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S983 Baseline Demographics and Disease Characteristics of Patients With Ulcerative Colitis Who Responded to Vedolizumab at Week 6

2022· article· en· W4316086137 on OpenAlexaff
Andrés Yarur, Vipul Jairath, Edward V. Loftus, Bruce E. Sands, Sharif Uddin, Qasim Khan

Bibliographic record

VenueThe American Journal of Gastroenterology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsWestern University
Fundersnot available
KeywordsMedicineVedolizumabUlcerative colitisInternal medicinePopulationClinical trialDemographicsGastroenterologySurgeryDiseaseDemography

Abstract

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Introduction: Vedolizumab (VDZ) has demonstrated efficacy for the treatment of patients with moderate to severe ulcerative colitis (UC). Identifying similarities in baseline characteristics among patients who respond to VDZ could be valuable to establish the patient population that is most suitable for treatment with VDZ. Methods: The baseline characteristics of patients with UC who responded to VDZ in the phase 3 clinical trials, GEMINI 1, VARSITY, and VISIBLE 1, and the phase 4 clinical trial, ENTERPRET, were pooled in order to identify similarities within the responder population. All four trials included adult patients with moderate to severe UC who had a prior inadequate response or loss of response to conventional therapies or anti-tumor necrosis factor alpha (anti-TNFα) treatment. Patients received VDZ 300 mg intravenously at weeks 0 and 2. The primary outcome was a response at week 6 defined as a decrease in partial Mayo score of ≥ 2 points and ≥ 25% from baseline, with a decrease in rectal bleeding sub-score of ≥ 1 or an absolute rectal bleeding sub-score of ≤ 1. Patient characteristics were analyzed using descriptive statistics, with mean or median values calculated across all four trials for continuous variables, and the number and proportion of responders reported for categorical variables. Results: Of the total of 1,183 patients enrolled across the four trials, 989 (83.6%) were White, while Black or African American patients were the most underrepresented group (2.8%). At week 6, 783 patients (66.2%) had a clinical response to VDZ. The baseline characteristics of these responders are shown in Table. Of the VDZ responders, the mean disease duration was 7.4 years, and 24.5% had experienced previous treatment failure with anti-TNFα treatment. Most responders had left-sided colitis or pancolitis (Table), and the majority had moderate or severe disease at baseline (complete Mayo score category: moderate, n = 333 [42.5%]; severe, n = 440 [56.2%]). For rectal bleeding and stool frequency sub-scores, rectal bleeding with obvious blood in stool and 5 or more stools than normal were the most frequently observed categories at baseline, respectively (Table). Conclusion: These baseline characteristics of patients who respond to VDZ at 6 weeks may serve as an indicator to determine which patients are most likely to respond to VDZ treatment. Table 1. - Baseline demographics and disease characteristics of patients who responded to VDZ treatment at week 6 Characteristic GEMINI 1 n = 122 ENTERPRET n = 131 VARSITY n = 263 VISIBLE 1 n = 267 Race, n (%) White 97 (79.5) 104 (79.4) 233 (88.6) 221 (82.8) Black or African American 3 (2.5) 12 (9.2) 0 2 (0.7) Asian 21 (17.2) 12 (9.2) 24 (9.1) 42 (15.7) Other 1 (0.8) 3 (2.3) 6 (2.3) 2 (0.7) Duration of disease, years, mean (SD) 6.5 (5.42) 8.3 (8.30) 7.3 (7.65) 7.6 (6.25) Disease location, n (%)a Proctosigmoiditis 8 (6.6) 22 (16.8) – 37 (13.9) Left-sided colitis 56 (45.9) 52 (39.7) – 112 (41.9) Extensive colitis 11 (9.0) 10 (7.6) – 20 (7.5) Pancolitis 47 (38.5) 47 (35.9) – 97 (36.3) Missing 0 0 – 1 (0.4) Complete Mayo score, median 8.0 8.0 9.0 9.0 Complete Mayo score, categories, n (%) Mild (score < 6) 4 (3.3) 3 (2.3) 2 (0.8) 0 Moderate (score 6–8) 62 (50.8) 68 (51.9) 105 (39.9) 98 (36.7) Severe (score 9–12) 56 (45.9) 60 (45.8) 155 (58.9) 169 (63.3) Missing 0 0 1 (0.4) 0 Mayo endoscopic sub-score, categories, n (%) Moderate disease 62 (50.8) 77 (58.8) 100 (38.0) 94 (35.2) Severe disease 60 (49.2) 54 (41.2) 162 (61.6) 173 (64.8) Missing 0 0 1 (0.4) 0 Partial Mayo score, median 6.0 6.0 6.0 6.0 Partial Mayo score, categories, n (%) Mild (score ≤ 4) 25 (20.5) 25 (19.1) 36 (13.7) 22 (8.2) Moderate (score 5–6) 49 (40.2) 56 (42.7) 114 (43.3) 115 (43.1) Severe (score 7–9) 48 (39.3) 50 (38.2) 113 (43.0) 130 (48.7) Rectal bleeding sub-score, categories, n (%) No blood seen 10 (8.2) 24 (18.3) 19 (7.2) 12 (4.5) Streak of blood with stool less than half of the time 40 (32.8) 35 (26.7) 70 (26.6) 78 (29.2) Obvious blood with stool most of the time 57 (46.7) 52 (39.7) 153 (58.2) 148 (55.4) Blood alone passes 15 (12.3) 20 (15.3) 21 (8.0) 29 (10.9) Stool frequency sub-score, categories, n (%) Normal number of stools 10 (8.2) 4 (3.1) 7 (2.7) 6 (2.2) 1–2 stools more than normal 21 (17.2) 22 (16.8) 32 (12.2) 33 (12.4) 3–4 stools more than normal 42 (34.4) 48 (36.6) 119 (45.2) 98 (36.7) ≥ 5 stools more than normal 49 (40.2) 57 (43.5) 105 (39.9) 130 (48.7) Anti-TNFα treatment status, n (%) Naive 80 (65.6) 5 (3.8) 217 (82.5) 156 (58.4) Failure 36 (29.5) 1 (0.8) 46 (17.5) 109 (40.8) Exposed, not failed 6 (4.9) 125 (95.4) 0 2 (0.8) SD, standard deviation; TNFα, tumor necrosis factor alpha; VDZ, vedolizumab. a, Disease location was not recorded for VARSITY.

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How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.029

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0090.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.004
GPT teacher head0.207
Teacher spread0.203 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2022
Admission routes1
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