry lists the endpoint as a count of participants while also describing a 0-to-3 score; it does not explain the intended summary or resolve how those formats were combined.

What does randomization contribute? In general, random assignment is intended to make treatment groups comparable, on average, with respect to factors that might otherwise influence outcomes. The registry identifies the trial as randomized, but does not report sequence generation, allocation concealment, or details of implementation. Double masking is also identified, but the record does not state which people were masked or how masking was maintained. These omissions prevent a detailed assessment of the procedures from the registry entry alone.

How should an estimate and its uncertainty be read? In general, an effect estimate describes the observed difference or change on a chosen scale. A confidence interval gives a range of values compatible with the data and the method’s assumptions, conveying precision as well as direction. A wide interval indicates greater uncertainty than a narrow interval. A p-value addresses compatibility with a specified statistical model and null hypothesis; it does not measure clinical importance or the probability that a treatment works. The registry record provides no primary effect estimate, confidence interval, or p-value, so those interpretations cannot be applied to the study’s primary result.

What does the planning illustration mean? The registry’s stated sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design justification. The assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set as a stated fraction of the observed effect. Participant requirements are described per arm except for time-to-event calculations, which use total events. The numerical planning requirements are not reported in the registry record. These assumptions should not be read as proof that the trial had adequate power, and sample-size illustrations are not observed power.

The described planning assumptions also use an equal-allocation comparison between two arms, while the safety record identifies three groups. The registry record does not explain how the planning illustration relates to the trial’s group structure or which effect estimate was used. It does not report a protocol-based sample-size justification. In general, planning calculations depend on assumptions about the outcome, target effect, variability, significance level, allocation, and chosen power. If those assumptions differ from the eventual study conditions, the resulting planning figure may not describe the precision obtained.

Why can outcome distributions matter? General statistical methods make assumptions about the form and variability of observed data. For count outcomes, for example, a model may assume a particular relationship between the mean and variance. Over-dispersion means the observed variability exceeds what a chosen model expects; if it is ignored, uncertainty can be understated. That concept is general. The primary endpoint is described using a score and a participant unit, and the registry does not report a model, a distribution, or an assessment of over-dispersion.

What can the safety counts tell us? Counts of participants affected are direct descriptive summaries. In general, comparative interpretation also depends on the denominator, the type and timing of events, and uncertainty around the rates or contrasts. The registry provides numbers at risk and numbers with other adverse events, but does not list the event terms in the record’s safety summary. For serious adverse events, it reports zero affected in each group. The counts do not establish that risks are identical, especially when the groups are small, and the registry does not provide a formal comparison.

How should analyses across outcomes be considered? When several outcomes are examined, the chance of observing a seemingly notable result can increase if no adjustment or hierarchy is used. In general, multiplicity procedures can control error across specified comparisons, but the choice depends on the study questions and analysis plan. The registry lists six outcome measures and records zero analyses. It does not report a testing hierarchy, multiplicity adjustment, model specifications, or analysis plan. Therefore, no particular approach should be attributed to the investigators.

The registry notes that one participant in the MPA arm was excluded from the primary analysis because the biopsy sample was insufficient to process in the lab. In general, missing or unusable endpoint data can change the analyzed population and reduce precision. Interpretation depends on the reasons for missingness and the method used to address it. The record does not report whether other participants had missing data, whether imputation was used, or how the exclusion affected the analysis. The general concepts above explain what statistical details would matter; they do not identify methods actually used in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures. The primary measure is change in cellular infiltrates from Day 0 to Day 28; the listed secondary outcomes include joint effusions, WOMAC score, and serum IL-6, CRP, and SAA. Multiple outcomes can create multiplicity concerns when many hypotheses are tested. In general, a prespecified outcome hierarchy or adjustment method can help control the interpretation of multiple tests. The registry record does not report a hierarchy, multiplicity adjustment, or statistical analysis plan.

The record lists zero analyses. It does not provide outcome estimates, inferential tests, or a description of models. The multiplicity implications of the actual analyses therefore cannot be assessed. The six outcome measures alone do not establish that six separate statistical tests were performed.

For the primary outcome, the registry states that one subject in the MPA arm was excluded because the biopsy sample was of insufficient quantity to be processed in the lab. It does not report how many participants contributed usable primary data in the other groups, whether other data were missing, or how the exclusion was incorporated into the analysis. It also does not describe an intention-to-treat or per-protocol population, or any imputation or sensitivity analysis. Those details are not reported in the registry record.

In general, missing-data handling is important because the reason data are unavailable may be related to the outcome, and different approaches can yield different estimates. The stated biopsy exclusion is a specific limitation of the recorded primary population, but the record does not contain enough information to judge its effect on the result. No analysis population or missing-data method should be inferred.

11. 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 non-serious adverse event terms

The registry reports serious adverse events for three groups. Infliximab had 0 serious adverse events among 8 at risk; Salt Water had 0 among 4 at risk; and Methylprednisolone Acetate had 0 among 4 at risk. Deaths are not reported in the registry record.

For other adverse events, 4 of 8 participants were affected in the Infliximab group, 1 of 4 in the Salt Water group, and 2 of 4 in the Methylprednisolone Acetate group. These are descriptive counts, not adjusted comparisons. The registry does not provide event terms in the listed safety summary, timing, severity details for these other events, or uncertainty estimates for differences between groups.

In general, an observed count is not a precise estimate of the underlying risk, particularly when the number at risk is small. Zero reported serious events means none were recorded in these groups in the registry summary; it does not establish that the true risk is zero. The record’s serious-event figures should be read as limited descriptive safety information, not as evidence that groups have equivalent safety profiles.

