Efficacy and Safety of Atacicept in Systemic Lupus Erythematosus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Atacicept in Systemic Lupus Erythematosus (NCT01972568), a randomized phase 2 study. The primary outcome is Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Screening Visit as Baseline.

2. Clinical Question

3. Trial Design

This was a Phase IIb, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of atacicept in systemic lupus erythematosus. The registry record lists three treatment groups: atacicept 75 mg, atacicept 150 mg, and placebo. The official title describes a 24-week study, and the primary outcome was assessed at Week 24. The record lists enrollment of 306.

The primary endpoint was a binary response: each subject was classified as meeting or not meeting the SRI response definition at Week 24. The primary analysis population was the mITT set, defined in the record as all randomized subjects who had received at least one dose of investigational medicinal product. Posted primary outcome denominators were 102 for atacicept 75 mg, 104 for atacicept 150 mg, and 100 for placebo. The record does not explain in detail how missing Week 24 measurements were handled.

The trial started in 2013-12, reached primary completion in 2016-04, and is listed as completed. EMD Serono is identified as the sponsor. The record does not report the original sample-size justification, the protocol’s detailed statistical analysis plan, or the intended handling of interim analyses. These design details are not reported in the registry record and should not be inferred from the posted outcome results or from planning illustrations based on observed effects.

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: mITT analysis set included all randomized subjects who had received at least 1 dose of IMP.

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: Modified intent-to-treat (mITT) analysis set included all randomized subjects who had received at least 1 dose of investigational medicinal product (IMP).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Screening Visit as Baseline, measured over Week 24.

The primary endpoint is the percentage of subjects with an SRI response at Week 24, using screening as baseline. SRI is a composite measure of reduced systemic lupus erythematosus disease activity. To qualify as a responder, a subject had to have a reduction of at least 4 points in the SLEDAI-2K disease-activity score, no significant worsening in Physician’s Global Assessment, and no new BILAG A organ-domain score and no more than one new BILAG B organ-domain score. The record defines significant worsening in Physician’s Global Assessment as less than a 10% increase, with less than a 0.3-point increase used for statistical analyses.

A composite endpoint combines several criteria into a single response classification. In general, this can reflect more than one aspect of disease activity, while requiring that improvement in one component is not accompanied by specified worsening in others. It also means the reported percentage does not show which component drove a participant’s classification. The endpoint is a proportion meeting the full response rule at a particular assessment, not a measure of the magnitude of change in every participant. The record does not report separate primary results for each component of the SRI definition.

7. Results Posted in the Registry

• Atacicept 75 mg: 57.8% (59/102) versus 44.0% (44/100) on control; risk difference 13.8 percentage points (95% CI 0.2 to 27.5), risk ratio 1.31 (1.00–1.73); unadjusted two-proportion z-test p = 0.049.
• Atacicept 150 mg: 53.8% (56/104) versus 44.0% (44/100) on control; risk difference 9.8 percentage points (95% CI -3.8 to 23.5), risk ratio 1.22 (0.92–1.63); unadjusted two-proportion z-test p = 0.160.

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.

Percentage of Subjects at Week 24 Whose Prednisone-Equivalent Corticosteroid (CS) Dose Reduced From Screening by >=25% and to a Dose of =<7.5mg/Day, and no British Isles Lupus Assessment Group (BILAG) A or 2B Flare in Disease Activity

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Atacicept 75 mg: 17.9% (10/56) versus 18.9% (10/53) on control; risk difference -1.0 percentage points (95% CI -15.6 to 13.5), risk ratio 0.95 (0.43–2.09); unadjusted two-proportion z-test p = 0.892.
  • Atacicept 150 mg: 11.3% (6/53) versus 18.9% (10/53) on control; risk difference -7.5 percentage points (95% CI -21.1 to 6.0), risk ratio 0.60 (0.23–1.53); unadjusted two-proportion z-test p = 0.278.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Atacicept 75 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 Atacicept 150 mg and the control. The interval gives the range of effects that remain compatible with the data.

