PMID- 30715258
OWN - NLM
STAT- MEDLINE
DCOM- 20200124
LR  - 20200124
IS  - 1876-4479 (Electronic)
IS  - 1873-9946 (Linking)
VI  - 13
IP  - 7
DP  - 2019 Jul 25
TI  - Ustekinumab Exposure-outcome Analysis in Crohn's Disease Only in Part Explains 
      Limited Endoscopic Remission Rates.
PG  - 864-872
LID - 10.1093/ecco-jcc/jjz008 [doi]
AB  - BACKGROUND AND AIMS: 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: 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: 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 mug/g] to w4 [529.0 mug/g] and w8 [372.2 mug/g], but increased again by w16 
      [537.4 mug/g] and w24 [749.0 mug/g]. A clear exposure-response relationship was 
      observed, both during induction and during maintenance therapy, with different 
      thresholds depending on the targeted outcome. 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.
CI  - Copyright (c) 2019 European Crohn's and Colitis Organisation (ECCO). Published by 
      Oxford University Press. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Verstockt, Bram
AU  - Verstockt B
AD  - Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU 
      Leuven, Leuven, Belgium.
AD  - Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, 
      Belgium.
FAU - Dreesen, Erwin
AU  - Dreesen E
AD  - Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, 
      Belgium.
FAU - Noman, Maja
AU  - Noman M
AD  - Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU 
      Leuven, Leuven, Belgium.
FAU - Outtier, An
AU  - Outtier A
AD  - Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU 
      Leuven, Leuven, Belgium.
FAU - Van den Berghe, Nathalie
AU  - Van den Berghe N
AD  - Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, 
      Belgium.
FAU - Aerden, Isolde
AU  - Aerden I
AD  - Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU 
      Leuven, Leuven, Belgium.
FAU - Compernolle, Griet
AU  - Compernolle G
AD  - Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, 
      Belgium.
FAU - Van Assche, Gert
AU  - Van Assche G
AD  - Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU 
      Leuven, Leuven, Belgium.
AD  - Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, 
      Belgium.
FAU - Gils, Ann
AU  - Gils A
AD  - Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, 
      Belgium.
FAU - Vermeire, Severine
AU  - Vermeire S
AD  - Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU 
      Leuven, Leuven, Belgium.
AD  - Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, 
      Belgium.
FAU - Ferrante, Marc
AU  - Ferrante M
AD  - Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU 
      Leuven, Leuven, Belgium.
AD  - Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, 
      Belgium.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Crohns Colitis
JT  - Journal of Crohn's & colitis
JID - 101318676
RN  - 0 (Biomarkers)
RN  - 0 (Leukocyte L1 Antigen Complex)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - FU77B4U5Z0 (Ustekinumab)
SB  - IM
MH  - Adult
MH  - Belgium
MH  - Biomarkers/analysis
MH  - C-Reactive Protein/analysis
MH  - Crohn Disease/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - *Endoscopy, Gastrointestinal
MH  - Female
MH  - Humans
MH  - Leukocyte L1 Antigen Complex/analysis
MH  - Male
MH  - Middle Aged
MH  - Pain Measurement
MH  - Prospective Studies
MH  - Remission Induction
MH  - Ustekinumab/administration & dosage/*therapeutic use
OTO - NOTNLM
OT  - Crohn's disease
OT  - Ustekinumab
OT  - calprotectin
OT  - endoscopic remission
OT  - real life
OT  - therapeutic drug monitoring
EDAT- 2019/02/05 06:00
MHDA- 2020/01/25 06:00
CRDT- 2019/02/05 06:00
PHST- 2018/11/27 00:00 [received]
PHST- 2018/12/30 00:00 [revised]
PHST- 2019/02/05 06:00 [pubmed]
PHST- 2020/01/25 06:00 [medline]
PHST- 2019/02/05 06:00 [entrez]
AID - 5304542 [pii]
AID - 10.1093/ecco-jcc/jjz008 [doi]
PST - ppublish
SO  - J Crohns Colitis. 2019 Jul 25;13(7):864-872. doi: 10.1093/ecco-jcc/jjz008.