This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Efficacy of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Proliferative Lupus Nephritis (NCT02547922), a randomized phase 2 study. The primary outcome is Change From Baseline in 24-hour Urine Protein to Creatinine Ratio (UPCR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02547922 |
| Phase | Phase 2 |
| Condition | Lupus Nephritis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 147 |
| Arms in the primary outcome | 4 |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
Adults with active proliferative lupus nephritis were eligible for the study. The primary outcome population was the full analysis set: participants who received at least one dose and were analyzed according to randomized treatment, under a modified intention-to-treat principle. For this outcome, the number analyzed refers to participants with available data.
Intervention
The trial evaluated anifrolumab with standard of care, described as mycophenolate mofetil and corticosteroids. The registry lists a basic regimen and an intensified regimen, as well as an all-anifrolumab group. Further regimen details are not reported in the registry record.
Comparator
The comparator was placebo with standard of care. The placebo arm is described as placebo IV Q4W plus standard of care. The registry record does not provide further details about treatment duration or the administration schedule for the anifrolumab regimens.
Primary question
The primary endpoint was the geometric mean ratio of 24-hour urine protein-to-creatinine ratio at Week 52 over baseline. The trial evaluated anifrolumab plus standard of care against placebo plus standard of care. Values below 1 indicate improvement from baseline; the sponsor’s reported comparison combines the two anifrolumab regimens and compares them with placebo.
3. Trial Design
This was a randomized, parallel-group, phase 2 study in adults with active proliferative lupus nephritis. The registry lists quadruple masking and an overall enrollment of 147. It identifies three groups: anifrolumab basic regimen, anifrolumab intensified regimen, and placebo. The placebo arm is specified as placebo IV Q4W plus standard of care; standard of care is described as mycophenolate mofetil and corticosteroids.
The study was intended to evaluate the efficacy and safety of two anifrolumab doses compared with placebo. The primary outcome was change from baseline in 24-hour urine protein-to-creatinine ratio, expressed as the geometric mean ratio at Week 52 over baseline. The stated outcome timeframe runs from Week 1, identified as baseline, up to Week 52. A secondary outcome listed in the record was the proportion of participants achieving the composite endpoint complete renal response.
The registry reports a start date of 2015-11-04, a primary completion date of 2019-11-26, and completed status. These dates describe the registry record and do not, by themselves, indicate when individual participants were assessed or how long each participant was followed. More detail about the randomization procedure, concealment, masking roles, dose levels, treatment duration, and visit schedule is not reported in the registry record.
For the primary endpoint, the posted arm estimates include 41 participants in the basic-regimen group, 50 in the intensified-regimen group, 91 in the combined anifrolumab group, and 41 in the placebo group. These are outcome analysis counts, not the total enrollment. The outcome population is described as participants who received at least one dose and were analyzed according to randomized treatment, with the number analyzed reflecting those with available outcome data.
The reported sponsor comparison pools the anifrolumab regimens and contrasts the combined group with placebo. The separate basic and intensified group estimates are descriptive arm results; the reported mixed-model comparison is not a separate formal comparison of each regimen against placebo in the information available.
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: The screening period was from Day -30 to Day -1. Informed consent form (ICF) was signed prior to screening procedures. All the study assessments were performed as per the schedule of assessment.
Overall Study
| Stage | Anifrolumab - Basic Regimen | Anifrolumab - Intensified Regimen | Placebo |
|---|---|---|---|
| STARTED | 46 | 52 | 49 |
| FAS (Full Analysis Set) | 45 | 51 | 49 |
| COMPLETED | 18 | 28 | 20 |
| NOT COMPLETED | 28 | 24 | 29 |
Reasons for not completing this period:
| Reason | Anifrolumab - Basic Regimen | Anifrolumab - Intensified Regimen | Placebo |
|---|---|---|---|
| Withdrawal by Subject | 9 | 6 | 10 |
| Adverse Event | 3 | 1 | 2 |
| Lost to Follow-up | 1 | 0 | 0 |
| Lack of Efficacy | 5 | 7 | 4 |
| Death | 1 | 0 | 0 |
| Non-responding completer, Not eligible for extension study, Use of any restricted Medications | 4 | 8 | 9 |
| TECHNICAL PROBLEMS | 1 | 0 | 0 |
| PROGRESSIVE DISEASE | 1 | 0 | 2 |
| Physician Decision | 2 | 1 | 2 |
| Patients did not receive IP | 1 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS): The FAS included all subjects who received at least one dose of study treatment and were analyzed according to randomized treatment (mITT principle). Here, overall number of subjects analyzed signifies the subjects with available data that were analyzed for the outcome measure.
