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P038 Comparing the Efficacy and Safety of Subcutaneous Vedolizumab Versus Adalimumab for the Treatment of Ulcerative Colitis: A Network Meta-Analysis

2019· article· en· W2993556900 on OpenAlexaff
Vipul Jairath, Keith Chan, Karen Lasch, Sam Keeping, Christian Agboton, Aimee Blake, Jeroen Jansen, Haridarshan Patel

Bibliographic record

VenueThe American Journal of Gastroenterology · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsPrecision Nanosystems (Canada)London Health Sciences CentreWestern University
Fundersnot available
KeywordsVedolizumabMedicineInternal medicineUlcerative colitisAdalimumabAdverse effectDiscontinuationRandomized controlled trialSurgeryDisease

Abstract

fetched live from OpenAlex

BACKGROUND: Vedolizumab (VDZ), a gut-selective monoclonal α4β7 integrin antibody, is approved for the treatment of moderately to severely active ulcerative colitis (UC) and Crohn’s disease. Intravenous (IV) VDZ was recently shown to be superior to subcutaneous (SC) adalimumab (ADA) in VARSITY (1), the first head-to-head randomized controlled trial (RCT) of biological therapies in UC. No comparative efficacy or safety data versus ADA exist for VDZ SC, a new formulation in development (2). To generate estimates of the comparative efficacy and safety of VDZ SC versus ADA, we conducted a network meta-analysis (NMA) of RCTs. METHODS: The NMA was conducted using results from a targeted literature review that identified RCTs of both VDZ and ADA: GEMINI 1, VISIBLE 1, ULTRA-2, and VARSITY. In the former two trials, responders were rerandomized at the end of induction, whilst the latter two trials were treat-through designs. To adequately analyze these trials in one network of evidence, efficacy outcomes were assessed conditionally upon response at start of maintenance. For treat-through studies, this was response at 6/8 weeks. Efficacy outcomes in the maintenance period were response and remission at 52/54 weeks. Safety outcomes were overall adverse events (AEs), serious AEs (SAEs), overall infections, serious infections, and AEs leading to discontinuation as reported at 52 weeks. Odds ratios (OR) with 95% credible intervals (CrI) were estimated using probit and binomial NMA models. ADA SC 40 mg Q2W, VDZ IV 300 mg Q4W, and VDZ IV 300 mg Q8W were all compared against VDZ SC 108 mg Q2W (reference group). RESULTS: ADA had lower rates for maintenance of response and remission relative to VDZ SC, but this was not statistically significant (ORs with 95% Crl: 0.60 [0.33, 1.08] and 0.59 [0.33, 1.09], respectively). Although overall AEs were significantly higher with ADA compared with VDZ SC (OR 2.02 [1.04, 3.89]), other safety outcomes were similar: overall infections, OR 1.86 (0.94, 3.77); serious AEs, OR 1.41 (0.54, 3.75); serious infections, OR 0.39 (0.05, 2.73); AEs leading to discontinuation, OR 2.58 (0.80, 9.44). As expected, VDZ IV had similar maintenance efficacy and safety outcomes relative to VDZ SC. CONCLUSION(S): Results from this indirect treatment comparison suggest that VDZ SC may achieve higher rates of maintenance response and remission among responders at start of maintenance than ADA and is associated with a lower risk of overall AEs. In the absence of a head-to-head trial between VDZ SC and ADA SC, these findings support a favorable benefit-risk profile of VDZ SC in UC.

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)0.025
metaresearch head score (Gemma)0.040
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.025
Threshold uncertainty score0.131

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0250.040
Meta-epidemiology (narrow)0.0040.002
Meta-epidemiology (broad)0.0140.053
Bibliometrics0.0040.005
Science and technology studies0.0010.001
Scholarly communication0.0030.002
Open science0.0030.002
Research integrity0.0030.003
Insufficient payload (model declined to judge)0.0070.001

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 head0.024
GPT teacher head0.275
Teacher spread0.251 · 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 designMeta-analysis
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
Published2019
Admission routes1
Has abstractyes

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