Change From Screening in Prednisolone-Equivalent Corticosteroid (CS) Daily Dose at Week 24

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Atacicept 75 mg: mean -2.64 versus -1.89 on control; difference -0.75 (95% CI -2.36 to 0.86), standardized effect d = -0.13; z-test p = 0.362.
  • Atacicept 150 mg: mean -1.87 versus -1.89 on control; difference 0.02 (95% CI -1.39 to 1.43), standardized effect d = 0.00; z-test p = 0.978.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Atacicept 75 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 Atacicept 150 mg and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Subjects With British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response at Week 24

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Atacicept 75 mg: 53.4% (47/88) versus 45.2% (42/93) on control; risk difference 8.2 percentage points (95% CI -6.3 to 22.8), risk ratio 1.18 (0.88–1.59); unadjusted two-proportion z-test p = 0.267.
  • Atacicept 150 mg: 49.0% (49/100) versus 45.2% (42/93) on control; risk difference 3.8 percentage points (95% CI -10.2 to 17.9), risk ratio 1.08 (0.80–1.46); unadjusted two-proportion z-test p = 0.593.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Atacicept 75 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 Atacicept 150 mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address several related dimensions: corticosteroid use, BICLA response, patient global impression, time to SRI response, adverse events, and SF-36 components. The posted results include corticosteroid dose reduction with disease-activity criteria, change in corticosteroid daily dose, and BICLA response. The overall pattern across these measures does not provide a uniformly separated picture across both atacicept groups and placebo. Some observed group percentages are higher in an atacicept group, while other measures are similar or show changes in different directions. The detailed numerical results are reported with their respective outcomes.

These secondary measures complement the primary SRI endpoint because they capture different definitions or aspects of response, including steroid use and BILAG-based assessment. Agreement across related outcomes could add context, while disagreement may reflect differences in endpoint definitions, available outcome denominators, or measurement properties. It should not be assumed that any one secondary measure validates or overturns the primary result. Several listed secondary outcomes do not have posted results; those results are not reported in the registry record.

Unadjusted secondary results carry less weight because many outcomes and comparisons can be examined. Without a reported multiplicity strategy, the chance of at least one apparently notable result among multiple tests is harder to assess. The registry record does not report a hierarchy, family-wise adjustment, or other correction for the secondary testing. Therefore, secondary findings are best read as descriptive and supportive rather than as independent confirmatory evidence. The primary result remains the principal endpoint for the trial’s stated efficacy question, while secondary outcomes help characterize the broader set of measures recorded.

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

• Percentage of Subjects at Week 24 Whose Prednisone-Equivalent Corticosteroid (CS) Dose Reduced From Screening by >=25% and to a Dose of =<7.5mg/Day, and no British Isles Lupus Assessment Group (BILAG) A or 2B Flare in Disease Activity
• Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24
• Change From Screening in Prednisolone-Equivalent Corticosteroid (CS) Daily Dose at Week 24
• Time From Randomization to First SRI Response During Treatment Period
• Percentage of Subjects With British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response at Week 24
• Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
• Change From Week 0 (Day 1) in SF-36 Components at Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

What does a binary endpoint comparison describe?

The primary endpoint classifies each participant as either meeting or not meeting the response definition. A group percentage is the proportion recorded as responders within that outcome group. Comparing these percentages can be expressed in different ways. A risk difference subtracts one group’s response proportion from the other; a risk ratio compares the proportions as a ratio; and an odds ratio compares the odds of response. These are distinct measures, so their numerical values are not interchangeable. General statistical interpretation: the risk difference is on the scale of absolute separation in proportions, whereas ratios express relative comparisons.

The registry’s recalculation uses posted group counts and denominators to form unadjusted comparisons. Unadjusted means the calculation does not account for covariates or other model terms. The sponsor’s reported analysis for atacicept 150 mg versus placebo used logistic regression and reported an odds ratio. Logistic regression models the odds of a binary outcome and can incorporate model terms, but the registry record does not specify all details of the sponsor’s model. In particular, any further adjustment variables or model diagnostics are not reported in the registry record.

Why can recalculated and sponsor analyses differ?

A recalculation from summary counts is a useful check on the direction and rough scale of a comparison, but it need not reproduce a sponsor’s model-based estimate or test. The methods may use different estimands, model terms, handling of incomplete observations, or analysis populations. The record does not specify which of these accounts for the discrepancy. It would be inappropriate to assign a cause without that information. Where a sponsor result is reported, that analysis takes precedence over the unadjusted recalculation.

The reported sponsor odds ratio of 1.56 compares the odds of response between atacicept 150 mg and placebo under the reported logistic-regression analysis. Its 95% confidence interval runs from 0.89 to 2.72. General statistical interpretation: an odds ratio of one corresponds to equal odds, and an interval including one is compatible with no group difference under the model and its assumptions. This does not prove the groups are identical; it indicates that the result does not precisely distinguish a difference from no difference.

What does a p-value contribute?

A p-value describes how compatible the observed data are with a specified null hypothesis, under the analysis assumptions. It is not the probability that the null hypothesis is true, nor is it a direct measure of the size or clinical importance of an effect. The unadjusted recalculation for the 75 mg comparison reports p = 0.049; for the 150 mg comparison it reports p = 0.16. These calculations do not supersede the sponsor’s reported analysis. The registry record does not report a thresholding or multiplicity strategy for interpreting these comparisons.