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: The full analysis set included all subjects who received at least one dose of study treatment and were analyzed according to randomized treatment.
| Characteristic | Unit | Anifrolumab - Basic Regimen | Anifrolumab - Intensified Regimen | Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 45 | 51 | 49 | 145 | |
| Age, Continuous | years | 35.2 (SD 11.49) | 35.0 (SD 10.58) | 34.0 (SD 10.18) | 34.7 (SD 10.68) |
| Sex: Female, Male: Female | Participants | 37 | 45 | 38 | 120 |
| Sex: Female, Male: Male | Participants | 8 | 6 | 11 | 25 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 22 | 23 | 20 | 65 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 23 | 28 | 29 | 80 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 3 | 1 | 0 | 4 |
| Race/Ethnicity, Customized: Asian | Participants | 11 | 7 | 10 | 28 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Black or African American | Participants | 2 | 4 | 1 | 7 |
| Race/Ethnicity, Customized: White | Participants | 17 | 25 | 24 | 66 |
| Race/Ethnicity, Customized: Other | Participants | 11 | 14 | 14 | 39 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in 24-hour Urine Protein to Creatinine Ratio (UPCR), measured over From Week 1 (Baseline) up to Week 52.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | milligram/milligram (mg/mg) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint concerns the 24-hour urine protein-to-creatinine ratio, or UPCR. It expresses urinary protein relative to urinary creatinine and is used as a measure of proteinuria in the setting of kidney disease. The registry defines the primary outcome as the geometric mean ratio of UPCR at Week 52 over baseline, in milligram/milligram (mg/mg). Values below 1 indicate improvement from baseline.
A ratio compares a follow-up measurement with its baseline reference. A value near 1 indicates little relative change on that ratio scale, while a value below 1 indicates a lower Week 52 UPCR relative to baseline. The geometric mean is used for outcomes that are analyzed on a multiplicative scale; it summarizes the central level after accounting for that scale, rather than reporting an arithmetic average of individual changes. This is a general explanation of the statistical measure, not a claim about the distribution of individual participants’ measurements.
The endpoint is clinically relevant to kidney involvement because it quantifies urinary protein, but it is a measurement outcome rather than the listed composite complete renal response endpoint. The registry does not establish that a particular UPCR ratio corresponds to a clinical benefit, nor does the posted primary outcome alone describe every aspect of kidney status. The full endpoint definition, including any handling of measurements outside the stated timeframe, is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
At Week 52, the geometric mean ratio estimates were 0.326 for the anifrolumab basic regimen, 0.285 for the intensified regimen, 0.305 for all anifrolumab, and 0.296 for placebo. Each estimate is a within-arm ratio of Week 52 UPCR over baseline. Since the registry states that values below 1 indicate improvement from baseline, all four posted arm estimates fall below 1. These separate arm summaries do not establish that one randomized group differs from another.
The corresponding 95% confidence intervals were 0.19 to 0.561 for the basic regimen, 0.177 to 0.457 for the intensified regimen, 0.198 to 0.468 for all anifrolumab, and 0.175 to 0.499 for placebo. A confidence interval conveys uncertainty around an estimate: narrower intervals indicate greater precision, while wider intervals indicate less precision. These intervals describe each arm estimate, not the uncertainty of a direct contrast between the individual regimen arms.
