Real-world Endoscopic and Histological Outcomes Are Correlated with Ustekinumab Exposure in Patients with Ulcerative Colitis.
Ustekinumab
endoscopic remission
exposure-response
histologic remission
real-world
therapeutic drug monitoring
ulcerative colitis
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:
01 Nov 2022
01 Nov 2022
Historique:
received:
15
03
2022
revised:
19
04
2022
accepted:
05
05
2022
pubmed:
10
5
2022
medline:
4
11
2022
entrez:
9
5
2022
Statut:
ppublish
Résumé
Histo-endoscopic outcomes are being proposed as new treatment targets in ulcerative colitis [UC]. Little is known about the pharmacokinetic-pharmacodynnamic [PK-PD] relationship of ustekinumab [UST] in UC patients or whether serum UST concentrations reflect tissue drug exposure. We aimed to study UST serum concentrations and their relation to tissue exposure and drug effectiveness in a real-world setting. A total of 42 UC patients starting UST were prospectively followed by clinical, endoscopic and histological assessments at Week 16. Histological remission was defined as Nancy Histology Index of 0. Analogous to the UNIFI programme, histo-endoscopic mucosal improvement was defined as a combination of histological improvement [Geboes ≤3.1] and endoscopic improvement [MES ≤1]. Paired trough serum samples and colonic mucosal biopsies were collected for UST levels measurement. After 16 weeks [IQR 15.8-16.4] of therapy, histological remission and histo-endoscopic mucosal improvement were observed in 19 [45%] and 18 [43%] patients, respectively. Patients who achieved these outcomes had higher serum UST levels than those who did not. Patients with shorter disease duration and clinical response at Week 8 had higher odds to achieve histological remission. UST concentrations from paired serum and biopsy samples revealed a strong positive correlation [r = 0.88, p < 0.001], in both inflamed and uninflamed tissue. In this real-world cohort of refractory UC patients initiating UST, more than a third of the patients achieved histological remission. A drug exposure-response relationship was observed for histo-endoscopic outcomes, with no added value of measuring tissue exposure given the strong correlation with serum exposure.
Sections du résumé
BACKGROUND
BACKGROUND
Histo-endoscopic outcomes are being proposed as new treatment targets in ulcerative colitis [UC]. Little is known about the pharmacokinetic-pharmacodynnamic [PK-PD] relationship of ustekinumab [UST] in UC patients or whether serum UST concentrations reflect tissue drug exposure. We aimed to study UST serum concentrations and their relation to tissue exposure and drug effectiveness in a real-world setting.
METHODS
METHODS
A total of 42 UC patients starting UST were prospectively followed by clinical, endoscopic and histological assessments at Week 16. Histological remission was defined as Nancy Histology Index of 0. Analogous to the UNIFI programme, histo-endoscopic mucosal improvement was defined as a combination of histological improvement [Geboes ≤3.1] and endoscopic improvement [MES ≤1]. Paired trough serum samples and colonic mucosal biopsies were collected for UST levels measurement.
RESULTS
RESULTS
After 16 weeks [IQR 15.8-16.4] of therapy, histological remission and histo-endoscopic mucosal improvement were observed in 19 [45%] and 18 [43%] patients, respectively. Patients who achieved these outcomes had higher serum UST levels than those who did not. Patients with shorter disease duration and clinical response at Week 8 had higher odds to achieve histological remission. UST concentrations from paired serum and biopsy samples revealed a strong positive correlation [r = 0.88, p < 0.001], in both inflamed and uninflamed tissue.
CONCLUSIONS
CONCLUSIONS
In this real-world cohort of refractory UC patients initiating UST, more than a third of the patients achieved histological remission. A drug exposure-response relationship was observed for histo-endoscopic outcomes, with no added value of measuring tissue exposure given the strong correlation with serum exposure.
Identifiants
pubmed: 35533353
pii: 6582859
doi: 10.1093/ecco-jcc/jjac067
doi:
Substances chimiques
Ustekinumab
FU77B4U5Z0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1562-1570Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.