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S863 Real-World Clinical Effectiveness and Safety of Vedolizumab and Ustekinumab in Bio-naïve Patients With Late Crohn’s Disease: Results from the EVOLVE Expansion Study

2023· article· en· W4387750398 on OpenAlexaff
Britt Christensen, Michael Scharl, Brian Bressler, Yuliya Halchenko, Lauren Gianchetti, Pravin Kamble, Shashi Adsul, Zeinab Farhat, Marc Ferrante

Bibliographic record

VenueThe American Journal of Gastroenterology · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsThermo Fisher Scientific (Canada)St. Paul's Hospital
Fundersnot available
KeywordsMedicineVedolizumabUstekinumabDiscontinuationInternal medicineAdverse effectHazard ratioCrohn's diseaseSurgeryDiseaseAdalimumabConfidence interval

Abstract

fetched live from OpenAlex

Introduction: Real-world data comparing the clinical effectiveness and safety of vedolizumab (VDZ) and ustekinumab (UST) in patients (pts) with late Crohn’s Disease (CD, with a disease duration ≥2 years) is limited. Methods: EVOLVE Expansion (NCT05056441) was a multicenter, observational, retrospective medical chart review study in Australia, Belgium, and Switzerland from 2016 to 2021 in which biologic-naïve pts with CD (≥18 years old) initiated first-line biologic treatment with VDZ or UST were included. In this analysis, we assessed treatment outcomes in CD patients with late treatment commencement with biologics (disease duration >2 years). Data collected were from treatment initiation to chart abstraction, death, treatment discontinuation or loss to follow-up, whichever came first. The Kaplan Meier method was used to estimate cumulative rates of clinical response, remission, mucosal healing, and treatment persistence over 36 months. Serious adverse events (SAEs), serious infections (SIs), CD exacerbations and CD-related hospitalizations and surgeries were also evaluated. Baseline demographic and clinical characteristics across treatment groups were balanced using inverse probability weighting (IPW). Results: A total of 203 patients initiating late treatment with VDZ and 168 with UST were included. After IPW, both groups had similar baseline characteristics (Table 1). Over 36 months, cumulative rates were similar between VDZ- and UST-treated pts for clinical response (VDZ 82.1%, UST 86.7%; P=0.49), clinical remission (VDZ 89.9%, UST 91.6%; P=0.98) and mucosal healing (VDZ 90.5%, UST 88.2%, P=0.36). Treatment persistence was significantly higher with UST (VDZ 70.2%, UST 76.8%; P=0.03). There were no significant differences in the risk of safety outcomes: SAEs (hazard ratio [HR]=1.07; CI 0.56-2.04; P=0.83), SIs (HR=6.93; CI 0.71-67.28; P=0.10), CD exacerbations (HR=1.07; CI 0.70-1.61; P=0.76), CD-related surgeries (HR=0.87; CI 0.49-1.56; P=0.64) or CD-related hospitalizations (HR=1.48; CI 0.63-3.50; P=0. 37). Conclusion: In CD pts with late initiation of treatment with a biologic, there were no significant differences between the VDZ and UST cohorts for clinical response, clinical remission, or mucosal healing. The probability of treatment persistence was greater in pts treated with UST. The risks of CD-related surgeries, hospitalizations, and SIs were similar between cohorts. Table 1. - Baseline Charactersitics Unweighted Weighted Baseline Characteristics VDZN=203 USTN=168 P-value VDZN=185 USTN=186 Std Diff after IPW Age (years), mean ± SD 50.3±16.2 47.9±15.5 0.1593 49.5±15.9 50.2±15.9 0.0416 Male, n (%) 100 (49.3) 90 (53.6) 0.4084 94 (50.6) 93 (49.8) 0.0083 Disease duration (years), median (min, max) 10.3 (2.0, 52.6) 12.1 (2.1, 46.0) 0.3395 10.5 (2.0-52.6) 10.1 (2.1-46.0) 0.0206 CD location 0.0179 Colonic with/without upper GI disease, n (%) 53 (26.1) 26 (15.5) 37 (20.1) 40 (21.7) 0.0201 Ileal with/without upper GI disease, n (%) 87 (42.9) 75 (44.6) 68 (36.8) 75 (40.6) 0.0309 Ileocolonic with/without upper GI disease, n (%) 57 (28.1) 57 (33.9) 65 (35.4) 53 (28.5) 0.0029 Disease behavior 0.0625 Non-stricturing, non-penetrating, n (%) 124 (61.1) 86 (51.2) 116 (62.5) 92 (49.4) 0.0400 Penetrating, n (%) 9 (4.4) 18 (10.7) 15 (8.2) 20 (10.5) 0.0061 Stricturing, n (%) 61 (30.0) 58 (34.5) 33 (17.7) 47 (25.2) 0.0200 Disease severity 0.4837 Normal, n (%) 23 (11.3) 12 (7.1) 21 (11.1) 17 (9.1) Mild, n (%) 33 (16.3) 33 (19.6) 31 (16.9) 33 (17.6) 0.0053 Moderate, n (%) 108 (53.2) 96 (57.1) 98 (53.2) 110 (59.4) 0.0130 Severe, n (%) 16 (7.9) 9 (5.4) 14 (4.5) 12 (6.5) 0.0045 Active fistula* at index Yes, n (%) 24 (11.7) 29 (17.3) 0.1361 22 (11.8) 27 (14.3) 0.0023 Prior CD-related surgeries before treatment initiation Yes, n (%) 53 (25.7) 52 (31.0) 0.3025 54 (29.3) 57 (30.9) 0.0345 CD-related hospitalizations in previous 12 months Yes, n (%) 22 (10.8) 30 (17.9) 0.0525 25 (13.7) 25 (13.5) 0.0025 *Includes enterocutaneous, perianal, rectovaginal, other, and unknown. CD, Crohn’s disease; GI, gastrointestinal; IPW, inverse probability weighting; NA, not available; Std Diff, standardized difference; UST, ustekinumab, VDZ, vedolizumab.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

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)0.007
metaresearch head score (Gemma)0.008
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 score0.007
Threshold uncertainty score0.039

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0070.008
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.009
GPT teacher head0.272
Teacher spread0.264 · 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
Published2023
Admission routes1
Has abstractyes

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