The sponsor’s reported mixed-model comparison combined all anifrolumab participants and compared them with placebo. It gives a geometric mean ratio of 1.031, with a 95% confidence interval from 0.621 to 1.713 and p = 0.905. This is a between-group comparison, distinct from the within-arm ratios above. The comparison interval includes 1, and the reported p-value does not indicate a clear statistical separation between the combined anifrolumab group and placebo under that model. The estimate and its interval also show substantial uncertainty about the size and direction of the contrast.
The arm-level point estimates should not be interpreted as proof of equivalence between groups: similar-looking point estimates do not establish that any difference is small enough to be clinically unimportant. Likewise, the data do not justify a conclusion about whether either regimen differs from placebo when analyzed separately, because such separate sponsor comparisons are not reported in the registry record.
The primary endpoint analysis is based on available outcome data among participants who received at least one dose and were analyzed by randomized treatment. The registry does not describe the amount or pattern of missing outcome data, or the assumptions used by the mixed model to handle it. Interpretation should therefore distinguish the posted estimates from a complete account of all randomized participants’ outcomes. The result is evidence about this specific measured endpoint and analysis, not a comprehensive summary of every efficacy or safety outcome in the study.
9. Statistical Methods Explained
What does the geometric mean ratio represent?
The endpoint is defined as the geometric mean ratio of 24-hour UPCR at Week 52 over baseline. A ratio puts follow-up and baseline on a relative scale. The registry explicitly states that values below 1 indicate improvement from baseline. For the individual arms, the posted ratios are 0.326, 0.285, 0.305, and 0.296. These are descriptive estimates for their respective groups. They do not, on their own, quantify the randomized contrast between treatment and control.
Geometric summaries are appropriate for quantities analyzed multiplicatively. In general, taking a geometric mean is related to averaging on a logarithmic scale and translating back to the original scale. This can be useful when relative changes are more meaningful than absolute changes. The registry does not give the raw UPCR measurements or enough detail to reconstruct individual participant changes.
How should the confidence intervals be read?
A confidence interval expresses the uncertainty associated with an estimate under the analysis method. The arm-specific 95% confidence intervals are 0.19 to 0.561, 0.177 to 0.457, 0.198 to 0.468, and 0.175 to 0.499. Their widths indicate that the estimates are not exact, and the interval endpoints show a range of values compatible with the data and method. These are not intervals for the treatment-versus-placebo effect; they belong to the separate arm estimates.
The sponsor’s model-based comparison has a geometric mean ratio of 1.031, with a 95% confidence interval from 0.621 to 1.713. For a ratio contrast, 1 represents no relative difference between the compared groups on that scale. The interval includes 1, so the posted comparison is compatible with values on either side of that reference. The interval is also broad, which indicates limited precision about the contrast’s magnitude. A confidence interval does not assign a probability to a particular treatment effect after the data have been observed.
What does the p-value add?
The sponsor reports p = 0.905 for the mixed-model comparison. A p-value measures how unusual data at least as incompatible with a specified null model would be, assuming that model and its assumptions. It is not the probability that the null hypothesis is true, nor is it a measure of the size or clinical importance of an effect. Read together with the estimate and interval, this value does not provide evidence of a clear difference in the reported combined-group comparison. It does not prove that the groups are equivalent.
Why does the model matter?
The registry names the sponsor’s method as mixed models analysis. In general, mixed models can analyze outcome data while representing relationships among repeated observations or other grouped measurements, depending on how the model is specified. Their estimates depend on the model terms, covariance structure, outcome transformations, and assumptions about missing data. Those implementation details are not reported in the registry record, so the model cannot be independently reconstructed from the posted summary.
The sponsor’s model-based contrast compares all anifrolumab with placebo. This combines participants from the basic and intensified regimens and differs from simply comparing the two separate arm summaries. General statistical principle: a formal contrast can incorporate model structure and may not equal a contrast calculated directly from the rounded arm estimates. No independent recalculated contrast is stated in the registry record, so the model-based estimate should be interpreted as the reported primary comparison rather than replaced with an improvised calculation.
What do planning illustrations mean?
