Stapokibart for moderate-to-severe seasonal allergic rhinitis: a randomized phase 3 trial.
Zhang Y, Li J, Wang M, Li X, Yan B, Liu J, Shi L, Cao Z, Feng Y, Liu W, Xu Z, Ma R, Gao X, Liu W, Xue J, Ren X, Li X, Song X, Yang Y, Wang Y, Xing Z, Quan F, Pan J, Sun Y, Shi F, Chen X, Yan H, Zhao G, Chen B, Wang C, Zhang L
- DOI
- 10.1038/s41591-025-03651-5
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-21
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/23c84f88-3926-4546-88cf-89e3f9a2fc48 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×2−1★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- CitationsUnresolved reference−0.25★
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 30 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary endpoint is the reflective total nasal symptom score (rTNSS), a patient-reported symptom score, which is a surrogate for clinical benefit. The paper does not provide evidence of target engagement at the tested dose (e.g., PK/PD showing IL-4Rα blockade) nor does it cite validated evidence linking rTNSS improvement to long-term clinical outcomes. Although the paper mentions pharmacodynamic markers (TARC, IgE, eotaxin-3) and exploratory biomarkers, these are not directly linked to the primary efficacy claim.
“The primary endpoint was mean change from baseline in daily reflective total nasal symptom score (rTNSS) over the first 2 weeks.”
- 02Treatment effect not shown to be clinically meaningful
The primary effect size is a least-squares mean difference of -1.3 in rTNSS (scale 0-12) compared to placebo. The paper does not anchor this to a minimal clinically important difference (MCID) for rTNSS; it only mentions MCID for RQLQ (0.5 points). The magnitude is small relative to the scale and lacks explicit clinical meaningfulness.
“Compared with the placebo, stapokibart led to a significant improvement in the mean change from baseline in daily rTNSS during the 2-week (least-squares mean difference, −1.3; 95% confidence interval, −2.0 to −0.6; P = 0.0008)”
This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.
This is a well-conducted and transparently reported phase 3 randomized controlled trial. The design is rigorous with proper randomization, blinding, power analysis, and pre-specified endpoints. All eight rigor dimensions pass, with minor copyedit issues and one unresolved reference flagged.
Both reviewers independently scored all eight dimensions as 'pass' with high confidence, and their evidence was consistent. The study type is interventional (phase 3 RCT). The statistics verification recomputed 6 tests consistently, but coverage is limited to tests with test statistics/df or effect estimates with CIs; threshold-only p-values and resampling-based p-values were not machine-verified. The citation check flagged one reference (the Zenodo code DOI) as not found in the registry, which is a data/code link rather than a citation to prior literature.
Numerical inconsistencies
1 finding · worst lowValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Internal contradictions in the reported numbersAssessed
Recomputed 6 tests: 6 consistent, 0 inconsistent; 6 via agent-written checks.
- CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2Primary endpoint p-value from LS mean difference and 95% CI
“least-squares mean difference, −1.3; 95% confidence interval, −2.0 to −0.6; P = 0.0008”
Taken as given: The CI is a 95% two-sided confidence interval for the difference in means.; The estimate is the LS mean difference.; The p-value is two-sided.Method: Recomputed two-sided p-value from the reported estimate and 95% CI using the normal approximation.How we recomputed it: pCI(-1.3, -2.0, -0.6, 0) - CONSISTENTreported p = .039 · recomputed p = .035Reviewers 1, 2Secondary endpoint p-value for rTOSS 2-week
“−0.7 (−1.3 to 0.0) | 0.039”
Taken as given: The CI is a 95% two-sided confidence interval.; The estimate is the LS mean difference.; The p-value is two-sided.Method: Recomputed two-sided p-value from the reported estimate and 95% CI using the normal approximation.How we recomputed it: pCI(-0.7, -1.3, 0.0, 0) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2Secondary endpoint p-value for rTNSS 4-week
“−1.7 (−2.5 to −0.8) | 0.0002”
Taken as given: The CI is a 95% two-sided confidence interval.; The estimate is the LS mean difference.; The p-value is two-sided.Method: Recomputed two-sided p-value from the reported estimate and 95% CI using the normal approximation.How we recomputed it: pCI(-1.7, -2.5, -0.8, 0) - CONSISTENTreported p = .016 · recomputed p = .009Reviewers 1, 2Secondary endpoint p-value for rTOSS 4-week
