Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus (NCT02446912), a randomized phase 3 study. The primary outcome is Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index ≥4 (SRI[4]) at Week 52 (Original Analysis With Restricted Medication Rules).

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, parallel-group Phase 3 study with placebo control. The registry lists the trial as completed and records enrollment of 460. The study evaluated anifrolumab at 150 mg and 300 mg against placebo in adults with active systemic lupus erythematosus. Its brief summary characterizes the intended population as having moderately to severely active, autoantibody-positive SLE and describes an intravenous treatment regimen.

The primary outcome was the number of participants achieving SRI[4] at Week 52, using the original analysis with restricted medication rules. The primary analysis population is defined in the registry as the full analysis set: randomized participants who received at least one dose of investigational product. The outcome is a participant count, and the posted primary group results are 35 of 93 for anifrolumab 150 mg, 65 of 180 for anifrolumab 300 mg, and 74 of 184 for placebo.

The registry also lists 22 outcome measures, 15 analyses, and 15 posted secondary outcomes. These include response measures at Week 24 and Week 52, oral corticosteroid reduction, skin activity, flare rate, and adverse events. The registry record does not report the original sample-size justification, the detailed randomization procedure, or the trial’s original statistical analysis plan. The planned enrollment figure should therefore not be treated as an explanation of how the original design assumptions were chosen. Dates recorded for the study are a start date of 2015-06-09 and a primary completion date of 2018-07-17.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set - all randomized participants who received at least one dose of investigational product.

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: Full analysis set - all randomized participants who received at least one dose of investigational product.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index ≥4 (SRI[4]) at Week 52 (Original Analysis With Restricted Medication Rules), measured over Week 52.

The primary endpoint counts participants who met the SLE Responder Index criterion, SRI[4], at Week 52. The registry defines response as a reduction from baseline of at least 4 points in SLEDAI-2K, with no new organ systems affected under the specified BILAG-2004 criteria, and no worsening in lupus disease activity as measured by the Physician’s Global Assessment. It also requires no discontinuation of investigational product and no restricted medication use beyond the prespecified analysis threshold.

A composite response endpoint combines several criteria. This can make the result more informative than a change in one disease-activity measure alone: a participant must meet all the listed conditions to count as a responder. At the same time, the endpoint’s meaning depends on its exact definition and analysis rules. Here, restricted medication rules are part of the primary outcome definition, so the result is not simply a count of participants whose disease score improved.

The endpoint is reported as a count of participants rather than a continuous measure. The posted group counts are 35 of 93 for anifrolumab 150 mg, 65 of 180 for anifrolumab 300 mg, and 74 of 184 for placebo. These counts describe the recorded responder results in the analysis population; they do not by themselves establish how precisely the treatment groups differ. The comparison estimates and their confidence intervals are needed to assess the uncertainty around differences between groups.