Sample-size illustrations based on an observed effect are planning exercises, not observed power. In general, such calculations ask how many participants per arm might be needed under specified assumptions to detect a chosen fraction of an effect at a chosen significance level. The assumptions recorded for these illustrations are a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. These are not the trial’s own design justification. The registry record does not report the original sample-size justification, and an illustration based on the observed estimate cannot establish whether the study was adequately powered before it began.
General statistical principle: observed power, calculated from an observed result, adds little information beyond the estimate and confidence interval. The uncertainty interval is the more direct description of precision. The planning illustrations should therefore be understood as conditional scenarios, not as evidence that the study had a particular probability of detecting an effect.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Mixed Models Analysis | Geometric Mean Ratio 1.031 | 0.621 to 1.713 | 0.905 |
The registry reports a sponsor analysis using mixed models. It combines the anifrolumab basic and intensified regimens and compares all anifrolumab with placebo. The reported geometric mean ratio is 1.031, with a 95% confidence interval from 0.621 to 1.713 and p = 0.905. This is the primary between-group result to use when describing the sponsor’s analysis.
The separate arm estimates are not a substitute for that model-based comparison. They summarize Week 52 over baseline within each arm, and their rounded values cannot reproduce all features of a mixed-model contrast. The registry record does not report a separate sponsor model comparison for each anifrolumab regimen against placebo.
A recalculated unadjusted comparison is not reported in the registry record. The discrepancy indicator is false, so the record does not flag a disagreement between a recalculation and the sponsor’s result. If a recalculation were to differ from the sponsor analysis, the sponsor’s own analysis would take precedence when describing the reported trial result; no such discrepancy is flagged. The sponsor estimate should still be interpreted with its interval and the limitations in model and missing-data details, rather than as a definitive measure of clinical importance.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary endpoint: change from baseline in 24-hour UPCR, expressed as a geometric mean ratio at Week 52 over baseline. It also lists one secondary outcome, the proportion of participants achieving complete renal response. The record does not describe a multiplicity procedure, such as an adjustment to account for testing multiple outcomes or comparisons. Whether any such procedure was specified or used is not reported in the registry record.
The sponsor’s reported primary comparison combines the two anifrolumab regimens. The registry does not report separate inferential comparisons for each regimen against placebo in the posted primary analysis. It also does not report a testing hierarchy or explain how the secondary outcome relates to formal hypothesis testing. Without those details, the p-value should be understood as belonging to the stated mixed-model comparison, not as an across-outcomes or across-regimens error-controlled conclusion.
The primary outcome population is the full analysis set. It includes participants who received at least one dose of study treatment and were analyzed according to randomized treatment, described as a modified intention-to-treat principle. For this outcome, the overall number analyzed means participants with available data. The arm-specific counts for the outcome are 41, 50, 91, and 41 for the basic regimen, intensified regimen, all-anifrolumab group, and placebo, respectively.