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

The registry record identifies a completed, randomized, double-blind study of intra-articular infliximab for knee osteoarthritis, with Salt Water and methylprednisolone acetate groups also identified in the safety record. It defines the primary outcome as change in cellular infiltrates from Day 0 to Day 28 and describes cellular infiltration as a score from 0 to 3. This information establishes the study’s intended measurement and broad design, but not the result.

The primary outcome values and group comparisons are not reported in the registry record. Neither the direction nor the size of a change can be described, and there is no reported interval or p-value to indicate statistical precision. The registry also lists secondary measures, but their results are not reported. Consequently, the record does not establish whether any group differed from another on the primary or secondary outcomes.

The safety figures describe serious and other adverse events among the listed numbers at risk. They are useful as a record of what was reported, but do not constitute a complete comparative safety analysis. Small group counts and absent uncertainty estimates leave substantial limits on interpretation. Deaths are not reported in the registry record.

In general, a study result must be interpreted in light of its endpoint definition, analysis methods, missing data, and uncertainty. Here, one MPA-arm participant was excluded from the primary analysis because the biopsy sample was insufficient for laboratory processing, while the handling of that exclusion and any other missing data is not reported. The analysis plan and primary statistical analysis are also not reported.

The study’s stated purpose was to examine inflammation and related outcomes. Purpose is not evidence of an observed effect. Without the posted outcome results, no conclusion about the relative effects of the study groups follows from the information in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because it asks a biological question using a tissue-based primary endpoint while also listing joint, symptom-related, and serum-marker outcomes. The primary endpoint is cellular infiltration scored from 0 to 3, but the registry does not define the score categories or specify how the score was summarized. Clear endpoint definitions and analysis methods are important for understanding what a reported change represents.

The record identifies randomization, double masking, and a parallel design. These features are relevant to interpretation, but their labels do not replace details about implementation. The registry does not report how allocation was generated, who was masked, or how the primary endpoint was analyzed. Such information helps readers assess the potential for bias and understand the comparison being estimated.

The stated enrollment is 16, and the safety record identifies groups with 8, 4, and 4 participants at risk. The primary analysis also excluded one MPA-arm subject because the biopsy sample was insufficient for laboratory processing. These features make precision and analysis-population details especially important. Yet the record does not report primary estimates, uncertainty intervals, or the handling of missing data.

Six outcome measures are recorded, while zero analyses are listed. This distinction matters: an outcome list shows what was to be measured, not what was analyzed or found. Without analysis results or a multiplicity plan, readers cannot judge the consistency of findings across measures or the uncertainty around any comparison.

The record therefore illustrates a broader statistical principle: trial design labels and outcome definitions are not enough to interpret effectiveness or comparative safety. Numerical results, uncertainty, analysis methods, and transparent handling of missing data are needed. The registry entry supplies some design and safety information, but does not report the primary outcome analysis.

14. 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 most consequential limitation of the registry record is that it does not report the primary outcome results. The endpoint is defined as change in cellular infiltrates from Day 0 to Day 28, with a score from 0 to 3, but no group summaries or comparative estimates are present. No confidence interval or p-value is reported, so neither effect magnitude nor precision can be assessed.

The record does not describe the score categories, the method used to summarize the ordinal score, or the statistical model. It lists participants as the unit while describing an individual score, without clarifying the analysis format. The analysis plan and protocol-based sample-size justification are not reported in the registry record.

One participant in the MPA arm was excluded from the primary analysis because the biopsy sample was insufficient to process in the lab. The registry does not report the size of the analyzed primary-outcome population by group, whether there were other missing observations, or how the exclusion was handled. The analysis population and any sensitivity analyses are not reported.

Although the study is described as randomized and double-blind, the registry does not report the randomization procedure, allocation concealment, or who was masked. Arm descriptions and treatment schedules are also not reported. The record identifies a single-center study, but does not provide details that would support evaluation of how broadly the findings might apply.

The safety summary provides counts but no event descriptions for other adverse events, no uncertainty estimates, and no reported death figures. The listed outcomes and absence of analyses also leave multiplicity and selective reporting difficult to assess. These limitations concern what is available in the registry record and do not establish what was or was not reported elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment Of Knee Osteoarthritis With Intra-Articular Infliximab — NCT01144143.
• Registry record last updated 2018-02-08; status last verified 2018-01.
• Results first posted 2018-02-08.
• 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.

18. Record Summary

The registry describes a completed, Phase 4, randomized, double-blind, parallel study titled Treatment Of Knee Osteoarthritis With Intra-Articular Infliximab. The official title identifies it as single center and placebo-controlled. Enrollment is 16; the recorded start is 2007-07 and primary completion is 2010-12. Herbert Lindsley, MD is listed as sponsor.

The primary outcome is change in cellular infiltrates from Day 0 to Day 28, with cellular infiltration scored from 0 to 3. The record lists secondary outcomes involving joint effusions, WOMAC score, and serum IL-6, CRP, and SAA. It identifies Infliximab, Salt Water, and Methylprednisolone Acetate groups in the safety record.

Safety counts include zero serious adverse events in each group and other adverse events affecting 4 of 8, 1 of 4, and 2 of 4 participants, respectively. One MPA-arm subject was excluded from the primary analysis because the biopsy sample was insufficient for laboratory processing. Primary outcome results, statistical analyses, and the analysis plan are not reported in the registry record.