Rates, predictive factors and effectiveness of ustekinumab intensification to 4- or 6-weekly intervals in Crohn's disease.


Journal

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
ISSN: 1878-3562
Titre abrégé: Dig Liver Dis
Pays: Netherlands
ID NLM: 100958385

Informations de publication

Date de publication:
08 2023
Historique:
received: 12 07 2022
revised: 04 10 2022
accepted: 05 10 2022
medline: 28 7 2023
pubmed: 26 10 2022
entrez: 25 10 2022
Statut: ppublish

Résumé

The UNITI trial reports efficacy of ustekinumab (UST) dose intensification in Crohn's disease (CD) from 12- to 8-weekly, but not 4-weekly. We aimed 1) to assess the cumulative incidence of UST dose intensification to 4- or 6-weekly, 2) to identify factors associated with dose intensification, and 3) to assess the effectiveness of this strategy. We performed a retrospective, observational cohort study in NHS Lothian including all UST treated CD patients (2015-2020). 163 CD patients were treated with UST (median follow-up: 20.3 months [13.4-38.4]), of whom 55 (33.7%) underwent dose intensification to 4-weekly (n = 50, 30.7%) or 6-weekly (n = 5, 3.1%). After 1 year 29.9% were dose intensified. Prior exposure to both anti-TNF and vedolizumab (HR 9.5; 1.3-70.9), and concomitant steroid use at UST start (HR 1.8; 1.0-3.1) were associated with dose intensification. Following dose intensification, 62.6% patients (29/55) remained on UST beyond 1 year. Corticosteroid-free clinical remission was achieved in 27% at week 16 and 29.6% at last follow-up. One third of CD patients treated with UST underwent dose intensification to a 4- or 6-weekly interval within the first year. Patients who failed both anti-TNF and vedolizumab, or required steroids at initiation were more likely to dose intensify.

Sections du résumé

BACKGROUND
The UNITI trial reports efficacy of ustekinumab (UST) dose intensification in Crohn's disease (CD) from 12- to 8-weekly, but not 4-weekly. We aimed 1) to assess the cumulative incidence of UST dose intensification to 4- or 6-weekly, 2) to identify factors associated with dose intensification, and 3) to assess the effectiveness of this strategy.
METHODS
We performed a retrospective, observational cohort study in NHS Lothian including all UST treated CD patients (2015-2020).
RESULTS
163 CD patients were treated with UST (median follow-up: 20.3 months [13.4-38.4]), of whom 55 (33.7%) underwent dose intensification to 4-weekly (n = 50, 30.7%) or 6-weekly (n = 5, 3.1%). After 1 year 29.9% were dose intensified. Prior exposure to both anti-TNF and vedolizumab (HR 9.5; 1.3-70.9), and concomitant steroid use at UST start (HR 1.8; 1.0-3.1) were associated with dose intensification. Following dose intensification, 62.6% patients (29/55) remained on UST beyond 1 year. Corticosteroid-free clinical remission was achieved in 27% at week 16 and 29.6% at last follow-up.
CONCLUSION
One third of CD patients treated with UST underwent dose intensification to a 4- or 6-weekly interval within the first year. Patients who failed both anti-TNF and vedolizumab, or required steroids at initiation were more likely to dose intensify.

Identifiants

pubmed: 36283944
pii: S1590-8658(22)00734-4
doi: 10.1016/j.dld.2022.10.002
pii:
doi:

Substances chimiques

Ustekinumab FU77B4U5Z0
Dermatologic Agents 0

Types de publication

Observational Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1034-1041

Subventions

Organisme : Medical Research Council
ID : MR/S034919/1
Pays : United Kingdom

Informations de copyright

Copyright © 2022. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Conflict of interest Lauranne Derikx has served on an advisory board for Sandoz and as a speaker for Janssen. Spyros Siakavellas has received speaker fees from Pfizer and Janssen. Nikolas Plevris has served as a speaker for Janssen, Takeda and Pfizer. Beatriz Gros has served as a speaker for Abbvie and Galapagos. Colin Noble has served on an advisory board for Galapagos. Gareth-Rhys Jones has served as a speaker for Takeda, Janssen, Abbvie and Ferring. Charlie Lees has acted as a consultant to Abbvie, Janssen, Takeda, Pfizer, Galapagos, BMS, Pharmacosmos, GSK, Gilead, Topivert, Vifor Pharma, Celltrion, Dr Falk, Oshi Health, Trellus Health and Iterative Scopes; he has received speaking fees and travel support from Pfizer, Janssen, Abbvie, Galapagos, Fresnius Kabi, Takeda, Shire, Ferring, and Dr Falk. None of the other authors reported any conflicts of interest.

Auteurs

Lauranne A A P Derikx (LAAP)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK; Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands. Electronic address: Lauranne.Derikx@radboudumc.nl.

Nikolas Plevris (N)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK.

Shanna Su (S)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK.

Beatriz Gros (B)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK; Department of Gastroenterology and Hepatology, Reina Sofía University Hospital, Córdoba, Spain.

Mathew Lyons (M)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK.

Spyros I Siakavellas (SI)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK.

Nathan Constantine-Cooke (N)

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK; Centre for Genomics and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK.

Philip Jenkinson (P)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK.

Claire O'Hare (C)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK.

Colin Noble (C)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK.

Ian D Arnott (ID)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK.

Gareth-Rhys Jones (GR)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK; Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Scotland, UK.

Charlie W Lees (CW)

Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK; Centre for Genomics and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK.

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Classifications MeSH