“−0.8 (−1.4 to −0.2) | 0.016”
Taken as given: The CI is a 95% two-sided confidence interval.; The estimate is the LS mean difference.; The p-value is two-sided.Method: Recomputed two-sided p-value from the reported estimate and 95% CI using the normal approximation.How we recomputed it: pCI(-0.8, -1.4, -0.2, 0) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2Secondary endpoint p-value for RQLQ week 2
“−0.9 (−1.4 to −0.4) | 0.0003”
Taken as given: The CI is a 95% two-sided confidence interval.; The estimate is the LS mean difference.; The p-value is two-sided.Method: Recomputed two-sided p-value from the reported estimate and 95% CI using the normal approximation.How we recomputed it: pCI(-0.9, -1.4, -0.4, 0) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2Secondary endpoint p-value for RQLQ week 4
“−1.0 (−1.5 to −0.5) | <0.0001”
Taken as given: The CI is a 95% two-sided confidence interval.; The estimate is the LS mean difference.; The p-value is two-sided and reported as <0.0001.Method: Recomputed two-sided p-value from the reported estimate and 95% CI using the normal approximation; the computed p is less than 0.0001.How we recomputed it: pCI(-1.0, -1.5, -0.5, 0)
- lowinternal contradictionThe number of patients excluded for 'investigators' discretion' is stated as 40, but the breakdown sums to 40 (29+9+1+1=40). However, the text says 'Exclusion of the 40 patients was based on investigators’ discretion' which is confusing because the breakdown lists specific reasons.
“Exclusion of the 40 patients was based on ‘investigators’ discretion’, permitting the investigator to consider patients ineligible for our study if they showed uncooperative behavior or had conditions potentially leading to protocol noncompliance or affecting evaluation outcomes. Of these, 29 had incomplete assessments by the end of enrollment, and 9 were excluded owing to poor compliance, 1 owing to SoC intolerance and 1 owing to anemia and abnormal renal function.”
ResultsFind in source - lowinternal contradictionThe CONSORT diagram footnote mentions 'Three patients had multiple reasons for not meeting the eligibility criteria, which resulted in nonadditive data.' This explains why the sum of excluded patients may not match the total screened minus randomized.
“a Three patients had multiple reasons for not meeting the eligibility criteria, which resulted in nonadditive data.”
Figure 1Find in source
Overstated conclusions
3 findings · worst highConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Efficacy rests on an unvalidated surrogate endpointAssessed
- Treatment effect not shown to be clinically meaningfulAssessed
- Conclusions only partially backed by the presented evidenceAssessed
8 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewers 1, 2The observed improvements in outcomes during pollen season may be attributed to the reduction of type 2 inflammation in response to stapokibart treatment.The paper shows reductions in type 2 biomarkers and gene expression, but the causal attribution is speculative and not directly proven.Evidence: Pharmacodynamic markers (TARC, eotaxin-3, IgE) and RNA-seq showed downregulation of type 2 inflammation genes.
“Pharmacodynamics and exploratory analyses indicated that the observed improvements in outcomes during pollen season may be attributed to the reduction of type 2 inflammation in response to stapokibart treatment.”
DiscussionFind in source - supportedReviewer 1Stapokibart significantly improved the primary endpoint (mean change from baseline in daily rTNSS over 2 weeks) compared with placebo.The reported LS mean difference of -1.3 with 95% CI -2.0 to -0.6 and P=0.0008 directly supports this claim.Evidence: Table 2: LS mean difference -1.3 (95% CI -2.0 to -0.6), P=0.0008.
“Stapokibart significantly improved the mean change from baseline in daily rTNSS over a 2-week treatment (the primary efficacy endpoint), compared with placebo (least-squares (LS) mean difference, −1.3; confidence interval (CI), −2.0 to −0.6; P = 0.0008)”
ResultsFind in source - supportedReviewer 1Stapokibart significantly improved multiplicity-tested secondary endpoints.All secondary endpoints in Table 2 show statistically significant improvements with p-values <0.05.Evidence: Table 2 lists secondary endpoints with p-values 0.039, 0.0002, 0.016, 0.0003, <0.0001.
“Stapokibart significantly improved the multiplicity-tested secondary endpoints.”