The registry does not describe how many outcome measurements were missing, why measurements were unavailable, or whether missingness differed among groups. It does not report the model’s missing-data assumptions, any imputation strategy, sensitivity analyses, or the consequences of departures from those assumptions. These details matter because an analysis using available measurements may be affected if the availability of measurements is related to participants’ outcomes. The record also does not describe interim analyses, stopping rules, or a detailed statistical analysis plan. Those items are not reported in the registry record; their absence from the record does not establish whether they were or were not used.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Anifrolumab - Basic Regimen- Treatment Period | 10 | 45 | 22.2% |
| Anifrolumab - Intensified Regimen- Treatment Period | 9 | 51 | 17.6% |
| All Anifrolumab- Treatment Period | 19 | 96 | 19.8% |
| Placebo- Treatment Period | 8 | 49 | 16.3% |
| Anifrolumab - Basic Regimen- Follow up | 3 | 45 | 6.7% |
| Anifrolumab - Intensified Regimen- Follow up | 0 | 51 | 0.0% |
| All Anifrolumab- Follow up | 3 | 96 | 3.1% |
| Placebo- Follow up | 3 | 49 | 6.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Anifrolumab - Basic Regimen- Treatment Period | 0 of 45 |
| Anifrolumab - Intensified Regimen- Treatment Period | 0 of 51 |
| All Anifrolumab- Treatment Period | 0 of 96 |
| Placebo- Treatment Period | 0 of 49 |
| Anifrolumab - Basic Regimen- Follow up | 1 of 45 |
| Anifrolumab - Intensified Regimen- Follow up | 0 of 51 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Anifrolumab - Basic Regimen- Treatment Period | 31 of 45 |
| Anifrolumab - Intensified Regimen- Treatment Period | 39 of 51 |
| All Anifrolumab- Treatment Period | 70 of 96 |
| Placebo- Treatment Period | 33 of 49 |
| Anifrolumab - Basic Regimen- Follow up | 0 of 45 |
| Anifrolumab - Intensified Regimen- Follow up | 0 of 51 |
Most frequent serious adverse event terms
| Event term | Organ system | Anifrolumab - Basic Regimen- Treatment Period | Anifrolumab - Intensified Regimen- Treatment Period | All Anifrolumab- Treatment Period | Placebo- Treatment Period | Anifrolumab - Basic Regimen- Follow up | Anifrolumab - Intensified Regimen- Follow up |
|---|---|---|---|---|---|---|---|
| Herpes zoster | Infections and infestations | 3 of 45 | 3 of 51 | 6 of 96 | 0 of 49 | 0 of 45 | 0 of 51 |
| Lupus nephritis | Renal and urinary disorders | 1 of 45 | 1 of 51 | 2 of 96 | 1 of 49 | 1 of 45 | 0 of 51 |
| Influenza | Infections and infestations | 1 of 45 | 1 of 51 | 2 of 96 | 0 of 49 | 0 of 45 | 0 of 51 |
| Abscess bacterial | Infections and infestations | 1 of 45 | 0 of 51 | 1 of 96 | 0 of 49 | 0 of 45 | 0 of 51 |
| Pyelonephritis acute | Infections and infestations | 1 of 45 | 0 of 51 | 1 of 96 | 0 of 49 | 0 of 45 | 0 of 51 |
| Varicella zoster pneumonia | Infections and infestations | 0 of 45 | 1 of 51 | 1 of 96 | 0 of 49 | 0 of 45 | 0 of 51 |
| Endometrial adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 45 | 1 of 51 | 1 of 96 | 0 of 49 | 0 of 45 | 0 of 51 |
| Lupus endocarditis | Cardiac disorders | 1 of 45 | 0 of 51 | 1 of 96 | 0 of 49 | 0 of 45 | 0 of 51 |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | 0 of 45 | 1 of 51 | 1 of 96 | 0 of 49 | 0 of 45 | 0 of 51 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 45 | 1 of 51 | 1 of 96 | 0 of 49 | 0 of 45 | 0 of 51 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Anifrolumab - Basic Regimen- Treatment Period | Anifrolumab - Intensified Regimen- Treatment Period | All Anifrolumab- Treatment Period | Placebo- Treatment Period | Anifrolumab - Basic Regimen- Follow up | Anifrolumab - Intensified Regimen- Follow up |
|---|---|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 6 of 45 | 9 of 51 | 15 of 96 | 9 of 49 | 0 of 45 | 0 of 51 |
| Upper respiratory tract infection | Infections and infestations | 8 of 45 | 7 of 51 | 15 of 96 | 8 of 49 | 0 of 45 | 0 of 51 |
| Urinary tract infection | Infections and infestations | 10 of 45 | 6 of 51 | 16 of 96 | 5 of 49 | 0 of 45 | 0 of 51 |
| Bronchitis | Infections and infestations | 4 of 45 | 7 of 51 | 11 of 96 | 6 of 49 | 0 of 45 | 0 of 51 |
| Herpes zoster | Infections and infestations | 6 of 45 | 4 of 51 | 10 of 96 | 4 of 49 | 0 of 45 | 0 of 51 |
| Diarrhoea | Gastrointestinal disorders | 3 of 45 | 4 of 51 | 7 of 96 | 10 of 49 | 0 of 45 | 0 of 51 |
| Cough | Respiratory, thoracic and mediastinal disorders | 4 of 45 | 3 of 51 | 7 of 96 | 4 of 49 | 0 of 45 | 0 of 51 |
| Pharyngitis | Infections and infestations | 3 of 45 | 4 of 51 | 7 of 96 | 2 of 49 | 0 of 45 | 0 of 51 |
| Oral herpes | Infections and infestations | 3 of 45 | 3 of 51 | 6 of 96 | 2 of 49 | 0 of 45 | 0 of 51 |
| Headache | Nervous system disorders | 2 of 45 | 3 of 51 | 5 of 96 | 4 of 49 | 0 of 45 | 0 of 51 |
Serious events with the highest arm-level rate: herpes zoster (6.7%), influenza (2.2%), abscess bacterial (2.2%), pyelonephritis acute (2.2%), lupus endocarditis (2.2%).
