A Study of LY2127399 in Participants With Systemic Lupus Erythematosus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY2127399 in Participants With Systemic Lupus Erythematosus (NCT01205438), a randomized phase 3 study. The primary outcome is Percentage of Participants Achieving an SLE Responder Index Response at Week 52.

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, parallel-group, quadruple-masked, placebo-controlled study of subcutaneous LY2127399 in participants with systemic lupus erythematosus. The study objective was to evaluate efficacy, safety, and tolerability when either of two LY2127399 regimens was added to standard of care therapy. The registry record lists an enrollment of 1124 and a completed status. The study start is recorded as 2011-01 and primary completion as 2014-08.

The intervention groups were LY2127399 every 2 weeks and LY2127399 every 4 weeks, with a placebo group as comparator. The registry describes alternating active and placebo injections every 2 weeks in the every-4-weeks regimen for blinding. The primary comparison is presented separately for each LY2127399 schedule against placebo; the record does not describe a direct randomized comparison between the two active schedules as the primary question.

The primary result is a binary outcome: whether each participant met the SLE Responder Index response definition at Week 52. The registry’s endpoint population is described as randomized participants who received at least one dose of study drug, with non-responder imputation included. Participants who dropped out or had missing Week 52 data were classified as non-responders, as were those unable to comply with allowed concomitant medication requirements.

The registry record does not report the original sample-size justification, its planned effect size, or the detailed statistical analysis plan. It also does not list sponsor-reported analysis records in the posted results. These omissions matter when interpreting recalculated comparisons: they should not be treated as a substitute for the trial’s prespecified analysis.

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: Intention to treat (ITT), all randomized participants who received at least one dose of study drug.Non-responder imputation (NRI) included.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving an SLE Responder Index Response at Week 52, measured over 52 weeks.

The primary endpoint is the percentage of participants achieving an SLE Responder Index response at Week 52. A participant had to meet all listed components: at least a 5 point reduction from baseline in SELENA SLEDAI score, no worsening in Physician’s Global Assessment (PGA), and no new BILAG A organ-domain score or 2 new BILAG B organ-domain scores compared with baseline. The registry defines no worsening in PGA as an increase of < 0.30 points from baseline.

The index combines changes across measures of lupus disease activity rather than relying on a single score. SELENA SLEDAI draws on descriptors across organ systems; PGA captures a clinician’s overall assessment; and BILAG records activity by organ domain. Requiring the stated conditions together is intended to identify improvement on the disease activity measure without specified worsening on the other measures. This general description explains the endpoint’s construction, not its clinical validity in any particular patient.

The registry also specifies how missing or unsuitable observations were handled for this endpoint: dropout, missing Week 52 data, or inability to comply with allowed concomitant medication requirements resulted in classification as a non-responder. This makes the endpoint a binary responder outcome under the stated imputation rule, not a complete-case summary of only participants with observed Week 52 assessments.

7. Results Posted in the Registry

• LY2127399 Every 2 Weeks: 38.4% (143/372) versus 27.7% (104/376) on control; risk difference 10.8 percentage points (95% CI 4.1 to 17.5), risk ratio 1.39 (1.13–1.71); unadjusted two-proportion z-test p = 0.002.
• LY2127399 Every 4 Weeks: 34.8% (131/376) versus 27.7% (104/376) on control; risk difference 7.2 percentage points (95% CI 0.6 to 13.8), risk ratio 1.26 (1.02–1.56); unadjusted two-proportion z-test p = 0.034.

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 Participants Able to Decrease Dose of Prednisone or Equivalent With No Increase in Disease Activity at Week 52

• 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:
  • LY2127399 Every 2 Weeks: 21.2% (31/146) versus 11.5% (15/131) on control; risk difference 9.8 percentage points (95% CI 1.2 to 18.4), risk ratio 1.85 (1.05–3.28); unadjusted two-proportion z-test p = 0.029.
  • LY2127399 Every 4 Weeks: 14.7% (19/129) versus 11.5% (15/131) on control; risk difference 3.3 percentage points (95% CI -4.9 to 11.5), risk ratio 1.29 (0.68–2.42); unadjusted two-proportion z-test p = 0.433.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for LY2127399 Every 2 Weeks 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 LY2127399 Every 4 Weeks and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline to 52 Weeks in Anti-double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Level