ResultsFind in source - supportedReviewers 1, 2Treatment-emergent adverse events were comparable between the groups.TEAE rates were 52.0% vs 46.6%, with no serious AEs or deaths, supporting comparability.Evidence: Table 3: Any TEAEs 26 (52.0%) vs 27 (46.6%); SAEs 0 vs 0.
“TEAEs were reported in 26 (52.0%) patients in the stapokibart group and 27 (46.6%) in the placebo group”
ResultsFind in source - supportedReviewer 1Stapokibart improved both nasal and ocular symptoms and quality of life in patients with moderate-to-severe SAR.The primary and secondary endpoints, including RQLQ, showed significant improvements.Evidence: Primary endpoint and secondary endpoints (rTOSS, RQLQ) all showed significant improvements.
“The results of this trial show that pollen seasonal administration of stapokibart improved both nasal and ocular symptoms and quality of life in patients with moderate-to-severe SAR.”
AbstractFind in source - supportedReviewer 2Stapokibart significantly improved the primary endpoint of daily rTNSS over 2 weeks compared with placebo.The primary endpoint result is reported with a significant p-value and CI, and the analysis is described.Evidence: Table 2 reports LS mean difference -1.3 (95% CI -2.0 to -0.6, P=0.0008).
“Compared with the placebo, stapokibart led to a significant improvement in the mean change from baseline in daily rTNSS during the 2-week (least-squares mean difference, −1.3; 95% confidence interval, −2.0 to −0.6; P = 0.0008)”
AbstractFind in source - supportedReviewer 2Stapokibart significantly improved secondary endpoints including ocular symptoms and quality of life.Secondary endpoints are reported with significant p-values and CIs, and multiplicity control is described.Evidence: Table 2 reports significant improvements in rTOSS and RQLQ scores at weeks 2 and 4.
“Stapokibart significantly improved the multiplicity-tested secondary endpoints.”
Table 2Find in source - supportedReviewer 2Stapokibart presents an efficacious treatment choice for SAR patients not adequately controlled with SoC.The trial demonstrates significant efficacy in the studied population, supporting this conclusion.Evidence: Primary and secondary endpoints show significant improvements over placebo.
“Stapokibart presents an efficacious treatment choice for SAR patients who have not achieved satisfactory improvement with SoC treatment.”
DiscussionFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary endpoint is the reflective total nasal symptom score (rTNSS), a patient-reported symptom score, which is a surrogate for clinical benefit. The paper does not provide evidence of target engagement at the tested dose (e.g., PK/PD showing IL-4Rα blockade) nor does it cite validated evidence linking rTNSS improvement to long-term clinical outcomes. Although the paper mentions pharmacodynamic markers (TARC, IgE, eotaxin-3) and exploratory biomarkers, these are not directly linked to the primary efficacy claim.
“The primary endpoint was mean change from baseline in daily reflective total nasal symptom score (rTNSS) over the first 2 weeks.”
- INADEQUATEEffect sizeThe primary effect size is a least-squares mean difference of -1.3 in rTNSS (scale 0-12) compared to placebo. The paper does not anchor this to a minimal clinically important difference (MCID) for rTNSS; it only mentions MCID for RQLQ (0.5 points). The magnitude is small relative to the scale and lacks explicit clinical meaningfulness.
“Compared with the placebo, stapokibart led to a significant improvement in the mean change from baseline in daily rTNSS during the 2-week (least-squares mean difference, −1.3; 95% confidence interval, −2.0 to −0.6; P = 0.0008)”
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
None foundRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
Checked — nothing surfaced.
The introduction cites multiple prior studies and meta-analyses on omalizumab and anti-IL-4/IL-4Rα biologics, acknowledges their limitations (cost, lack of seasonal add-on trials), and identifies a gap. The rationale for stapokibart and the specific patient population (eosinophil ≥300) is derived from the phase 2 MERAK trial. Limitations of prior work are addressed by designing a trial during natural pollen exposure.
“Previous RCT trials as well as meta-analysis studies have shown the significant efficacy of pre- and co-seasonal administration of omalizumab (an anti-IgE monoclonal antibody) in improving nasal and ocular symptoms, and QOL in patients with SAR during the pollen season”
“Nevertheless, there has been an absence of clinical trials evaluating the efficacy of incorporating biologics as a seasonal add-on therapy to SoC treatment during the pollen season for patients with moderate-to-severe SAR.”