A result near a conventional threshold can be especially sensitive to analysis choices and rounding. It should be interpreted alongside the estimated effect, its uncertainty, the analysis population, and whether the comparison was part of a prespecified testing strategy. The sponsor’s full testing strategy is not reported in the registry record, so the recalculated p-value should not be treated as a definitive confirmatory finding.

Why do confidence intervals matter?

A confidence interval gives a range of effect estimates compatible with the observed data under the specified method. General statistical interpretation: wider intervals indicate less precision, while narrower intervals indicate greater precision. An interval crossing the null value for the measure does not establish equality. For an odds ratio, the null value is one; for a difference, it is zero. The primary sponsor-reported interval for the 150 mg comparison includes one, and the recalculated 150 mg difference interval spans values on both sides of zero. Those features indicate uncertainty about the direction and size of the treatment contrast.

Why can binary outcomes be sensitive to analysis choices?

In a binary outcome, each participant contributes a response classification, rather than a continuous measurement. The number of responders and the denominator both influence the estimate. Missing outcome status can matter if participants without an assessment are excluded, counted as nonresponders, or handled by another method. The registry record does not report the detailed missing-data method for the primary analysis. Consequently, the posted results should be read in the context of the stated mITT population, without assuming a particular imputation or missingness rule.

General statistical explanation: estimates from finite samples have sampling variability. A confidence interval makes some of that uncertainty visible; a point estimate alone does not. For binary outcomes, sparse response counts or small denominators can also make estimates unstable. The record gives group denominators and response percentages, but it does not provide enough information to reconstruct every element of the sponsor’s model or missing-data procedure.

What is the role of the secondary outcomes?

Secondary endpoints ask related questions, such as changes in corticosteroid dose or BICLA response. They can provide supporting context, but multiple endpoint and group comparisons create more opportunities for apparently notable findings to arise by chance. General statistical explanation: multiplicity procedures control the chance of false-positive conclusions across a family of tests, but the registry record does not report a multiplicity adjustment or testing hierarchy. Unadjusted secondary comparisons should therefore be treated as exploratory evidence rather than as independent confirmation of the primary result.

The registry lists a range of secondary outcomes, including patient-reported change, time to SRI response, adverse events, and SF-36 components. Results for several of these outcomes are not reported in the registry record. A missing posted result is not evidence of no effect or no event; it means that result cannot be interpreted from this record.

11. Confidence Intervals and Precision

The sponsor’s reported comparison of atacicept 150 mg with placebo has an odds ratio of 1.56 and a 95% confidence interval from 0.89 to 2.72. The interval is relatively broad on the odds-ratio scale and includes one, the value representing equal odds. This means the estimate is compatible with a range that includes no difference as well as differences favoring either group. It does not establish equivalence or rule out a potentially meaningful difference. The record does not report a threshold for clinical importance, so the interval cannot be judged against a registry-defined clinical margin.

The unadjusted recalculated risk-difference interval for atacicept 150 mg versus placebo extends from a negative value to a positive value. In general, that means the summary-data comparison is compatible with effects in either direction. The recalculated interval for atacicept 75 mg versus placebo is narrow enough to have a lower endpoint just above zero, but this unadjusted calculation does not replace the sponsor’s analysis. The record flags a discrepancy, and the sponsor’s own analysis takes precedence when available.

Confidence intervals communicate uncertainty in estimates under the method used; they do not show the full range of possible outcomes for individual participants. Nor do they account automatically for every source of uncertainty, such as model misspecification, missing data, or selective reporting. The primary results have denominators of 102, 104, and 100 across the three groups, and precision depends partly on the available outcome information. General statistical explanation: more information can improve precision, but the extent depends on the event frequency and analysis method. The registry record does not report a prespecified precision target for the primary comparison.

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 sample-size illustrations are planning calculations based on observed effects, not the original trial design. For these binary and continuous comparisons, the displayed figures are participants per arm, not total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each illustration uses the stated fraction of the observed effect as the effect to detect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column describes the number of participants per arm that the illustration estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if that effect were the true effect and the test assumptions held. The 90% power column expresses the corresponding planning target for a 90% chance. These are prospective design concepts: they are not measures of how likely the completed trial was to find a result after its data were observed.

Rows for 100% of the observed effect use the observed estimate as the planning target; rows for 75% and 50% use smaller effects. Smaller effects generally require more participants to distinguish them from random variation, which is why the figures increase as the target effect shrinks. Where the observed effect is very small, the resulting planning figures can become extremely large. Such calculations are sensitive to the observed estimate and are not a recommendation about a future trial’s design.