7. Results Posted in the Registry

• Anifrolumab 150 mg: 37.6% (35/93) versus 40.2% (74/184) on control; risk difference -2.6 percentage points (95% CI -14.7 to 9.5), risk ratio 0.94 (0.68–1.28); unadjusted two-proportion z-test p = 0.678.
• Anifrolumab 300 mg: 36.1% (65/180) versus 40.2% (74/184) on control; risk difference -4.1 percentage points (95% CI -14.1 to 5.9), risk ratio 0.90 (0.69–1.17); unadjusted two-proportion z-test p = 0.420.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 at Week 52 in the Interferon (IFN) Test-High Sub-Group (Original Analysis With Restricted Medication Rules)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Anifrolumab 150 mg: 39.5% (30/76) versus 39.1% (59/151) on control; risk difference 0.4 percentage points (95% CI -13.1 to 13.9), risk ratio 1.01 (0.72–1.42); unadjusted two-proportion z-test p = 0.953.
  • Anifrolumab 300 mg: 35.8% (53/148) versus 39.1% (59/151) on control; risk difference -3.3 percentage points (95% CI -14.2 to 7.7), risk ratio 0.92 (0.68–1.23); unadjusted two-proportion z-test p = 0.560.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Anifrolumab 150 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Anifrolumab 300 mg and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants Who Achieved and Maintained an Oral Corticosteroid (OCS) Dose of ≤7.5 mg/Day in the Sub-group of Participants With Baseline OCS ≥10 mg/Day (Original Analysis With Restricted Medication Rules)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Anifrolumab 150 mg: 35.4% (17/48) versus 32.4% (33/102) on control; risk difference 3.1 percentage points (95% CI -13.2 to 19.4), risk ratio 1.09 (0.68–1.76); unadjusted two-proportion z-test p = 0.710.
  • Anifrolumab 300 mg: 40.8% (42/103) versus 32.4% (33/102) on control; risk difference 8.4 percentage points (95% CI -4.7 to 21.6), risk ratio 1.26 (0.88–1.81); unadjusted two-proportion z-test p = 0.211.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Anifrolumab 150 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Anifrolumab 300 mg and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With a ≥50% Reduction in CLASI Activity Score at Week 12 in the Sub-group of Participants With Baseline CLASI Activity Score ≥10 (Original Analysis With Restricted Medication Rules)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Anifrolumab 150 mg: 50.0% (15/30) versus 25.9% (14/54) on control; risk difference 24.1 percentage points (95% CI 2.7 to 45.4), risk ratio 1.93 (1.08–3.43); unadjusted two-proportion z-test p = 0.026.
  • Anifrolumab 300 mg: 41.4% (24/58) versus 25.9% (14/54) on control; risk difference 15.5 percentage points (95% CI -1.8 to 32.7), risk ratio 1.60 (0.93–2.75); unadjusted two-proportion z-test p = 0.084.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Anifrolumab 150 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Anifrolumab 300 mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover several related but nonidentical questions: response in an interferon test-high subgroup, oral corticosteroid dose reduction among participants with higher baseline doses, skin response among participants with a specified baseline CLASI score, response at Week 24, flare rate, BICLA response, and adverse events. The registry lists 22 outcome measures and 15 analyses, with 15 secondary outcomes posted. This range means the secondary evidence is not a single additional test of the primary question.

Across the posted secondary results with detailed recalculations, estimates differ in direction and precision. Some intervals include zero and others do not. The outcomes also vary in their analysis populations and timeframes. These differences make it inappropriate to combine them informally into a single conclusion or to regard a subgroup result as a substitute for the full analysis set primary result.

The Week 52 primary comparisons have unadjusted risk-difference intervals that include zero. Secondary findings can contribute information about other outcomes, but they do not erase the uncertainty in the primary endpoint. Conversely, a secondary result that appears more suggestive does not establish that the primary comparison has the same effect or that the result applies to all participants.

As a general statistical concern, multiple comparisons create more opportunities for apparently notable results to occur by chance. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting the secondary outcomes. Consequently, unadjusted secondary p-values carry less evidential weight than results interpreted under a known and appropriate multiplicity plan. The registry does not provide enough information to determine whether the posted secondary tests were confirmatory or exploratory, so their role should be described cautiously.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 at Week 52 in the Interferon (IFN) Test-High Sub-Group (Original Analysis With Restricted Medication Rules)
• Number of Participants Who Achieved and Maintained an Oral Corticosteroid (OCS) Dose of ≤7.5 mg/Day in the Sub-group of Participants With Baseline OCS ≥10 mg/Day (Original Analysis With Restricted Medication Rules)
• Number of Participants With a ≥50% Reduction in CLASI Activity Score at Week 12 in the Sub-group of Participants With Baseline CLASI Activity Score ≥10 (Original Analysis With Restricted Medication Rules)
• Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 (SRI[4]) at Week 24 (Original Analysis With Restricted Medication Rules)
• Annualized Flare Rate
• Number of Participants Who Met the Criteria for British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response (Original Analysis With Restricted Medication Rules)
• Number of Participants Reporting One or More Adverse Events (AE)
• Number of Participants Reporting One or More Adverse Events of Special Interest (AESI)

9. Statistical Interpretation

10. Statistical Methods Explained

What does a risk difference describe?

