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J Crohns Colitis. 2018 May 25;12(6):653-661. doi: 10.1093/ecco-jcc/jjy003.

Anti-TNF Therapeutic Drug Monitoring in Postoperative Crohn's Disease.

Author information

1
Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia.
2
Department of Research and Development, Prometheus Laboratories, Inc., San Diego, California, USA.
3
Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia.
4
Monash University, School of Public Health and Preventative Medicine, Melbourne, Australia.
5
Centre for Inflammatory Bowel Diseases, Fremantle Hospital and The University of Western Australia, Fremantle, Australia.
6
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital and University of Adelaide, Adelaide, Australia.
7
Department of Gastroenterology and Hepatology, Flinders Medical Centre and Flinders University, Adelaide, Australia.
8
Department of Gastroenterology, Alfred Health, Melbourne, Australia.
9
Department of Gastroenterology, Mater Health Services, University of Queensland Brisbane, Australia.
10
Department of Gastroenterology, Alfred Health and Monash University, Melbourne, Australia.
11
Melbourne Gastrointestinal Investigation Unit, Cabrini Hospital, Melbourne, Australia.
12
Department of Colorectal Medicine and Genetics, and Department of Medicine, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia.
13
Department of Gastroenterology, Bankstown Hospital, Sydney, Australia.
14
Department of Gastroenterology, Western Hospital, Melbourne, Australia.
15
Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, Australia.
16
IBD Group Queensland Institute of Medical Research, University of Queensland, Brisbane, Australia.
17
Department of Medicine, University of Otago, Christchurch, New Zealand.
18
AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia.

Abstract

Background:

Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence.

Methods:

As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months.

Results:

Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts ≥ i2] [9.98µg/mL vs 8.43 µg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 µg/mL] than patients on combination therapy [11.725 µg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 µg/mL vs 12.0 µg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046].

Conclusion:

Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.

PMID:
29385469
DOI:
10.1093/ecco-jcc/jjy003
[Indexed for MEDLINE]

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