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Record W4414039781 · doi:10.1055/s-0045-1810726

Efficacy and safety of risankizumab in patients with moderate to severe crohn’s disease: Results from the one-year SEQUENCE open-label Long-term extension

2025· article· en· W4414039781 on OpenAlexaff
Laurent Peyrin‐Biroulet, Raja Atreya, Silvio Danese, James O. Lindsay, John C. Chapman, Toni Anschutz, Xiu Huang, Javier Zambrano, Allan Platt, Namita Joshi, Raymond Cross

Bibliographic record

VenueZeitschrift für Gastroenterologie · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsMcGill University Health Centre
Fundersnot available
KeywordsCrohn's diseaseSequence (biology)Term (time)MedicineCrohn diseaseDiseaseExtension (predicate logic)Open labelPediatricsInternal medicineAdverse effectComputer sciencePhysicsChemistry

Abstract

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Background : Part 2 of the SEQUENCE study examines the long-term efficacy and safety of risankizumab (RZB), an IL-23 p19 inhibitor, in patients (pts) with moderate to severe Crohn’s disease (CD). We report the 1-year results from part 2 of the SEQUENCE study. Methods: In part 2 of SEQUENCE, pts randomized to the RZB arm who completed the week (wk) 48 visit could continue on open-label 360mg subcutaneous (SC) RZB maintenance dose every 8 wks (Q8w). [ 1 ] Pts with inadequate response during part 2 could receive rescue therapy (1x 600mg intravenous RZB, then 360mg RZB SC Q8w). Clinical remission (per CDAI and per stool frequency [SF]/abdominal pain score [APS]), steroid-free clinical remission, Inflammatory Bowel Disease Questionnaire [IBDQ] response, and IBDQ remission were assessed at wks 52 (baseline of OLE), 76, and 100. Data were assessed for all intent-to-treat (ITT) pts using as observed (AO) regardless of rescue therapy as well as per nonresponder imputation (NRI), where patients were categorised as nonresponders for visits with missing assessments, visits after premature discontinuation of study, and visits after initiation of rescue therapy. Treatment-emergent adverse events (TEAEs) reported on or after the first dose in part 2 were analysed Results: 224 pts entered part 2 of SEQUENCE. Among the ITT pts, clinical remission rates (AO) remained stable from wk52 to wk100 (CDAI: 75.3% [168/223] to 84.4% [141/167]; SF/APS: 71.2% [158/222] to 74.7% [124/166]) ([ Fig. 1 ]). Most pts who achieved clinical remission were not receiving steroids at the corresponding visits ([ Fig. 2 ]). Pts also demonstrated sustained and clinically meaningful improvements in IBDQ response (86.7% [157/181]; AO) and IBDQ remission (65.3% [126/193]; AO) at wk100 ([ Fig. 1 ]). Similar results to AO were observed per NRI ([ Fig. 2 ]). 16 (7.1%) pts received rescue therapy during part 2, of which 77.8% (7/9) achieved wk100 clinical remission (AO). TEAEs and TEAEs of safety interest were consistent with the known safety profile of RZB. Adjudicated major cardiovascular adverse events, malignancies, serious infections and hepatic events remained stable with no new safety risks identified ([ Table 1 ]). [ 2 ] [ 3 ] No deaths occurred during the OLE. Fig. 1 Fig. 2 Table 1 Treatment-Emergent Adverse Events (TEAEs) 600 mg IV/360 mg SC RZB (N=262) n (%) Overall TEAE Any TEAE 243 (92.7) TEAE related to study drug according to the investigator 87 (33.2) Severe TEAE 65 (24.8) Serious TEAE 47 (17.9) TEAE leading to discontinuation study drug 15 (5.7) Death 0 TEAE of safety interest Adjudicated MACE events 0 Serious infections 17 (2.9) Opportunistic infections excluding tuberculosis and herpes zoster 2 (0.3) Malignant tumours 4 (0.7) Herpes zoster 3 (0.5) Non-melanoma skin cancer (NMSC) 2 (0.3) Hypersensitivity 52 (8.8) Hepatic events 36 (6.1) Injection site reactions 13 (2.2) E, events; CTE, continuous trial extension; MACE, major adverse cardiovascular event; NMSC, non-melanoma skin cancer; OLE, open-label extension; PY, patient-years; RZB, risankizumab; TEAE, treatment-emergent adverse event. E/100PYs=Events per 100 patient-years. Safety summary includes all patients who received at least one dose of study drug during OLE. TEAEs during OLE were defined as events that begin either on or after the first dose of the study drug and within 140 days after the last dose of study drug in OLE for patients who do not participate in CTE or until first dose of CTE if the patient is enrolled into CTE. Conclusion: Pts who received 100 wks of continuous RZB therapy in SEQUENCE demonstrated durable clinical efficacy and quality of life benefits. The safety profile is consistent with the known safety profile of RZB and supports long-term RZB treatment. Publication History Article published online: 04 September 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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 score0.016

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0010.003
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 head0.020
GPT teacher head0.282
Teacher spread0.262 · 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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Published2025
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