The illustrations are not observed power. Observed power calculated from the effect estimate after a trial is complete largely restates the result and does not resolve uncertainty. Confidence intervals and the original design rationale are more informative for interpreting the completed trial. The sample-size assumptions listed for these illustrations are known; the corresponding assumptions used to plan the trial itself are not reported in the registry record.

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 = 0.440; treatment proportion p₁ = 0.578; average p̄ = 0.509.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7070 = 1.3857.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.7002 = 0.5893.
4. n = (1.3857 + 0.5893)² / (0.1384)² = 203.5, rounded up to 204 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 <- 0.44                          # control proportion
p1 <- 0.57843137254902                          # 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(1972568)
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 = 204 (80% power), 272 (90% power)
 75% of observed effect: n per arm = 363 (80% power), 486 (90% power)
 50% of observed effect: n per arm = 816 (80% power), 1,092 (90% power)
power.prop.test: 203.5 
Simulated power at n = 204 per arm: 0.811 (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 reports one sponsor analysis for the primary endpoint: a logistic-regression comparison of atacicept 150 mg with placebo. The reported odds ratio is 1.56, with a 95% confidence interval from 0.89 to 2.72. This is the sponsor’s own analysis and takes precedence over the simple unadjusted recalculation from posted group summaries. Because the interval includes one, the reported analysis does not precisely distinguish a difference in odds from no difference.

The summary-data recalculation for the same dose comparison gives an unadjusted p-value of 0.16 and a difference interval that crosses zero. These calculations are not a substitute for the sponsor’s model. A recalculation is useful for checking how posted counts relate to an unadjusted comparison, but it may differ because the sponsor used a model-based method and may have applied analysis choices not fully described in the registry record.

For atacicept 75 mg versus placebo, the unadjusted recalculation gives p = 0.049. The registry does not report a sponsor analysis for that primary comparison. Since the record flags a discrepancy between recalculated and sponsor-reported analyses, the sponsor’s analysis takes precedence wherever it is available; the 75 mg recalculation should not be presented as though it were a sponsor-confirmed result. The registry record does not provide enough detail to explain the discrepancy or to infer the sponsor’s complete testing strategy.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary endpoint and several secondary outcomes, but it does not report a complete statistical analysis plan or a multiplicity procedure. It is therefore not possible to determine from this record whether the sponsor used a formal testing hierarchy, adjusted significance thresholds across doses, or controlled error across secondary outcomes. This matters because multiple comparisons increase the opportunity for chance findings. The unadjusted recalculations should not be interpreted as if they had been protected by a reported multiplicity strategy.

The primary analysis population is described as mITT: all randomized subjects who had received at least one dose of investigational medicinal product. The record provides primary outcome denominators for each group, but does not state how missing Week 24 assessments were handled, whether any imputation was used, or whether sensitivity analyses were conducted. Those details are not reported in the registry record. Without them, the consequences of missing outcome data cannot be fully assessed.

The record lists 10 outcome measures and three analyses, but does not provide all results or methods for every listed outcome. It also does not report details such as the original sample-size justification, interim analyses, model covariates, or a complete protocol-level analysis plan. Their absence does not show that these procedures were or were not used; they are simply not reported in the registry record. Interpretation should remain limited to the populations, outcome definitions, and analyses that are explicitly described.

16. 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 5% 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 (2.0%), acute kidney injury (2.0%), thrombocytopenia (1.0%), angina pectoris (1.0%), cardiac failure congestive (1.0%).

The registry reports serious adverse events for each group as counts of affected subjects and the corresponding group at risk: 9 of 102 for atacicept 75 mg, 6 of 104 for atacicept 150 mg, and 12 of 100 for placebo. These are descriptive counts over the trial’s reported safety period. They do not, on their own, establish that one group has a higher or lower underlying risk, and the record does not provide a comparative statistical analysis of serious adverse events.

The listed serious-event terms include systemic lupus erythematosus and acute kidney injury at 2.0% each, and thrombocytopenia, angina pectoris, cardiac failure congestive, and mitral valve prolapse at 1.0% each. The record does not give enough detail in these entries to attribute these terms to a particular treatment group. Death counts are not reported in the registry record.

Serious adverse events are not the same as all treatment-emergent adverse events. The registry also records other affected subjects, but those counts should be interpreted separately from the serious-event counts. Safety comparisons require attention to exposure, event definitions, follow-up, and uncertainty; detailed exposure-adjusted analyses are not reported in the registry record.

