Ustekinumab Exposure-outcome Analysis in Crohn's Disease Only in Part Explains Limited Endoscopic Remission Rates.
Adult
Belgium
Biomarkers
/ analysis
C-Reactive Protein
/ analysis
Crohn Disease
/ drug therapy
Dose-Response Relationship, Drug
Endoscopy, Gastrointestinal
Female
Humans
Leukocyte L1 Antigen Complex
/ analysis
Male
Middle Aged
Pain Measurement
Prospective Studies
Remission Induction
Ustekinumab
/ administration & dosage
Crohn’s disease
Ustekinumab
calprotectin
endoscopic remission
real life
therapeutic drug monitoring
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
25 Jul 2019
25 Jul 2019
Historique:
received:
27
11
2018
revised:
30
12
2018
pubmed:
5
2
2019
medline:
25
1
2020
entrez:
5
2
2019
Statut:
ppublish
Résumé
Ustekinumab, an anti-IL12/23p40 monoclonal antibody, has been approved for Crohn's disease [CD]. Real-life data in CD patients receiving ustekinumab intravenously [IV] during induction, followed by subcutaneous [SC] maintenance, are lacking. We assessed efficacy of ustekinumab and studied exposure-response correlations. We performed a prospective study in 86 CD patients predominantly refractory or intolerant to anti-tumour necrosis factor agents and/or vedolizumab. All received ustekinumab 6 mg/kg IV induction, with 90 mg SC every 8 weeks thereafter. Endoscopic response (50% decrease in Simple Endoscopic Score for CD [SES-CD] at Week 24), endoscopic remission [SES-CD ≤2], and clinical remission [daily stool frequency ≤2.8 and abdominal pain score ≤1] were assessed at weeks 4,8,16, and 24. Further serial analyses included patient-reported outcomes [PRO2], faecal calprotectin [fCal], and ustekinumab serum levels. SES-CD decreased from 11.5 [8.0-18.0] at baseline to 9.0 [6.0-16.0] at week [w]24 [p = 0.0009], but proportions of patients achieving endoscopic response [20.5%] or endoscopic remission [7.1%] were low. Clinical remission rates were 39.5% at w24. After IV induction, fCal dropped from baseline [1242.9 μg/g] to w4 [529.0 μg/g] and w8 [372.2 μg/g], but increased again by w16 [537.4 μg/g] and w24 [749.0 μg/g]. A clear exposure-response relationship was observed, both during induction and during maintenance therapy, with different thresholds depending on the targeted outcome. In this cohort of refractory CD patients, ustekinumab showed good clinical remission rates but limited endoscopic remission after 24 weeks. Our data suggest that higher doses may be required to achieve better endoscopic outcomes.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Ustekinumab, an anti-IL12/23p40 monoclonal antibody, has been approved for Crohn's disease [CD]. Real-life data in CD patients receiving ustekinumab intravenously [IV] during induction, followed by subcutaneous [SC] maintenance, are lacking. We assessed efficacy of ustekinumab and studied exposure-response correlations.
METHODS
METHODS
We performed a prospective study in 86 CD patients predominantly refractory or intolerant to anti-tumour necrosis factor agents and/or vedolizumab. All received ustekinumab 6 mg/kg IV induction, with 90 mg SC every 8 weeks thereafter. Endoscopic response (50% decrease in Simple Endoscopic Score for CD [SES-CD] at Week 24), endoscopic remission [SES-CD ≤2], and clinical remission [daily stool frequency ≤2.8 and abdominal pain score ≤1] were assessed at weeks 4,8,16, and 24. Further serial analyses included patient-reported outcomes [PRO2], faecal calprotectin [fCal], and ustekinumab serum levels.
RESULTS
RESULTS
SES-CD decreased from 11.5 [8.0-18.0] at baseline to 9.0 [6.0-16.0] at week [w]24 [p = 0.0009], but proportions of patients achieving endoscopic response [20.5%] or endoscopic remission [7.1%] were low. Clinical remission rates were 39.5% at w24. After IV induction, fCal dropped from baseline [1242.9 μg/g] to w4 [529.0 μg/g] and w8 [372.2 μg/g], but increased again by w16 [537.4 μg/g] and w24 [749.0 μg/g]. A clear exposure-response relationship was observed, both during induction and during maintenance therapy, with different thresholds depending on the targeted outcome.
CONCLUSIONS
CONCLUSIONS
In this cohort of refractory CD patients, ustekinumab showed good clinical remission rates but limited endoscopic remission after 24 weeks. Our data suggest that higher doses may be required to achieve better endoscopic outcomes.
Identifiants
pubmed: 30715258
pii: 5304542
doi: 10.1093/ecco-jcc/jjz008
doi:
Substances chimiques
Biomarkers
0
Leukocyte L1 Antigen Complex
0
C-Reactive Protein
9007-41-4
Ustekinumab
FU77B4U5Z0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
864-872Informations de copyright
Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.