• 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:
  • LY2127399 Every 2 Weeks: mean -27.70 versus -7.00 on control; difference -20.70 (95% CI -29.50 to -11.90), standardized effect d = -0.34; z-test p = <0.001.
  • LY2127399 Every 4 Weeks: mean -26.40 versus -7.00 on control; difference -19.40 (95% CI -28.09 to -10.71), standardized effect d = -0.32; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for LY2127399 Every 2 Weeks than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for LY2127399 Every 4 Weeks than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline to 52 Week Endpoint in Physician's Global Assessment (PGA)

• 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:
  • LY2127399 Every 2 Weeks: mean -21.20 versus -15.10 on control; difference -6.10 (95% CI -9.31 to -2.89), standardized effect d = -0.27; z-test p = <0.001.
  • LY2127399 Every 4 Weeks: mean -19.20 versus -15.10 on control; difference -4.10 (95% CI -7.43 to -0.77), standardized effect d = -0.18; z-test p = 0.016.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for LY2127399 Every 2 Weeks than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for LY2127399 Every 4 Weeks than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes broaden the clinical picture beyond the Week 52 responder definition. They include steroid-dose reduction without increased disease activity, anti-dsDNA level, SLEDAI2K, severe flare timing, PGA, LupusQOL domains, PGA worsening, and fatigue. These outcomes address laboratory findings, disease activity, treatment burden, clinical assessments, and patient-reported experience. They are related to the primary result, but they are not interchangeable with the composite responder endpoint.

Across the posted results, there is no single uniform pattern across all secondary measures. The recalculated comparisons vary in estimated direction, uncertainty, and nominal p-values. In particular, intervals for some comparisons exclude zero while others span it. The secondary results should be read as separate outcome-specific summaries rather than as a vote in which a majority of outcomes establishes a unified conclusion.

The relationship to the primary result is contextual: secondary outcomes may show whether changes in components or related domains align with the composite result, but the registry record does not establish that each is confirmatory or that they were tested under a prespecified hierarchy. The posted results do not provide sponsor-reported analyses for the secondary outcomes.

Unadjusted secondary results carry less weight because multiple outcomes and comparisons create more opportunities for apparently notable findings by chance. Without a reported multiplicity plan, the unadjusted p-values cannot be interpreted as maintaining a stated overall false-positive rate across the full set of tests. The registry record also does not report which secondary outcomes were designated as key, whether testing order was specified, or whether any results were adjusted. Accordingly, these results can inform interpretation and motivate further study, but should not be treated as independent confirmation of the primary finding.

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

• Percentage of Participants Able to Decrease Dose of Prednisone or Equivalent With No Increase in Disease Activity at Week 52
• Change From Baseline to 52 Weeks in Anti-double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Level
• Change From Baseline to 52 Week Endpoint in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI2K) Score
• Time to First Severe SLE Flare (SFI)
• Change From Baseline to 52 Week Endpoint in Physician's Global Assessment (PGA)
• Change From Baseline to 52 Week Endpoint Lupus Quality of Life (LupusQOL) Domain Scores
• Percentage of Participants With No Worsening in Physician Global Assessment (PGA) Score at 52 Weeks
• Change From Baseline to 52 Week Endpoint in Brief Fatigue Inventory (BFI) Scores

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each participant is classified as a responder or non-responder according to the Week 52 SLE Responder Index definition. For a binary outcome, a group percentage describes the proportion classified as having the event—in this case, response. A comparison of two group percentages can be expressed as a risk difference, which subtracts the comparator proportion from the intervention proportion. A positive risk difference means the event proportion is higher in the intervention group in that unadjusted comparison. The recalculated risk differences are 0.108 for every-2-weeks LY2127399 versus placebo and 0.072 for every-4-weeks LY2127399 versus placebo.

Those risk differences are recalculations from posted counts and denominators, not adjusted model estimates. The record gives no sponsor-reported analyses for the endpoint, so there is no posted sponsor analysis against which to compare these calculations. The discrepancy indicator is false; nevertheless, the recalculations should be described accurately as unadjusted and should not be presented as the trial’s definitive prespecified analysis.

