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Efficacy and Safety of Vedolizumab With Advancing Age in Patients With Crohnʼs Disease: Results From the GEMINI 2 Study

2015· article· en· W2977959782 on OpenAlexaff
Vijay Yajnik, Nabeel Khan, Marla C. Dubinsky, Jeffrey Axler, Alexandra Green, Brihad Abhyankar, Karen Lasch

Bibliographic record

VenueThe American Journal of Gastroenterology · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsVedolizumabMedicineInternal medicinePlaceboAdverse effectPopulationGastroenterologyPost-hoc analysisSurgeryInflammatory bowel diseaseDiseasePathology

Abstract

fetched live from OpenAlex

Introduction: Vedolizumab (VDZ) is a gut-selective monoclonal antibody to a4b7 integrin for the treatment of patients (pts) with Crohn's disease (CD). The efficacy and safety of VDZ have been demonstrated in the GEMINI 2 study.1 Here we report post hoc analyses of data from GEMINI 2 that evaluate the effects of VDZ with advancing age in pts with CD. Methods: In GEMINI 2, pts received double-blind (DB) VDZ or placebo (PBO) (induction intent-totreat [ITT] population) or open-label VDZ at weeks 0 and 2. At week 6, responders to VDZ induction treatment were re-randomized to receive DB VDZ every 8 weeks (Q8W) or 4 weeks (Q4W) or PBO up to week 52 (maintenance ITT population). Efficacy endpoints and adverse events (AEs) were analyzed by baseline (week 0) age category (55 years). Results: At baseline, 178 (48%), 161 (44%), and 29 (8%) pts in the induction and 246 (53%), 179 (39%), and 36 (8%) pts in the maintenance ITT populations were aged 55 years, respectively. At week 6, 31 (28%) VDZ-treated pts aged 55 years had an enhanced clinical response (≥100-point reduction in CD Activity Index [CDAI] score from baseline). Clinical remission (CDAI total score ≤150) was achieved by 16 (14%), 15 (16%), and 1 (8%) VDZ-treated pts in each age category, respectively. At week 52, remission was achieved by 65 (38%), 42 (37%), and 9 (41%) VDZ-treated pts aged 55 years, respectively. AEs occurred at similar rates across the ages (Table). Three malignancies ( < 1%) were reported in VDZtreated pts aged 20 years (carcinoid tumor of the appendix), 45 years (breast cancer), and 52 years (squamous cell carcinoma [skin]). Five deaths were reported: 3 VDZ-treated pts aged < 35 years (myocarditis; CD and sepsis; septic shock), 1 VDZ-treated pt aged 46 years (intentional overdose), and 1 PBO-treated pt aged 75 years (bronchopneumonia). Conclusion: These data suggest that the safety and efficacy of VDZ were generally similar in CD pts across all the age categories analyzed. Data interpretation is limited by the small pt population aged >55 years; these findings should be further evaluated in prospective studies.Table 1: Adverse Events Reported in Patients with CD by Baseline Age Category (GEMINI 2)

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)0.003
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.005
GPT teacher head0.220
Teacher spread0.215 · 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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Citations1
Published2015
Admission routes1
Has abstractyes

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