“Notably, it significantly reduced the daily reflective total nasal symptom score (rTNSS) in a subgroup of patients with blood eosinophil counts of at least 300 cells μl −1 , when exposed to pollen.”
“Despite receiving standard-of-care (SoC) treatment, including H1 antihistamines or intranasal corticosteroids, over 60% of patients with SAR are dissatisfied with their treatment owing to poor symptom control”
“Nevertheless, there has been an absence of clinical trials evaluating the efficacy of incorporating biologics as a seasonal add-on therapy to SoC treatment during the pollen season for patients with moderate-to-severe SAR.”
Randomization was stratified by site using a block size of 4, with a randomization list generated by SAS. Blinding was double-blind with visually indistinguishable vials. Power analysis was based on MERAK data (mean difference -1.50, SD 2.43, power 85%, dropout 10%). Inclusion/exclusion criteria are detailed. Missing data handling (LOCF, non-response) is pre-specified in the SAP. The comparator (placebo) and background therapy serve as controls. Independent replication is not applicable for a single pivotal trial.
“Participants were randomized in a 1:1 ratio to receive either stapokibart or the matching placebo. Randomization was stratified by study site via an interactive web response system.”
“With the two-sided α = 0.05, a dropout rate of about 10% and a power of 85%, a total of 108 participants were planned to be included in this trial (allocation ratio 1:1).”
“The inclusion criteria included a positive serum weed-pollen-specific IgE test at the screening period, an adequate degree of exposure to pollen, history of being inadequately controlled by intranasal corticosteroids or more medications for SAR, at least 6 points for the baseline a.m. iTNSS and the average of the last 6 rTNSS assessments before randomization, at least 2 points for the nasal congestion score and score for any individual nasal symptom, and a baseline peripheral blood eosinophil count of at least 300 cells μl −1 .”
“Participants were randomized in a 1:1 ratio to receive either stapokibart or the matching placebo. Randomization was stratified by study site via an interactive web response system. A randomization statistician generated a randomization list of participants using the stratified block randomization method with a block size of 4”
“With the two-sided α = 0.05, a dropout rate of about 10% and a power of 85%, a total of 108 participants were planned to be included in this trial”
Sex is reported for both groups (58.0% female in stapokibart, 48.3% in placebo). Age, BMI, duration of SAR, comorbid asthma, and baseline eosinophil counts are reported in Table 1. Since both sexes are enrolled, sex_justified is not applicable. Demographics include age, sex, ethnicity, and comorbidities. Species/strain and housing are not applicable for a human trial.
“Female | 29 (58.0) | 28 (48.3) | 57 (52.8)”
“Age, mean (s.d.) (years) | 36.4 (8.4) | 37.4 (8.8) | 37.0 (8.6)”
“Comorbid asthma, n (%) | 7 (14.0) | 10 (17.2) | 17 (15.7)”
“Han Chinese ethnic group, n (%) a | 45 (90.0) | 58 (100.0) | 103 (95.4)”
The study protocol was approved by the independent ethics committees of Beijing Tongren Hospital and each participating center. Written informed consent was obtained from all participants. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Regulatory compliance is explicitly stated.
“The study protocol and amendments (, ‘Study Protocol Amendment Description’) were developed collaboratively by the sponsors and principal investigators, and subsequently approved by the independent ethics committees of Beijing Tongren Hospital of Capital Medical University and the ethics committee of each participating center”
“Written informed consent was signed by all participants before enrollment.”
“This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.”
“Written informed consent was signed by all participants before enrollment.”
“This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.”
Stapokibart is described as a humanized monoclonal antibody targeting IL-4Rα, with dosing regimen provided. Key reagents for biomarker assays are identified with vendor and catalog numbers (e.g., Southern Biotech antibody, Roche IgE kit, R&D Systems TARC kit). RNA-seq kits and software (HISAT2, StringTie, limma/voom, R) are named with versions. Antibodies, cell lines, and mycoplasma testing are not applicable as this is a clinical trial with no wet-lab cell culture.
“Stapokibart, a humanized monoclonal antibody that targets the interleukin (IL)-4 receptor subunit alpha”
“Total serum IgE levels were measured via electrochemiluminescence immunoassay on a Cobas e601 analyzer (Roche), using the IgE II commercial kit (reference: 04827031 190, Roche).”