A confidence interval expresses uncertainty around an estimated effect under the assumptions of the method used. It gives a range of values compatible with the observed data and that method; it is not a range containing a guaranteed proportion of future effects, nor does it assign a probability to a fixed effect. For the primary comparison with every-2-weeks LY2127399, the recalculated risk-difference interval is 0.041 to 0.175. For every-4-weeks LY2127399, it is 0.006 to 0.138. Both intervals are positive, but their widths also matter: an interval gives information about precision, not only direction.

The p-value describes how unusual data at least as incompatible with a null hypothesis would be under the statistical model and its assumptions. The recalculated unadjusted p-values are 0.002 and 0.034 for the two primary comparisons. A p-value is not the probability that the null hypothesis is true, and it does not measure the clinical importance of an effect. It also does not account for multiplicity unless the analysis method explicitly incorporates it. The registry record does not report whether or how multiplicity was controlled.

The endpoint uses non-responder imputation. Under the registry description, participants who dropped out, lacked Week 52 data, or did not meet allowed concomitant medication requirements were classified as non-responders. This approach avoids treating missing outcomes as if they were observed responses, but it also makes the result dependent on the stated classification rule. The registry record does not provide enough detail to assess alternative missing-data assumptions or sensitivity analyses.

For the continuous secondary outcomes, the posted summaries give group means and standard deviations, and the recalculated comparisons are mean differences. A mean difference is the intervention-group mean minus the comparator-group mean as used in these calculations. The confidence interval describes uncertainty in that difference under the unadjusted calculation. Standard deviation describes variation among observations; it is not the same as the standard error, which describes uncertainty in an estimated mean. The posted comparisons include means, standard deviations, and standard errors for some continuous outcomes, but there are no sponsor-reported analysis records.

General statistical context: a t-test-style comparison of means can be affected by unequal variances or distributional features, particularly when summaries do not convey the full data shape. For event counts, over-dispersion means that variation exceeds what a simple count model expects; methods that account for that extra variation can produce more realistic uncertainty. The primary endpoint is binary rather than a count outcome, so over-dispersion is not the central issue for its risk-difference calculation. The registry does not report enough detail to determine the exact model used in the original analyses.

All recalculated p-values and confidence intervals should therefore be interpreted as transparent, unadjusted summaries based on the posted group statistics. They are useful for understanding the observed contrasts and their approximate precision, while the absence of a reported statistical plan limits conclusions about prespecification, adjustment, and confirmatory status.

11. Confidence Intervals and Precision

The primary risk-difference confidence interval for LY2127399 every 2 weeks versus placebo extends from 0.041 to 0.175. For LY2127399 every 4 weeks versus placebo, it extends from 0.006 to 0.138. Both are above zero, but the interval for the every-4-weeks comparison comes closer to zero. The estimates and intervals describe the uncertainty in the unadjusted recalculations, not in a sponsor-reported adjusted analysis.

Precision is not the same as clinical importance. A narrow interval would indicate less statistical uncertainty under the method, while a wider interval would leave a broader range of compatible effects. Whether an effect is important depends on clinical context and prespecified interpretation criteria, which are not reported in the registry record. The confidence intervals also do not resolve the issue of multiple comparisons.

For the posted continuous secondary outcomes, the mean-difference intervals likewise describe statistical uncertainty under the recalculation. They should be read alongside the outcome scale and the observed variability, rather than as stand-alone judgments about importance. No confidence intervals are posted for the arm-level percentages themselves in the posted summaries; the comparison intervals are the relevant recalculated uncertainty estimates.

These intervals do not account for unreported features of the original analysis plan, including any adjustment or model-based choices. Nor can a confidence interval correct for missing-data assumptions, endpoint-definition limitations, or selection among many outcomes. The registry record does not report sponsor analyses or sensitivity analyses that would show how robust the estimates are to alternative choices.

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 figures are planning illustrations derived from the observed effect, not the original trial design calculations. For these binary and continuous outcomes, the figures are participants per arm, rather than total events. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial’s own original design assumptions are not reported in the registry record.

The 80% power column gives the illustrative participants per arm for a design that would have an 80% chance of detecting the chosen effect under the stated assumptions, if that effect and model were correct. The 90% power column uses a higher target chance of detecting that effect, so it generally requires more participants per arm. These are design calculations, not probabilities that the completed study’s result is correct or that a treatment effect exists.

