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Record W4386318621 · doi:10.1053/j.gastro.2023.08.038

Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study

2023· article· en· W4386318621 on OpenAlexaff
Laurent Peyrin‐Biroulet, Jessica R. Allegretti, David T. Rubin, Brian Bressler, Matthew Germinaro, Kuan‐Hsiang Gary Huang, Nicole Shipitofsky, Hongyan Zhang, Rebbecca Wilson, Chenglong Han, Brian G. Feagan, William J. Sandborn, Julián Panés, Tadakazu Hisamatsu, Gary R. Lichtenstein, Bruce E. Sands, Axel Dignaß, О. Аbrahamovych, Halyna Afanasieva, Lilia Aitova, Engin Altıntaşž, Romain Altwegg, П. С. Андреев, Kazuki Aomatsu, Monika Augustyn, Paola Balestrieri, Jakob Begun, Luciana Soledad Brunatto, Diego Bulgheroni, Elena Bunkova, Mercedes Cabello, Qian Cao, Flavio Caprioli, Rute Cerqueira, Baili Chen, Chou‐Chen Chen, Chou-Pin Chen, Cheng‐Tang Chiu, Chang Hwan Choi, Michele Cicala, Olena Datsenko, Pieter Dewint, Eugeni Domènech, Joris Dutré, George Duvall, J. C. Fernández, Rafał Filip, Ronald Fogel, Sharyle Fowler, Toshimitsu Fujii, Masayuki Fukata, Yohei Furumoto, Antonio Gasbarrini, Beata Gawdis-Wojnarska, Cyrielle Gilletta, Paolo Gionchetti, Eran Goldin, Oleksandr Golovchenko, Maciej Gonciarz, Can Gönen, Gaston Gonzalez Segura, Oleksii Gridnyev, T Gyökeres, Xavier Hébuterne, Charlotte Hedin, Per M. Hellström, Ida Hilmi, Ivo Horný, Gyula Horvat, Namiko Hoshi, Luděk Hrdlička, Shunji Ishihara, Olha Ivanishyn, Byung Ik Jang, Takashi Kagaya, Shuji Kanmura, Marina Karakina, Nakai Katsuhiko, Jarosław Kierkuś, Hyo Jong Kim, Young‐Ho Kim, G Kiss, Jochen Klaus, D Kleczkowski, Maria Kłopocka, Taku Kobayashi, Iwona Kobielusz‐Gembala, Ja Seol Koo, Adam Kopoń, Tetiana Kravchenko, Masatoshi Kudo, Kwang An Kwon, Paula Lago, David Laharie, Ian C. Lawrance, Jarosław Leszczyszyn, Yan Li, Milan Lukáš, Christian Maaser, Atsuo Maemoto, Hiroyuki Marusawa, Matthew J. McBride, Shoba Mendu, Pál Miheller, Hideharu Miyabayashi, Wolfgang Mohl, Gregory Moore, Satoshi Motoya, Narayanachar Murali, Mohammed Al Naem, Koichi Nakajima, Yasunari Nakamoto, Stéphane Nancey, Joaquim Isquierdo Quadrado Neto, Michio Onizawa, Yohei Ono, Taro Osada, М. Ф. Осипенко, Danuta Owczarek, Bhaktasharan Patel, Kamal Patel, Elina Petrova, Е Г Порошина, Francisco Portela, Lyudmyla Prystupa, Xavier Roblin, Jacek Romatowski, Grażyna Rydzewska, Simone Saibeni, Hirotake Sakuraba, Mark Samaan, Michael Schultz, J Schulze, Shahriar Sedghi, Ursula Seidler, Sung Jae Shin, Mykola Stanislavchuk, David Stokesberry, Takayoshi Suzuki, Hiroki Taguchi, Lyudmila Tankova, Lena Thin, Tkachev Av, Leyanira Torrealba, Nataliia Tsarynna, Zsolt Tulassay, Tetsuya Ueo, Ekaterina Valuyskikh, Olga Vasilevskaya, Manuel Viamonte, Shu‐Chen Wei, Roni Weisshof, Katarzyna Wójcik‐Pszczoła, Byong Duk Ye, Hsu‐Heng Yen, Hyuk Yoon, Kosuke Yoshida, Andriy Yurkiv, Osamu Zaha, Qiang Zhan

Bibliographic record

VenueGastroenterology · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsWestern UniversityUniversity of British ColumbiaMcGill University Health Centre
FundersJanssen Research and DevelopmentJanssen Scientific Affairs
KeywordsMedicinePlaceboClinical endpointInternal medicineGastroenterologyUlcerative colitisClinical trialSurgery

Abstract

fetched live from OpenAlex

Background & AimsThe QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy.MethodsIn this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12. Guselkumab and placebo week-12 clinical nonresponders received subcutaneous or intravenous guselkumab 200 mg, respectively, at weeks 12/16/20 (uncontrolled study period).ResultsThe primary analysis population included patients with baseline modified Mayo scores ≥5 and ≤9 (intravenous guselkumab 200 mg, n = 101; 400 mg, n = 107; placebo, n = 105). Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) vs placebo (27.6%; both P < .001). Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24. Safety was similar among guselkumab and placebo groups.ConclusionsGuselkumab intravenous induction was effective vs placebo in patients with moderately to severely active UC. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups. ClinicalTrials.gov number: NCT04033445. The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy. In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12. Guselkumab and placebo week-12 clinical nonresponders received subcutaneous or intravenous guselkumab 200 mg, respectively, at weeks 12/16/20 (uncontrolled study period). The primary analysis population included patients with baseline modified Mayo scores ≥5 and ≤9 (intravenous guselkumab 200 mg, n = 101; 400 mg, n = 107; placebo, n = 105). Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) vs placebo (27.6%; both P < .001). Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24. Safety was similar among guselkumab and placebo groups. Guselkumab intravenous induction was effective vs placebo in patients with moderately to severely active UC. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups. ClinicalTrials.gov number: NCT04033445.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.235
Threshold uncertainty score0.818

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 head0.010
GPT teacher head0.260
Teacher spread0.250 · 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 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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Citations92
Published2023
Admission routes1
Has abstractyes

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