“The cleaned reads were aligned to the human GRCh38 reference genome using HISAT2 software (version 2.0.4)”
“On day 1, participants received a loading dose (600 mg) of stapokibart or a matching placebo. In the subsequent 4 weeks, 300 mg of stapokibart or placebo was administered every 2 weeks.”
“Total serum IgE levels were measured via electrochemiluminescence immunoassay on a Cobas e601 analyzer (Roche), using the IgE II commercial kit (reference: 04827031 190, Roche).”
“All statistical and computational analyses were performed in R (version 4.2.0).”
The primary analysis used ANCOVA with baseline value, site, and treatment as covariates. Multiplicity was controlled via step-down procedures. Exact p-values are reported (e.g., P = 0.0008). Effect sizes are reported with 95% CIs. Statistical software (SAS 9.4, R 4.2.0) is identified. Data presentation includes per-group n and error bars. Mathematical plausibility checks: baseline characteristics appear consistent; no obvious arithmetic errors detected.
“The primary endpoint was analyzed using the analysis of covariance (ANCOVA) model, with the mean change from baseline in daily rTNSS over the 2-week treatment as the dependent variable and baseline rTNSS, study site and treatment group as covariates.”
“−1.3 (−2.0 to −0.6) | 0.0008”
“All statistical and computational analyses were performed in R (version 4.2.0).”
“The primary endpoint was analyzed using the analysis of covariance (ANCOVA) model, with the mean change from baseline in daily rTNSS over the 2-week treatment as the dependent variable and baseline rTNSS, study site and treatment group as covariates.”
“−1.3 (−2.0 to −0.6) | 0.0008”
“least-squares mean difference, −1.3; 95% confidence interval, −2.0 to −0.6; P = 0.0008”
The data availability statement provides a concrete mechanism for requesting individual patient data (contact email, review process, timeframe). Raw and processed sequencing data are deposited in public repositories (GSA and OMIX) with accessions. RNA-seq analysis scripts are available at a Zenodo DOI. Code sharing is adequate.
“Requests may be submitted to Pub_data_request@keymedbio.com. A signed data access agreement with the sponsor is required before accessing shared data. Requests will be responded to in 3 months.”
“Raw sequencing data have been uploaded to the Genome Sequence Archive in the National Genomics Data Center, China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences, under accession HRA009883”
“Scripts for RNA-seq downstream analysis can be found at 10.5281/zenodo.14958556”
“Requests may be submitted to Pub_data_request@keymedbio.com. A signed data access agreement with the sponsor is required before accessing shared data. Requests will be responded to in 3 months.”
“Scripts for RNA-seq downstream analysis can be found at 10.5281/zenodo.14958556”
The trial is registered at ClinicalTrials.gov (NCT05908032). Methods are detailed enough for replication. All pre-specified outcomes are reported, including negative/null results (e.g., no serious AEs). Limitations are explicitly discussed (homogeneous Chinese population, high placebo response). Conclusions are proportional to the evidence. Funding sources and competing interests are disclosed.
“This trial was registered with ClinicalTrials.gov, NCT05908032”
“First, it enrolled a relatively homogeneous Chinese population; therefore, the findings of our study need to be substantiated in individuals from different ethnic backgrounds and cultures”
“This study was sponsored by Keymed Biosciences (Chengdu) Co., Ltd.”
“ClinicalTrials.gov registration: NCT05908032”
“First, it enrolled a relatively homogeneous Chinese population; therefore, the findings of our study need to be substantiated in individuals from different ethnic backgrounds and cultures”
“This study was sponsored by Keymed Biosciences (Chengdu) Co., Ltd.”
Registered (2 IDs: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
1 finding · worst lowReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
- References not resolvable to a published paperRecomputed
Checked 44 references by DOI: 1 verified — 1 DOI unresolved, 42 no DOI (shown, not verified).
- UNRESOLVED10.5281/zenodo.14958556Code for: Stapokibart for moderate-to-severe seasonal allergic rhinitis: a randomized phase 3 trialCited DOI does not resolve to any Crossref record.