As a general statistical explanation, a risk difference compares the proportion of participants with an outcome in one group with the proportion in another group. A value near zero indicates similar observed proportions, while a negative or positive value indicates which group had the lower or higher observed proportion according to the order used for the comparison. The recalculated primary results compare each anifrolumab dose with placebo. The risk differences are -0.026 for 150 mg and -0.041 for 300 mg. These estimates are unadjusted calculations from posted summary counts.

A risk difference is an absolute-scale contrast. It is not the same quantity as a risk ratio or odds ratio, which compare groups using relative scales. The registry record also includes relative-scale recalculations, but the central interpretation uses risk differences and their confidence intervals. No adjusted risk-difference estimate is reported in these calculations.

What does the confidence interval add?

As a general statistical explanation, a confidence interval describes the range of estimates that are reasonably compatible with the data and the method used to calculate the interval. It communicates uncertainty around a point estimate; it does not assign a probability that the true effect lies in the particular interval. For the primary risk differences, both intervals extend across zero. That means the posted data and calculation do not distinguish a difference from no difference at the conventional confidence level represented by the interval. The span of each interval also shows that effects in either direction remain compatible with the estimates.

How should the p-values be read?

As a general explanation, a p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the analysis assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The recalculated unadjusted primary p-values are 0.678 for 150 mg and 0.42 for 300 mg. They should be read alongside the estimates and intervals, not in isolation. The registry’s sponsor-reported p-value for the 300 mg analysis is 0.412; the 150 mg sponsor analysis has no p-value reported in the registry record.

Why do the sponsor and recalculated results have different labels?

The participant counts support an unadjusted binary-outcome comparison expressed as a risk difference. In contrast, the sponsor-reported entries are labelled as mean differences in final values and list a Cochran-Mantel-Haenszel method for the 300 mg comparison. Because these labels describe different reported parameters, they should be presented as separate results rather than interpreted as duplicate estimates of the same measure. The registry record does not give enough detail to reconstruct the sponsor model or explain how its reported parameter relates to the count endpoint.

What do secondary outcomes contribute?

Secondary endpoints can examine other aspects of response, different time points, or subgroups. For example, the posted outcomes include response in an IFN test-high subgroup, oral corticosteroid reduction among participants with higher baseline OCS, and skin response among participants with a specified baseline CLASI activity score. These are distinct questions, and their populations and criteria differ from those of the primary endpoint. The available posted results should therefore not be treated as a collection of interchangeable replications of the primary result.

As a general statistical matter, examining multiple endpoints and comparisons increases the chance that some results will appear notable by chance if each is assessed separately without an appropriate multiplicity strategy. The registry record does not report the multiplicity procedure or a complete statistical analysis plan. The recalculated comparisons are unadjusted, so their p-values should not be treated as multiplicity-adjusted evidence.

11. Confidence Intervals and Precision

The two primary risk-difference intervals are broad enough to include zero and effects on either side of zero. For anifrolumab 150 mg versus placebo, the estimate is -0.026 and the 95% confidence interval runs from -0.147 to 0.096. For anifrolumab 300 mg versus placebo, the estimate is -0.041 and the interval runs from -0.141 to 0.059. Thus, neither estimate is precise enough to establish the direction of the difference from the unadjusted comparison alone.

A confidence interval is not a guarantee that the true effect lies within its limits. As a general explanation, it is an uncertainty summary based on the data and the method used to form it. The interval’s inclusion of zero indicates that no difference is among the values compatible with the calculation; it does not prove that the groups are identical. Similarly, the nonzero values within each interval indicate that differences of more than a negligible size remain possible on the risk-difference scale.