The rows that plan for 100% of the observed effect use the effect estimated from this study. The rows planning for 75% or 50% of the observed effect use smaller target effects, and smaller effects need more participants for the same nominal power. For the primary outcome, planning for 100% of the observed effect gives 298 participants per arm for 80% power and 398 for 90% power for the every-2-weeks comparison; the corresponding every-4-weeks figures are 653 and 874. The plotted curve should be read as a visual representation of the same planning relationship, not as observed evidence about power.

This is not observed power. The calculations are illustrations conditional on assumptions and observed effect estimates; they do not measure the chance that the completed trial detected a true effect.

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 = 0.277; treatment proportion p₁ = 0.384; average p̄ = 0.331.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6652 = 1.3038.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6609 = 0.5562.
4. n = (1.3038 + 0.5562)² / (0.1078)² = 297.6, rounded up to 298 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 <- 0.276595744680851                          # control proportion
p1 <- 0.384408602150538                          # 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(1205438)
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 = 298 (80% power), 398 (90% power)
 75% of observed effect: n per arm = 519 (80% power), 694 (90% power)
 50% of observed effect: n per arm = 1,141 (80% power), 1,527 (90% power)
power.prop.test: 297.6 
Simulated power at n = 298 per arm: 0.807 (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. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and a broad set of secondary outcomes, with comparisons against placebo for both LY2127399 schedules. Testing multiple outcomes and treatment comparisons raises a multiplicity question: if each test is judged separately at a conventional threshold, the chance of at least one false-positive result across the family can increase. Statistical plans may address this through procedures such as adjusted significance thresholds, hierarchical testing, or other prespecified strategies.

The registry record does not report whether such a procedure was planned or applied. It does not describe an outcome hierarchy, an adjustment method, or a family of comparisons used for error control. The recalculated p-values are explicitly unadjusted. They therefore describe each comparison on its own and cannot establish that multiplicity was controlled. This limitation is particularly relevant for the secondary results, where several domains and measures were assessed.

The record describes the primary endpoint population as intention to treat, consisting of randomized participants who received at least one dose of study drug, and states that non-responder imputation was included. The record further specifies that dropout, missing Week 52 data, and inability to comply with allowed concomitant medication requirements led to non-responder classification. It does not report alternative missing-data analyses, sensitivity analyses, or details needed to assess how other assumptions might affect the estimate.

The registry record does not report sponsor-reported analysis records, the original statistical analysis plan, or the original sample-size justification. The protocol’s planned interim analyses and sample-size assumptions are not reported in the registry record. As a result, it is not possible to verify from the posted record whether the recalculated tests match prespecified models, populations, or decision rules. These gaps do not invalidate the descriptive arm results, but they limit confirmatory interpretation and reproducibility.

15. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: herpes zoster (3.0%), pneumonia (1.9%), systemic lupus erythematosus (1.6%), abortion spontaneous (1.6%), anaemia (1.5%).

The registry lists serious adverse events during treatment for the LY2127399 every-2-weeks group as 46 among 371 at risk, for the every-4-weeks group as 59 among 374 at risk, and for placebo as 70 among 376 at risk. Follow-up entries are reported separately: 8 among 72 at risk for every-2-weeks LY2127399, 12 among 78 for every-4-weeks LY2127399, and 14 among 66 for placebo. These are serious adverse event counts and their listed at-risk denominators; they should not be conflated with non-serious adverse events or combined across treatment and follow-up periods.

The registry also lists serious adverse event terms with percentages, including Herpes zoster at 3.0%, Pneumonia at 1.9%, Systemic lupus erythematosus at 1.6%, Abortion spontaneous at 1.6%, Anaemia at 1.5%, and Leukocytosis at 1.5%. The record does not identify an arm for each listed term in these summaries. Death counts are not reported in the registry record. These listings describe reported safety data; they do not establish whether an event was caused by study treatment or permit a complete comparative safety assessment.

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

The primary result describes the proportion of participants meeting a specific composite response definition at Week 52 under the registry’s non-responder imputation rule. The posted percentages are higher in each LY2127399 group than in the placebo group. The recalculated unadjusted risk differences and confidence intervals quantify those observed contrasts and their statistical uncertainty under the calculation used.

That finding does not by itself establish the clinical importance of the difference. The registry record does not provide a threshold for a clinically meaningful between-group effect or the sponsor’s prespecified inferential results. The endpoint combines changes in SELENA SLEDAI, PGA, and BILAG, so its interpretation depends on the definition and the treatment of missing observations as well as on the observed percentages.