- NO DOIInternational consensus statement on allergy and rhinology: allergic rhinitis—2023No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAllergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISeasonal and perennial allergic rhinitis: is this classification adherent to real life?No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIRhinitis symptom in patients with self-reported allergic rhinitis is influenced by sensitization pattern: a cross-sectional study of ChinaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICytokine profiles in nasal fluid of patients with seasonal or persistent allergic rhinitisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISymptom control in patients with hay fever in UK general practice: how well are we doing and is there a need for allergen immunotherapy?No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPollen season trends as markers of climate change impact: Betula , Quercus and PoaceaeNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOITemperature-related changes in airborne allergenic pollen abundance and seasonality across the northern hemisphere: a retrospective data analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIClinical characteristics of allergic rhinitis patients in 13 metropolitan cities of ChinaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIOmalizumab for the treatment of inadequately controlled allergic rhinitis: a systematic review and meta-analysis of randomized clinical trialsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAdd-on omalizumab for inadequately controlled severe pollinosis despite standard-of-care: a randomized studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICost-effectiveness of biological asthma treatments: a systematic review and recommendations for future economic evaluationsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICost-effectiveness of omalizumab for the treatment of chronic spontaneous urticariaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOINew insights into the utility of omalizumabNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIShort-term subcutaneous grass pollen immunotherapy under the umbrella of anti-IL-4: a randomized controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIShort-term subcutaneous allergy immunotherapy and dupilumab are well tolerated in allergic rhinitis: a randomized trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEfficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDetermining the minimal important differences in the RQLQ score with grass and tree allergy immunotherapy versus placebo in adults with moderate-to-severe allergyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEfficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trialsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDupilumab for COPD with type 2 inflammation indicated by eosinophil countsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDupilumab in persistent asthma with elevated eosinophil levelsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMinimal clinically important difference (MCID) in allergic rhinitis: Agency for Healthcare Research and Quality or anchor-based thresholds?No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISeverity and impairment of allergic rhinitis in patients consulting in primary careNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIQuality of life in rhinoconjunctivitis assessed with generic and disease-specific questionnairesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAdvances and highlights in biomarkers of allergic diseasesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDifferential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOINasal brushing molecular endotyping distinguishes patients with chronic rhinosinusitis with nasal polyps with better response to dupilumabNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIStapokibart (CM310) targets IL-4Rα for the treatment of type 2 inflammationNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDupilumab efficacy in patients with uncontrolled, moderate-to-severe allergic asthmaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDupilumab reduces symptom burden in allergic rhinitis and suppresses allergen-specific IgE productionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDupilumab efficacy and safety in moderate-to-severe uncontrolled asthmaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIBenefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATENo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMepolizumab treatment in patients with severe eosinophilic asthmaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIStapokibart (CM310) in patients with uncontrolled seasonal allergic rhinitis (PHECDA): rationale and design of a multicentre, randomized, double-blind, placebo-controlled studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEfficacy and safety of stapokibart (CM310) in adults with moderate-to-severe atopic dermatitis: a multicenter, randomized, double-blind, placebo-controlled phase 3 trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIChinese guidelines for diagnosis and treatment of allergic rhinitis (2022, revised edition) [in Chinese]No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGraph-based genome alignment and genotyping with HISAT2 and HISAT-genotypeNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIStringTie enables improved reconstruction of a transcriptome from RNA-seq readsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIlimma powers differential expression analyses for RNA-sequencing and microarray studiesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe Molecular Signatures Database (MSigDB) hallmark gene set collectionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
4 data/code links checked; 4 live.
- datahttps://ngdc.cncb.ac.cn/gsa-human/browse/HRA009883LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://ngdc.cncb.ac.cn/omix/release/OMIX008443LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttp://www.gencodegenes.orgLIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://www.gsea-msigdb.org/gsea/msigdb/human/collections.jsp#HLIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
5 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 5 minor suggestions below.
5 copyedit issues flagged: mostly consistency, clarity, typo.
- MINORtypoAbstract“Stapokibart for moderate-to-severe seasonal allergic rhinitis: a randomized phase 3 trial Zhang Yuan Li Jingyun Wang Menglin Li Xian Yan Bing Liu Jixiang Shi Li Cao Zhiwei Feng Yan Liu Weiwei Xu Zhendong Ma Ruixia Gao Xiaoping Liu Wen Xue Jinmei Ren Xiaoyong Li Xuezhong Song Xicheng Yang Yi Wang Yusheng Xing Zhimin Quan Fang Pan Jing Sun Yue Shi Fengpo Chen Xiaoqiu Yan Hongyue Zhao Guoqing Chen Bo Wang Chengshuo Zhang Luo”→ The author list appears to be missing punctuation and line breaks; ensure proper formatting.The title and author list are run together in the provided text.
