MétaCan
Menu
← Back to cohort

S807 Corticosteroid-Sparing Effects of Ustekinumab Therapy for Ulcerative Colitis Through 4 Years: UNIFI Long-Term Extension

2022· article· en· W4316081592 on OpenAlexaff
María T. Abreu, Ellen Scherl, David Rowbotham, Silvio Danese, William J. Sandborn, Miao Ye, Hongyan Zhang, Remo Panaccione, Waqqas Afif, Tadakazu Hisamatsu, Rupert W. Leong, Bruce E. Sands, Ramesh Arasaradnam, Colleen Marano

Bibliographic record

VenueThe American Journal of Gastroenterology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsMcGill University Health CentreUniversity of Calgary
Fundersnot available
KeywordsMedicinePlaceboUstekinumabUlcerative colitisMaintenance therapyInternal medicineClinical endpointRandomizationGastroenterologyCorticosteroidColonoscopyClinical trialSurgeryDiseaseColorectal cancerChemotherapyAdalimumab

Abstract

fetched live from OpenAlex

Introduction: Ustekinumab (UST) is an IL-12/23p40 inhibitor approved for treatment of Crohn’s disease and ulcerative colitis (UC). In the UNIFI maintenance study of patients (pts) with moderate to severe UC, > 90% of pts who achieved clinical response or remission at week (wk) 44 were not receiving corticosteroids, an important therapeutic goal. In this analysis, we describe the corticosteroid-sparing effects of UST treatment through 4 years (yrs) among pts who were treated in the UNIFI long-term extension (LTE). Methods: Overall, 523 intravenous UST induction responders were randomized to subcutaneous (SC) maintenance therapy (placebo [PBO], n=175; UST 90mg every 12 wks [q12w], n=172; or UST 90mg q8w, n=176). A total of 284 UST pts completed wk44 and were treated in the LTE. PBO pts were discontinued after study unblinding. Based on investigator’s clinical judgement of UC disease activity, pts in the LTE were eligible to receive a dose adjustment starting at wk56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Pts in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Efficacy was evaluated using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0). During the maintenance study, all pts receiving corticosteroids at maintenance baseline were required to initiate tapering. Through wk200 of the LTE, symptomatic remission endpoints were calculated with treatment failure and missing data nonresponder imputation, and dose adjustment was not considered to be a treatment failure. Missing corticosteroid dose data were managed using last observation carried forward. Results: Of the 284 pts randomized to UST and treated in the LTE, 139 were receiving corticosteroids at maintenance baseline. Of these, 79.1% (n=110) were no longer receiving corticosteroids at wk200. Rates of corticosteroid-free symptomatic remission at wk200 were generally similar for the q8w and q12w maintenance doses (Table). Of the UST-treated pts in symptomatic remission at wk200, 94/96 (97.9%) in the q12w group and 91/96 (94.8%) in the q8w group were corticosteroid free. Conclusion: UST maintenance therapy, with both q8w and q12w dosing regimens, was effective in reducing and eliminating the use of corticosteroids in pts with UC through 4 yrs. The majority of pts in symptomatic remission were corticosteroid free through 4 yrs of treatment with UST. Table 1. - Symptomatic remission and corticosteroid-sparing effects in patients who were randomized to UST in maintenance and were treated in the long-term extension Analysis 90 mg UST SC q12w a 90 mg UST SC q8w a Combined UST a Randomized patients in maintenance who were treated in the LTE, N 141 143 284 Patients in symptomatic remission, n/N (%) d,e,f Week 44 117/141 (83.0) 119/143 (83.2) 236/284 (83.1) Week 200 96/141 (68.1) 96/143 (67.1) 192/284 (67.6) Patients in symptomatic remission and not receiving corticosteroids, n/N (%) b,d,e,f Week 44 111/141 (78.7) 115/143 (80.4) 226/284 (79.6) Week 200 94/141 (66.7) 91/143 (63.6) 185/284 (65.1) Patients in symptomatic remission and not receiving corticosteroids among patients receiving corticosteroids at maintenance baseline, n/N (%) b,c,d,e,f Week 44 49/68 (72.1) 56/71 (78.9) 105/139 (75.5) Week 200 39/68 (57.4) 47/71 (66.2) 86/139 (61.9) Patients who were able to eliminate the use of corticosteroids, n/N (%) b,c Week 44 61/68 (89.7) 64/71 (90.1) 125/139 (89.9) Week 200 53/68 (77.9) 57/71 (80.3) 110/139 (79.1) LTE, long-term extension; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; UST, ustekinumab.aRandomized group at maintenance Week 0 regardless of whether patients had a dose adjustment during the LTE.bPatients who had a missing value in corticosteroid use at the designated visit had their last available value carried forward to the designated visit.cDenominator is the number of patients who were receiving concomitant corticosteroids at maintenance baseline.dSymptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0.ePatients who had both stool frequency and rectal bleeding subscores missing at a visit were considered not to be in symptomatic remission for that visit.fPatients who had an ostomy or colectomy, or discontinued study agent due to lack of therapeutic effect or due to an adverse event of worsening of ulcerative colitis prior to the designated visit were considered not to be in symptomatic remission.

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)0.002
metaresearch head score (Gemma)0.001
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 score0.005
Threshold uncertainty score0.016

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0050.000

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 head0.258
Teacher spread0.249 · 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".

Quick stats

Citations0
Published2022
Admission routes1
Has abstractyes

Explore more

Same venueThe American Journal of Gastroenterology→Same topicInflammatory Bowel Disease→French-language works237,207→