The result also does not establish that an individual participant will respond, predict an individual outcome, or determine how treatment should be chosen. Group-level percentages describe outcomes in the trial population and cannot be applied directly to an individual without additional clinical context. No medical advice follows from these registry summaries.

Nor does the primary comparison alone answer every question about the study. The secondary outcomes cover other dimensions of disease activity and experience, while safety summaries require careful separation of serious events, reporting periods, and causal attribution. The registry does not provide enough detail to reconstruct the complete statistical plan, the handling of all missing data, or any multiplicity adjustment. These boundaries support a cautious reading: the posted data show higher observed responder percentages in the active groups, while the strength and scope of confirmatory conclusions remain limited by the information reported.

17. Why This Trial Matters Statistically

This trial illustrates how a registry result can be statistically informative while still requiring attention to design and reporting details. The primary outcome is a composite binary endpoint, and its interpretation depends on all components being satisfied, as well as on the rule that classifies missing Week 52 observations as non-responses. Those choices shape the estimand—the treatment contrast the analysis is intended to describe.

The two active schedules are compared separately with placebo. Their recalculated unadjusted risk differences have positive confidence intervals, but the registry record does not report the original analysis plan or multiplicity procedure. This distinction matters because nominal evidence from separate unadjusted tests is not equivalent to a prespecified confirmatory conclusion across several comparisons.

The record also demonstrates the difference between observed results and planning illustrations. Sample-size figures based on observed effects can help readers understand how assumptions about target effect and power affect planning, but they are not the original design rationale and are not observed power. Without original design assumptions, the planning exercise cannot establish whether the trial was designed around a particular clinically meaningful effect.

Finally, the posted safety figures and secondary endpoints emphasize that efficacy is only part of trial interpretation. A careful statistical reading keeps the endpoint definition, population, missing-data rule, uncertainty, multiplicity, and limitations of registry reporting in view, without turning descriptive differences into medical recommendations.

18. 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.

The registry record does not include sponsor-reported analysis records, the full statistical analysis plan, or the original sample-size justification. Therefore, the recalculated unadjusted estimates cannot confirm that the same population, model, covariate adjustment, or decision rules were used in the trial’s prespecified analysis. The record also does not report whether interim analyses were planned or conducted.

The primary endpoint uses a composite of disease-activity measures, and the response definition requires all stated criteria. A participant’s classification can therefore depend on more than the change in SELENA SLEDAI alone. The record’s non-responder imputation rule classifies dropout and missing Week 52 data as non-response, but does not report sensitivity analyses under alternative assumptions or enough detail to assess the impact of missingness.

Multiple primary comparisons and secondary outcomes raise questions about multiplicity. No adjustment strategy or outcome hierarchy is reported, and recalculated p-values are unadjusted. Secondary findings should consequently receive less inferential weight than a result supported by a reported prespecified testing plan.

The serious adverse event summaries list counts and at-risk denominators, but the record does not provide an arm-specific breakdown for the listed serious event terms in the summaries. Death counts are not reported in the registry record. The available safety data also do not by themselves establish causation or supply the full detail needed for a benefit-risk assessment.

Finally, registry summaries do not reproduce all participant-level information or analysis diagnostics. The posted results support transparent description of the reported group summaries, but they cannot answer every question about adherence, outcome assessment, robustness, or generalizability.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study of LY2127399 in Participants With Systemic Lupus Erythematosus — NCT01205438.
• Registry record last updated 2018-07-17; status last verified 2018-06.
• Results first posted 2018-06-19.
• 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.

22. Record Summary

NCT01205438 is a completed phase 3 randomized, quadruple-masked, parallel-group, placebo-controlled study of subcutaneous LY2127399 added to standard of care for active systemic lupus erythematosus. The registry lists enrollment of 1124, with study start recorded as 2011-01 and primary completion as 2014-08.

The primary endpoint was SLE Responder Index response at Week 52. Posted response percentages were 38.5% with LY2127399 every 2 weeks, 34.8% with every-4-weeks dosing, and 27.7% with placebo. The recalculated unadjusted comparisons against placebo have positive risk differences, but the registry record does not report sponsor analyses, the original analysis plan, or multiplicity handling. The results are best read as posted group summaries with their recalculated uncertainty, not as a complete account of the trial’s planned statistical conclusions.