The registry also reports sponsor analyses with 95% confidence intervals for mean differences in final values. The 300 mg entry is -4.2, with an interval from -14.2 to 5.8; the 150 mg entry is -2.6, with an interval from -14.7 to 9.6. These are reported using a different parameter label from the unadjusted binary risk differences, so their numerical ranges should not be read as if they were the same scale.

Precision is affected by the amount of outcome information and by variability, among other considerations. As a general concept, more informative data can narrow an interval, while less informative data can leave a wider range of compatible effects. The registry does not report enough detail to attribute the observed interval widths to specific design or data features. The primary intervals are the most direct summary of uncertainty for the unadjusted group comparisons available from the posted counts.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations translate observed effects into hypothetical sample-size requirements under stated assumptions. Because the primary endpoint and other listed outcomes are binary counts, the displayed requirements are participants per arm, not total events. The registry’s sample-size assumptions specify two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. For each row, the effect to detect is the stated fraction of the observed effect. The original trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column describes the number of participants per arm estimated to give an 80% chance of detecting the chosen effect under those planning assumptions, if that effect and the assumptions were correct. The 90% power column uses a higher target chance of detection, and therefore generally requires more participants per arm for the same effect. These are planning quantities rather than observed outcomes. This is not observed power.

Rows that use 100% of the observed effect use the full observed difference as the hypothetical effect to detect. Rows that use 75% or 50% use smaller hypothetical effects. Smaller effects are harder to distinguish from random variation, so they require more participants per arm in these illustrations. The estimates based on very small observed differences can consequently imply very large planning requirements. Such values are especially sensitive to uncertainty in the observed effect and should not be read as proof that a future trial needs exactly that enrollment.

The figures are recalculated planning illustrations, not a reconstruction of the original trial’s design. They assume equal allocation between two arms, even though the registry’s trial includes two anifrolumab dose groups and placebo. The appropriate row is tied to a particular pairwise comparison and assumed effect size; it is not a universal enrollment recommendation. The sample-size display should be read as a sensitivity exercise showing how requirements change when the target effect changes, not as evidence that the completed trial was or was not adequately designed.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.402; treatment proportion p₁ = 0.376; average p̄ = 0.389.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6895 = 1.3515.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6893 = 0.5801.
4. n = (1.3515 + 0.5801)² / (-0.0258)² = 5,592.4, rounded up to 5,593 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.402173913043478                          # control proportion
p1 <- 0.376344086021505                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2446912)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 5,593 (80% power), 7,487 (90% power)
 75% of observed effect: n per arm = 9,973 (80% power), 13,350 (90% power)
 50% of observed effect: n per arm = 22,504 (80% power), 30,126 (90% power)
power.prop.test: 5592.4 
Simulated power at n = 5,593 per arm: 0.798 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry records sponsor-reported superiority analyses alongside the group counts. For anifrolumab 300 mg versus placebo, the reported method is Cochran-Mantel-Haenszel, and the result is a mean difference in final values of -4.2, with a 95% confidence interval from -14.2 to 5.8 and p = 0.412. For 150 mg versus placebo, the recorded mean difference in final values is -2.6, with a 95% confidence interval from -14.7 to 9.6; the p-value and method are not reported in that entry.

The recalculated comparisons use the posted responder counts and express the contrast as an unadjusted risk difference: -0.026 for 150 mg and -0.041 for 300 mg. The endpoints are both associated with the Week 52 primary outcome, but the registry’s reported sponsor parameter is labelled as a mean difference in final values, whereas the recalculation compares binary responder proportions. These estimates are not on the same reported scale and should not be treated as a direct numerical check of one another.

The registry record does not include enough analysis detail to recreate the sponsor’s method or clarify the relationship between the mean-difference label and the binary outcome counts. For interpretation of the trial, the sponsor’s own analysis takes precedence over a simple unadjusted recalculation. The recalculation is still useful as a transparent description of the group counts and an unadjusted contrast, but it does not supersede the sponsor’s analysis.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, treatment comparisons, time points, or subgroups are assessed. As a general statistical explanation, if each comparison is judged independently at a conventional threshold, the chance of at least one apparently notable result can rise as the number of tests grows. Procedures such as adjustment or a prespecified testing hierarchy can manage this issue, but the registry record does not report whether such a procedure was used for these results.