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

The primary outcome describes the proportion meeting a composite SRI response definition at Week 24 in each randomized treatment group. The posted percentages are higher for both atacicept doses than for placebo. The sponsor-reported logistic-regression analysis for atacicept 150 mg versus placebo has a confidence interval that includes no difference in odds, so it does not precisely establish a separation between those groups. The 75 mg unadjusted recalculation is not a substitute for a sponsor-reported analysis, and the record flags a discrepancy.

These findings do not establish that atacicept does or does not work. They describe the posted results for this trial, endpoint, analysis population, and time point. A response percentage does not show the experience of every participant, identify which component of the composite determined response, or establish the size of a clinically important effect. The registry record does not report a clinical-importance threshold for the primary endpoint.

The results also do not determine outcomes for people outside the trial population, under different treatment conditions, or beyond the recorded assessment period. The record does not report the original sample-size justification, complete missing-data methods, or full multiplicity plan, all of which constrain how confidently the posted comparisons can be interpreted. Secondary outcomes offer additional context but are not a replacement for the primary result, particularly when adjustment for multiple testing is not reported.

In general, a non-significant or imprecise result is not proof of equality, just as a nominally notable unadjusted result is not by itself proof of a reliable treatment effect. The most defensible reading combines the observed group outcomes with the sponsor’s analysis, its uncertainty, and the limitations of what the registry record reports.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison cannot be reduced to a single percentage or p-value. The primary outcome is a composite binary response, and the registry includes both observed group percentages and a sponsor-reported model-based comparison. The estimated effect, its confidence interval, the analysis method, and the analysis population all contribute to interpretation. The reported sponsor interval for the 150 mg comparison includes the null value, while the unadjusted recalculation for the 75 mg comparison is close to a conventional threshold. These results need different qualifications rather than a simple yes-or-no label.

The record also highlights the value of distinguishing a planned analysis from an independent recalculation. Summary counts allow readers to examine unadjusted comparisons, but they do not reproduce every feature of a model-based analysis. When the record flags a discrepancy, the sponsor’s own analysis takes precedence where reported, and unexplained differences should not be assigned a cause without methodological details.

Finally, the planning illustrations show how sample-size requirements depend on the effect a future study aims to detect. Smaller target effects require more participants under the stated assumptions. These calculations are not observed power and should not be mistaken for the trial’s original design rationale, which is not reported in the registry record. Together, these statistical distinctions help keep the interpretation tied to what the trial actually reports.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several limitations specific to this record affect interpretation. The sponsor’s own primary analysis is reported for atacicept 150 mg versus placebo, but not for atacicept 75 mg versus placebo. The record flags a discrepancy between sponsor and recalculated analyses, yet does not explain its source. The sponsor analysis should take precedence where available; the unadjusted 75 mg calculation cannot stand in for a missing sponsor result.

The record does not report the original sample-size calculation or the trial’s design assumptions. The planning illustrations are based on observed effects and specified assumptions, so they cannot establish whether the study was designed to detect a particular clinically important difference. The detailed missing-data procedure, any sensitivity analyses, full logistic-regression specification, and multiplicity strategy are also not reported in the registry record.

The primary endpoint is a composite response measure. The record does not provide separate primary results for its component criteria, limiting assessment of which elements contributed to the group percentages. Secondary results are posted for only some of the listed outcomes, and the available secondary comparisons are not reported with a multiplicity adjustment. The safety record provides serious-event counts and selected terms, but does not provide a comparative safety model or exposure-adjusted analysis. These omissions constrain conclusions; they should not be interpreted as evidence that a particular analysis was or was not conducted.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of Atacicept in Systemic Lupus Erythematosus — NCT01972568.
• Registry record last updated 2018-01-02; status last verified 2017-12.
• Results first posted 2017-10-26.
• 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

NCT01972568 is a completed Phase IIb, randomized, double-blind, placebo-controlled, parallel-group study of atacicept in systemic lupus erythematosus. The registry lists atacicept 75 mg, atacicept 150 mg, and placebo, with enrollment of 306. The study started in 2013-12 and reached primary completion in 2016-04.

The primary outcome was SRI response at Week 24 in the mITT population. Posted response percentages were 57.8% for atacicept 75 mg, 53.8% for atacicept 150 mg, and 44.0% for placebo. The sponsor reports a logistic-regression odds ratio of 1.56 for atacicept 150 mg versus placebo, with a 95% confidence interval from 0.89 to 2.72. The registry flags a discrepancy with recalculated analyses, and the sponsor’s own analysis takes precedence where reported.

Secondary outcomes and serious adverse-event counts provide additional descriptive context. The record does not report several details needed for a fuller assessment, including the original sample-size justification, complete missing-data methods, and multiplicity plan.