During the treatment period, serious adverse events affected 19 of 96 participants in the all-anifrolumab group and 8 of 49 in the placebo group. The basic-regimen group had 10 of 45 affected, and the intensified-regimen group had 9 of 51 affected. These are participant counts over the stated period, not estimates adjusted for follow-up time. The registry also reports other adverse events for 70 of 96 participants in the all-anifrolumab group and 33 of 49 in the placebo group during treatment.
Follow-up is reported separately. Serious adverse events affected 3 of 96 participants in the all-anifrolumab group and 3 of 49 in the placebo group; the basic-regimen group had 3 of 45 affected and the intensified-regimen group had 0 of 51 affected. The record reports 1 death in the all-anifrolumab follow-up group, 1 in the basic-regimen follow-up group, and 0 in the intensified-regimen and placebo follow-up groups. No deaths are reported for the treatment-period groups.
These figures should be read as counts within the registry’s defined groups and periods. They do not establish that a treatment caused an event, and the treatment and follow-up counts should not be combined into a single rate. The most frequent listed serious adverse event term was herpes zoster at 6.7%; influenza, abscess bacterial, acute pyelonephritis, lupus endocarditis, and systemic lupus erythematosus were each listed at 2.2%. Further details about event definitions, exposure time, attribution, and statistical comparison are not reported in the registry record.
13. What the Result Does, and Does Not, Mean
The posted primary results describe a Week 52-to-baseline UPCR ratio and a model-based comparison of combined anifrolumab with placebo. All four arm-level geometric mean ratios are below 1, which the registry defines as improvement from baseline. The sponsor’s comparison has a geometric mean ratio of 1.031, a 95% confidence interval from 0.621 to 1.713, and p = 0.905. The interval includes the no-difference reference for a ratio contrast and is broad, so the estimate does not precisely determine the comparative effect.
These results do not establish that the two groups are equivalent. Equivalence requires a prespecified 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. Nor do the results establish whether either individual anifrolumab regimen differs from placebo, because the reported sponsor comparison combines the regimens.
The outcome is a measure of urinary protein relative to creatinine, not a complete account of renal status or of every outcome important to participants. The registry lists complete renal response as a secondary outcome, but the available primary result does not answer that separate question. Results for other outcome measures are not described in this interpretation.
The reported finding is limited to the participants with available primary outcome data in the stated analysis population and to the mixed-model method. The registry does not provide enough detail to assess missing-data assumptions, model specification, or the influence of missing measurements. The study is identified as phase 2 and enrolled 147 participants overall; the registry does not report the original sample-size justification. Consequently, the estimate should be read with its uncertainty and scope in mind, not as a standalone judgment of clinical benefit, absence of benefit, or safety.
The adverse-event counts are also descriptive. Differences in counts do not by themselves establish causal effects, and counts from separate treatment and follow-up periods should not be treated as directly comparable rates without information about exposure and ascertainment. The registry record supports description of the reported observations, while leaving several design and analysis details unreported.