The registry lists 22 outcome measures, 15 analyses, and 15 posted secondary outcomes. The primary endpoint itself includes comparisons of each anifrolumab dose with placebo. The recalculated p-values are unadjusted, and the available information does not establish how multiplicity was handled in the sponsor’s own analysis. Secondary findings should therefore be interpreted with caution, particularly if they are considered individually without a stated analysis hierarchy.

The registry defines the primary full analysis set as randomized participants who received at least one dose of investigational product. That definition clarifies which participants were intended for the primary analysis, but the registry record does not report detailed missing-data handling for the primary endpoint. It also does not report imputation methods, assumptions about missing outcomes, sensitivity analyses for missing data, or a participant flow explanation that would permit fuller evaluation of missingness.

The registry record does not report the original statistical analysis plan, including details of endpoint models, covariate adjustment, interim analyses, or the sample-size justification. These items should not be inferred from the posted counts or from the recalculated planning illustrations. Without those details, the scope of confirmatory inference and the robustness of results to analytic choices cannot be fully assessed from the registry record alone.

16. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: systemic lupus erythematosus (2.7%), pneumonia (1.7%), asthma (1.1%), chest pain (1.1%), urinary tract infection (1.1%).

The registry reports serious adverse event counts by group. Serious events were reported for 10 of 93 participants receiving anifrolumab 150 mg, 27 of 180 receiving anifrolumab 300 mg, and 35 of 184 receiving placebo. These are participant counts in the respective groups, not event rates adjusted for exposure or duration. The registry also reports one or more other adverse events for 78 of 93, 157 of 180, and 141 of 184 participants, respectively.

Deaths are recorded as 0 in the 150 mg group, 1 in the 300 mg group, and 1 in the placebo group. The most frequently listed serious-event terms include systemic lupus erythematosus at 2.7%, pneumonia at 1.7%, asthma at 1.1%, chest pain at 1.1%, urinary tract infection at 1.1%, and atrial fibrillation at 1.1%. These term-specific percentages do not by themselves describe overall risk or establish that a treatment caused an event.

Safety counts are descriptive. They do not provide a complete account of event timing, duration, severity beyond the registry category, exposure-adjusted comparisons, or causal attribution. The registry record does not report enough detail to make those assessments from these figures alone.

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

The primary results describe the proportion of participants recorded as meeting the Week 52 SRI[4] definition in each treatment group and estimate the unadjusted differences from placebo. The observed counts are 35 of 93 for anifrolumab 150 mg, 65 of 180 for anifrolumab 300 mg, and 74 of 184 for placebo. The recalculated risk differences are negative for both dose comparisons, but both 95% confidence intervals include zero.

These findings do not establish that the groups are identical. The confidence intervals include a range of possible differences in both directions, so the results are compatible with no difference as well as with differences favoring either group. Nor should the estimates be turned into a claim about clinical benefit or lack of benefit: the posted counts and intervals describe the measured endpoint under the specified analysis rules, not every aspect of disease experience.

The endpoint is a composite responder definition with requirements about disease activity, new organ-system involvement, worsening, treatment discontinuation, and restricted medications. A participant’s status under this definition is not a complete description of all disease outcomes. Secondary measures can add context, but they concern distinct populations, criteria, or time points and are affected by the unreported multiplicity plan.

The sponsor-reported analyses use a mean-difference label and have their own confidence intervals. Those results should be distinguished from the unadjusted risk differences recalculated from the responder counts; they are not interchangeable measures. The safety counts likewise describe recorded events but do not alone establish causation or allow a complete risk comparison.