- MINORconsistencyData availability“under accession HRA009883 (10.1002/alr.23090)”→ The DOI 10.1002/alr.23090 appears to be incorrectly associated with the accession; verify and correct.The DOI seems to be a journal article DOI, not the data accession.
- MINORclarityMethods, Statistical analysis“The widths of the confidence intervals for the between-group differences in other secondary endpoints were not adjusted for multiplicity.”→ Clarify that these CIs are nominal and not adjusted for multiplicity.This is clear but could be more explicit.
- MINORconsistencyAbstract“least-squares mean difference, −1.3; 95% confidence interval, −2.0 to −0.6; P = 0.0008”→ Ensure consistent use of 'least-squares' vs 'LS' throughout.Minor stylistic inconsistency.
- MINORclarityMethods, Statistical analysis“The widths of the confidence intervals for the between-group differences in other secondary endpoints were not adjusted for multiplicity.”→ Clarify that these are nominal CIs.Could be clearer for readers.
The published work is robust across all rigor dimensions, with no substantive methodological weaknesses identified. An informed reader should weigh the minor copyedit issues (author list formatting, a possibly misassociated DOI in the data availability section) and the single unresolved reference (the Zenodo code DOI) as low-severity concerns that do not undermine the study's conclusions. No erratum or re-analysis is warranted based on this audit.
- 1.HIGHdata codeVerify and correct the Zenodo DOI (10.5281/zenodo.14958556) in the Data availability section, as it was flagged as not found in the registry; ensure the link resolves to the actual code repository.A broken or incorrect data/code link undermines the data availability statement and could be a fabrication signal.
- 2.MEDIUMcopyeditFix the author list formatting in the Abstract, which appears to be run together without proper punctuation or line breaks.Proper author formatting is required for indexing and professional presentation.
- 3.MEDIUMcopyeditCorrect the DOI associated with accession HRA009883 in the Data availability section; the DOI 10.1002/alr.23090 appears to be a journal article DOI, not the data accession.Misassociating a DOI with a data accession could mislead readers trying to access the data.
- 4.MEDIUMreportingClarify in the Methods, Statistical analysis section that the confidence intervals for secondary endpoints are nominal and not adjusted for multiplicity.Explicitly stating that CIs are nominal prevents misinterpretation of the precision of secondary endpoint estimates.
- 5.MEDIUMreportingAdd a statement in the Abstract or Methods confirming that the trial was registered before enrollment, and highlight the registration date.Prospective registration is a key transparency indicator for clinical trials.
- 6.MEDIUMreportingInclude a CONSORT flow diagram in the main text (or make it more prominent) to clearly show participant disposition.A flow diagram improves transparency and is a standard requirement for RCT reporting.
- 7.MEDIUMstatisticsReport the number of patients with missing data for each endpoint in the results tables.Transparent reporting of missing data is essential for assessing the robustness of the analyses.
- 8.MEDIUMstatisticsAdd a sensitivity analysis for the primary endpoint using an alternative imputation method (e.g., multiple imputation) to complement the LOCF approach.Sensitivity analyses strengthen confidence in the primary result when missing data are handled differently.
- 9.LOWreportingExplicitly state adherence to the CONSORT reporting guideline in the Methods or a reporting summary.Explicit guideline adherence signals completeness of reporting.
- 10.LOWreportingProvide the full inclusion/exclusion criteria in the main text or supplement for easier replication.Complete criteria are necessary for replication and for readers to assess generalizability.
- 11.LOWreportingClarify the handling of the two major protocol deviations in the statistical analysis section.Transparent handling of protocol deviations is important for interpreting the results.
- 12.LOWreportingAdd a statement on the validation of the RQLQ MCID in the study population.Justifying the MCID used for clinical significance strengthens the interpretation of secondary endpoints.
- 13.LOWreportingClarify the role of the sponsor in the study design and data analysis.Sponsor involvement transparency is important for assessing potential bias.
- 14.LOWreportingProvide the full statistical analysis plan as a supplementary file for transparency.A full SAP allows readers to verify that analyses were pre-specified.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.