PMID- 29623105
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220316
IS  - 1756-283X (Print)
IS  - 1756-2848 (Electronic)
IS  - 1756-283X (Linking)
VI  - 11
DP  - 2018
TI  - Subtherapeutic concentrations of infliximab and adalimumab are associated with 
      increased disease activity in Crohn's disease.
PG  - 1756284818759930
LID - 10.1177/1756284818759930 [doi]
LID - 1756284818759930
AB  - BACKGROUND: Low anti-tumor necrosis factor alpha (TNFalpha) serum concentrations may 
      result in lack of treatment response in patients with inflammatory bowel disease. 
      We determined the anti-TNFalpha drug concentrations in patients with inflammatory 
      bowel disease and investigated whether or not subtherapeutic drug concentrations 
      were associated with increased levels of disease activity. METHODS: In a 
      single-center cross-sectional study, we included patients with ulcerative colitis 
      or Crohn's disease who were receiving infliximab or adalimumab maintenance 
      therapy. Demographic data, disease activity symptom scores (Partial Mayo Score, 
      Harvey Bradshaw Index), inflammatory markers [C-reactive protein (CRP), fecal 
      calprotectin], antidrug antibodies and serum drug concentrations were recorded. 
      Therapeutic drug concentrations were defined as 3-8 mg/liter for infliximab and 
      5-12 mg/liter for adalimumab. RESULTS: Of 210 patients included, 137 (65.2%) had 
      Crohn's disease. In the adalimumab group, subtherapeutic drug concentrations were 
      measured in 16.7% of patients with ulcerative colitis and in 27.7% of patients 
      with Crohn's disease. In the infliximab group, subtherapeutic drug concentrations 
      were found in 23% (ulcerative colitis) and 30.3% (Crohn's disease) of patients. 
      In Crohn's disease, subtherapeutic adalimumab concentrations were associated with 
      higher fecal calprotectin and CRP concentrations compared with therapeutic 
      concentrations. Subtherapeutic infliximab concentrations in patients with Crohn's 
      disease were also associated with higher CRP concentrations compared with 
      therapeutic concentrations. CONCLUSIONS: The prevalence of subtherapeutic drug 
      levels ranged from 17% to 30%. In patients with Crohn's disease, subtherapeutic 
      serum drug concentrations were associated with significantly higher disease 
      activity with both anti-TNFalpha agents. These findings were not observed in patients 
      with ulcerative colitis. Clinicaltrials.gov identifier [NCT02134054].
FAU - Carlsen, Arne
AU  - Carlsen A
AUID- ORCID: 0000-0002-6005-6394
AD  - Stavanger University Hospital, PO Box 8100, 4068 Stavanger, Norway.
FAU - Omdal, Roald
AU  - Omdal R
AD  - Unit of Clinical Immunology, Department of Medicine, Stavanger University 
      Hospital, Stavanger, Norway.
FAU - Leitao, Kristian Ogreid
AU  - Leitao KO
AD  - Unit of Gastroenterology, Department of Medicine, Stavanger University Hospital, 
      Stavanger, Norway.
FAU - Isaksen, Kjetil
AU  - Isaksen K
AD  - Unit of Gastroenterology, Department of Medicine, Stavanger University Hospital, 
      Stavanger, Norway.
FAU - Hetta, Anne Kristine
AU  - Hetta AK
AD  - Unit of Gastroenterology, Department of Medicine, Stavanger University Hospital, 
      Stavanger, Norway.
FAU - Karlsen, Lars Normann
AU  - Karlsen LN
AD  - Unit of Gastroenterology, Department of Medicine, Stavanger University Hospital, 
      Stavanger, Norway.
FAU - Aabakken, Lars
AU  - Aabakken L
AD  - Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.
FAU - Bolstad, Nils
AU  - Bolstad N
AD  - Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
FAU - Warren, David
AU  - Warren D
AD  - Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
FAU - Lundin, Knut E A
AU  - Lundin KEA
AD  - Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.
FAU - Grimstad, Tore
AU  - Grimstad T
AD  - Unit of Gastroenterology, Department of Medicine, Stavanger University Hospital, 
      Stavanger, Norway.
LA  - eng
SI  - ClinicalTrials.gov/NCT02134054
PT  - Journal Article
DEP - 20180314
PL  - England
TA  - Therap Adv Gastroenterol
JT  - Therapeutic advances in gastroenterology
JID - 101478893
PMC - PMC5881967
OTO - NOTNLM
OT  - antitumor necrosis factor alpha
OT  - inflammatory bowel disease
OT  - serum concentrations
OT  - subtherapeutic
COIS- Conflict of interest statement: Arne Carlsen has served as speaker for Takeda AS 
      and Tillotts Pharma AB. Knut Lundin has served as speaker for Takeda AS and MSD. 
      Tore Grimstad has served as speaker for Ferring Pharmaceuticals, served as 
      consultant for Takeda AS and Janssen, and has received unrestricted research 
      grants from AbbVie AS and Tillotts Pharma AB. All other authors declare that 
      there is no conflict of interests.
EDAT- 2018/04/07 06:00
MHDA- 2018/04/07 06:01
PMCR- 2018/03/14
CRDT- 2018/04/07 06:00
PHST- 2017/10/24 00:00 [received]
PHST- 2018/01/24 00:00 [accepted]
PHST- 2018/04/07 06:00 [entrez]
PHST- 2018/04/07 06:00 [pubmed]
PHST- 2018/04/07 06:01 [medline]
PHST- 2018/03/14 00:00 [pmc-release]
AID - 10.1177_1756284818759930 [pii]
AID - 10.1177/1756284818759930 [doi]
PST - epublish
SO  - Therap Adv Gastroenterol. 2018 Mar 14;11:1756284818759930. doi: 
      10.1177/1756284818759930. eCollection 2018.