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Record W4214694674 · doi:10.1053/j.gastro.2022.02.033

Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results

2022· article· en· W4214694674 on OpenAlexaff
Julián Panés, Jean‐Frédéric Colombel, Geert D’Haens, Stefan Schreiber, Remo Panaccione, Laurent Peyrin‐Biroulet, Edward V. Loftus, Silvio Danese, Satoshi Tanida, Yusuke Okuyama, Édouard Louis, Alessandro Armuzzi, Marc Ferrante, Harald Vogelsang, Toshifumi Hibi∥, Mamoru Watanabe, J Lefèbvre, Tricia Finney‐Hayward, Yuri Sánchez González, Thao Doan, Nael M. Mostafa, Kimitoshi Ikeda, Wangang Xie, Bidan Huang, Joel Petersson, Jasmina Kalabic, Anne Robinson, William J. Sandborn

Bibliographic record

VenueGastroenterology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsUniversity of Calgary
FundersJanssen PharmaceuticalsSandozJohnson and JohnsonGenentechActive BiotechToray IndustriesShireKisseiOtsuka AmericaUCBTaiho PharmaceuticalEli Lilly and CompanyBoehringer Ingelheim EspañaCelgeneGilead SciencesAstraZeneca EspañaMedtronicTakeda Pharmaceutical CompanyAmgenSchering-PloughGlaxoSmithKline EspañaAbbVieAstellas Pharma USKaken PharmaceuticalNational Institute of Diabetes and Digestive and Kidney DiseasesKyowa Hakko KirinKyorin PharmaceuticalSanofiMerckAllerganSeres TherapeuticsRoche EspañaNippon KayakuPfizerBristol-Myers Squibb
KeywordsUlcerative colitisDosingMedicineAdalimumabInternal medicineMaintenance therapyChemotherapyTumor necrosis factor alpha

Abstract

fetched live from OpenAlex

BACKGROUND & AIMS: SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis) evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis. METHODS: This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18-75 years, full Mayo score 6-12, centrally read endoscopy subscore 2-3) were randomized 3:2 to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3) or standard induction regimen (160 mg at week 0 and 80 mg at week 2); all received 40 mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40 mg every week (ew), 40 mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40 mg ew or 40 mg eow maintenance regimens. RESULTS: In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen vs standard induction regimen achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P = .265); among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P = .069). In the integrated (main + Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (nominal P = .045). Safety profiles were comparable between dosing regimens. CONCLUSION: Although primary end points were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in ulcerative colitis. CLINICALTRIALS: gov, Number: NCT002209456.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.449
Threshold uncertainty score0.547

Codex and Gemma teacher scores by category

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

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 head0.014
GPT teacher head0.254
Teacher spread0.240 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
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".

Quick stats

Citations72
Published2022
Admission routes1
Has abstractyes

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