14. Why This Trial Matters Statistically
This trial illustrates why a within-group change and a randomized between-group comparison answer different questions. The arm-specific geometric mean ratios describe Week 52 UPCR relative to baseline within each group. The sponsor’s mixed-model result instead compares all anifrolumab with placebo. A reader who focuses only on the fact that the arm estimates are below 1 could mistake improvement from baseline for evidence that one randomized strategy produced a different result from the other.
It also illustrates the importance of reading an estimate together with its confidence interval. The reported comparison is 1.031, but its interval extends from 0.621 to 1.713. The point estimate alone gives an incomplete picture of the uncertainty. The interval’s inclusion of 1 means the data do not clearly distinguish the groups on this ratio scale in the reported analysis; it does not demonstrate equivalence.
The population definition is another important statistical detail. The full analysis set includes participants who received at least one dose and were analyzed according to randomized treatment, while the endpoint count refers to those with available measurements. That distinction makes clear why overall enrollment and outcome analysis counts are not interchangeable, and why missing-data handling matters for interpretation.
Finally, the registry contains a combined-regimen comparison but not separate inferential comparisons for each dose regimen. This limits what can be concluded about the individual regimens from the reported primary analysis. The case emphasizes a general principle: interpret the exact estimand, analysis population, and model-based contrast that were reported, and do not infer additional comparisons from descriptive arm summaries.
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 registry record does not include the detailed statistical analysis plan, so the mixed model cannot be reconstructed from the posted summary. The model specification, covariance structure, covariates, transformation details, and missing-data assumptions are not reported in the registry record. These omissions limit independent assessment of how the sponsor’s estimate was obtained and how sensitive it may be to modeling choices.
The outcome analysis population is described as participants who received at least one dose and were analyzed according to randomized treatment, with available measurements determining the number analyzed. The reasons for unavailable data, the amount of missingness, and sensitivity analyses are not reported. Without this information, the effect of missing outcome data on the result cannot be evaluated from the registry summary.
The posted primary comparison combines the basic and intensified regimens. Separate sponsor comparisons against placebo are not reported in the registry record, which prevents a direct inferential reading of each regimen from the primary analysis. The record lists a secondary complete renal response outcome, but its result is not included in the primary figures. The multiplicity approach, if any, is also not reported.
The enrollment was 147, while the primary outcome arm counts reflect participants with available data. The registry does not report the original sample-size justification or enough information to judge the planned precision for the primary contrast. Planning illustrations based on observed effects are not a replacement for the original design rationale and are not observed power.
For safety, the registry gives participant counts by treatment and follow-up periods but does not provide exposure-adjusted rates, detailed attribution, or information sufficient to compare event risks formally. These limitations are specific to what is reported for this trial; they do not establish that additional analyses or documents do not exist outside the registry record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Safety and Efficacy of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Proliferative Lupus Nephritis — NCT02547922.
- Registry record last updated 2021-11-24; status last verified 2021-10.
- Results first posted 2021-11-24.
- 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.
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19. Record Summary
NCT02547922 is a completed, randomized, parallel-group, phase 2 study of anifrolumab plus standard of care versus placebo plus standard of care in adults with active proliferative lupus nephritis. The registry lists quadruple masking and enrollment of 147. The primary endpoint was the geometric mean ratio of 24-hour UPCR at Week 52 over baseline, with values below 1 indicating improvement from baseline.
The sponsor’s mixed-model comparison combined all anifrolumab regimens and compared them with placebo. It reported a geometric mean ratio of 1.031, a 95% confidence interval from 0.621 to 1.713, and p = 0.905. The interval includes 1 and indicates uncertainty about the comparative effect. The registry also lists complete renal response as a secondary outcome and reports safety counts separately for treatment and follow-up periods.
Important details—including the original sample-size justification, detailed model specification, missing-data handling, and multiplicity procedures—are not reported in the registry record. The results are therefore best interpreted as the reported primary comparison and descriptive safety information, with their stated analysis population and limitations.