Overall, the registry supports a careful description of the observed groups and uncertainty around their comparisons. It does not support a definitive statement that one group is superior, that the groups are equivalent, or that the results apply beyond the studied population and outcome definitions. The absence of detailed information on missing data, multiplicity, and the original analysis plan further limits how far the registry results can be interpreted.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares two anifrolumab doses with placebo using a defined responder endpoint at Week 52. The randomized, double-blind, parallel-group design provides a framework for comparing assigned groups, while the posted group counts make the primary outcome readily interpretable as participants meeting or not meeting a composite criterion.

The results also illustrate why point estimates cannot be read alone. Both recalculated primary risk differences are negative, but their confidence intervals include zero and extend across effects in either direction. The estimates therefore communicate more than a simple responder-count ranking: they show substantial uncertainty around the observed differences. The sponsor’s reported analysis also underscores the importance of identifying the measure and method being reported, since its mean-difference label differs from the unadjusted binary risk difference.

Secondary outcomes make the interpretation more complex rather than simply more certain. They address several clinical domains, analysis populations, and time points. Without a reported multiplicity strategy, isolated secondary findings should not be taken as decisive confirmation or as a replacement for the primary result. Sample-size planning illustrations likewise require careful interpretation: they depend on assumed effects and stated calculation assumptions, and they are not evidence of observed power or of the original design rationale.

For biostatisticians and clinical researchers, the record highlights the value of examining endpoint definitions, analysis populations, effect scales, confidence intervals, and analysis transparency together. The posted information permits a descriptive and unadjusted assessment of the main count outcome, while key elements needed for a full evaluation of confirmatory inference are not reported in the registry record.

19. 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 analysis population is defined as randomized participants who received at least one dose of investigational product, but detailed missing-outcome counts and missing-data methods are not reported in the registry record. This limits assessment of how incomplete endpoint information may have affected the estimates or whether results are sensitive to assumptions about missing outcomes.

The sponsor-reported analysis entries are labelled as mean differences in final values, while the primary endpoint is described as a count of participants achieving a binary responder criterion. The registry record does not explain this parameter label or provide sufficient detail to reproduce those sponsor analyses. The unadjusted risk-difference recalculations are therefore a separate descriptive analysis and cannot substitute for the sponsor’s model-based results.

The registry record does not report the original statistical analysis plan, multiplicity procedure, interim-analysis plan, or sample-size justification. This is important because multiple outcomes and comparisons are listed, and the evidential status of secondary analyses depends in part on prespecification and multiplicity control. The planning illustrations use their own stated assumptions rather than the trial’s unreported original design assumptions.

The primary endpoint is a composite definition that includes disease activity, organ-system involvement, worsening, and medication-related rules. Its result is specific to that definition and the Week 52 assessment. Secondary outcomes address different criteria and subgroups, so they should not be interpreted as exact replications of the primary analysis. Finally, the safety figures are descriptive participant counts; detailed exposure-adjusted comparisons, timing, and causal attribution are not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus — NCT02446912.
• Registry record last updated 2023-01-12; status last verified 2022-12.
• Results first posted 2019-12-05.
• 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.

23. Record Summary

The registry record describes a completed, randomized, double-blind, parallel-group Phase 3 study of anifrolumab 150 mg, anifrolumab 300 mg, and placebo in adults with active systemic lupus erythematosus. Enrollment is recorded as 460. The primary outcome is SRI[4] response at Week 52 under restricted medication rules, analyzed in the full analysis set of randomized participants who received at least one dose.

The posted primary counts were 35 of 93 for 150 mg, 65 of 180 for 300 mg, and 74 of 184 for placebo. Unadjusted recalculated risk differences versus placebo were -0.026 and -0.041, respectively; both 95% confidence intervals include zero. Sponsor-reported results are recorded separately as mean differences in final values. The registry lists secondary response, steroid, skin, flare, and safety outcomes, but the original analysis plan, multiplicity procedure, missing-data methods, and sample-size justification are not reported in the registry record.