ABSTRACT
With the overspread use of measurement of serum levels of anti-tumor necrosis factor (TNF) agents (therapeutic drug monitoring, TDM), new therapeutic strategies have been used in the management of Crohn’s disease (CD). Different targets are correlated with increased levels of circulating drugs. Recent evidence demonstrated that higher serum levels of anti-TNF agents may be associated to better outcomes in perianal fistulizing CD (PFCD). Overall, patients with healed fistulas had higher serum levels of infliximab and adalimumab as compared to those with active drainage. This was demonstrated in some cohort studies, in induction and maintenance, in adults and children with PFCD. In this narrative review, authors summarize current evidence on the use of serum level measurement of anti-TNF agents and its correlation with perianal fistula healing in CD patients. Data on the use of TDM in PFCD is discussed in detail. The retrospective design of the studies and the lack of objective parameters to measure fistula healing are the main limitations of published data. Prospective studies, with central reading of objective radiological parameters, such as pelvic magnetic resonance imaging scores, can improve the level of evidence on the possible advantages of TDM in perianal fistula in CD and are warranted.
ABSTRACT
With the overspread use of measurement of serum levels of anti-tumor necrosis factor (TNF) agents (therapeutic drug monitoring, TDM), new therapeutic strategies have been used in the management of Crohn’s disease (CD). Different targets are correlated with increased levels of circulating drugs. Recent evidence demonstrated that higher serum levels of anti-TNF agents may be associated to better outcomes in perianal fistulizing CD (PFCD). Overall, patients with healed fistulas had higher serum levels of infliximab and adalimumab as compared to those with active drainage. This was demonstrated in some cohort studies, in induction and maintenance, in adults and children with PFCD. In this narrative review, authors summarize current evidence on the use of serum level measurement of anti-TNF agents and its correlation with perianal fistula healing in CD patients. Data on the use of TDM in PFCD is discussed in detail. The retrospective design of the studies and the lack of objective parameters to measure fistula healing are the main limitations of published data. Prospective studies, with central reading of objective radiological parameters, such as pelvic magnetic resonance imaging scores, can improve the level of evidence on the possible advantages of TDM in perianal fistula in CD and are warranted.
ABSTRACT
BACKGROUND/AIMS: Lipopolysaccharide (LPS) is a molecule formed by lipids and polysaccharides and is the major cell wall component of gram-negative bacteria. High LPS levels are known to block CD26 expression by activating Toll-like receptor 4. The aim of this study was to correlate the serum levels of LPS and CD26 in Crohn's disease (CD) patients with serum levels of C-reactive protein (CRP), interleukins, CD activity index, and tumor necrosis factor-α (TNF-α). METHODS: Serum samples were collected from 27 individuals (10 with active CD, 10 with inactive CD, and 7 controls) and the levels of LPS, CD26, TNF-α, interleukin-1β (IL-1β), IL-6, IL-17, and CRP were determined by enzyme-linked immunosorbent assay. The levels of LPS and CD26 were then tested for correlation with TNF-α, IL-1β, IL-6, IL-17, and CRP. RESULTS: Serum levels of LPS were significantly elevated in the active CD group (P=0.003). Levels of IL-1β (P=0.002), IL-6 (P=0.003), and IL-17 (P<0.001) were lower in the CD groups. Serum TNF-α levels were increased in the active CD group. The CRP levels were elevated in the CD groups when compared to controls (P<0.001). The CD26 levels were lower in the CD groups than in the control group (P<0.001). Among the variables analyzed, there was a correlation between LPS and CRP (r=−0.53, P=0.016) in the CD groups. CONCLUSIONS: Individuals with CD exhibited higher serum levels of LPS varying from a 2- to 6-fold increase depending on disease activity, when compared with healthy controls. CD26 levels were lower in the CD groups. Both LPS and CD26 correlated with disease severity and serve as potential CD biomarkers.
Subject(s)
Humans , Biomarkers , C-Reactive Protein , Cell Wall , Crohn Disease , Enzyme-Linked Immunosorbent Assay , Gram-Negative Bacteria , Inflammatory Bowel Diseases , Interleukin-17 , Interleukin-6 , Interleukins , Lipopolysaccharides , Necrosis , Polysaccharides , Toll-Like Receptor 4ABSTRACT
Recent advances in medical and surgical therapy were achieved during the last two decades in the management of Crohn's disease (CD). Anti-tumor necrosis factor (anti-TNF) agents are widely used worldwide. However, a significant proportion of patients still need surgical resections. The impact of previous exposure to these agents on the perioperative and postoperative outcomes is still controversial. In this critical review, we aimed to position the strategy of intentional preoperative use of anti-TNF agents in the management of CD. The indications and contraindications for this strategy are detailed, and despite scarce evidence, the possible advantages and disadvantages of the intentional use of anti-TNF agents before abdominal surgery in CD are discussed.
Subject(s)
Humans , Crohn Disease , Necrosis , Preoperative Care , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND/AIMS: Postoperative endoscopic recurrence (PER) occurs in nearly 80% of patients 1 year after ileocecal resection in patients with Crohn's disease (CD). Biological agents were more effective in reducing the rates of PER in comparison with conventional therapy, in prospective trials. The aim of this study was to compare the PER rates of biological versus conventional therapy after ileocecal resections in patients with CD in real-world practice. METHODS: The MULTIPER (Multicenter International Postoperative Endoscopic Recurrence) database is a retrospective analysis of PER rates in CD patients after ileocecal resection, from 7 referral centers in 3 different countries. All consecutive patients who underwent ileocecal resections between 2008 and 2012 and in whom colonoscopies had been performed up to 12 months after surgery, were included. Recurrence was defined as Rutgeerts' score > or =i2. The patients were allocated to either biological or conventional therapy after surgery, and PER rates were compared between the groups. RESULTS: Initially, 231 patients were evaluated, and 63 were excluded. Of the 168 patients in the database, 96 received anti-tumor necrosis factor agents and 72 were treated with conventional therapy after resection. The groups were comparable regarding age, gender, and perianal disease. There was longer disease duration, more previous resections, and more open surgical procedures in patients on biologicals postoperatively. PER was identified in 25/96 (26%) patients on biological therapy and in 24/72 (33.3%) patients on conventional therapy (P=0.310). CONCLUSIONS: In this retrospective observational analysis from an international database, no difference was observed between biological and conventional therapy in preventing PER after ileocecal resections in CD patients.
Subject(s)
Humans , Biological Factors , Biological Therapy , Colonoscopy , Crohn Disease , Necrosis , Observational Study , Recurrence , Referral and Consultation , Retrospective Studies , Tumor Necrosis Factor-alphaABSTRACT
In most patients, postoperative endoscopic recurrence (PER) occurs 1 year after abdominal resection for Crohn's disease (CD). Preventing PER is essential for disease control, as most patients develop further clinical and surgical recurrences. Conventional therapy with nitroimidazoles, aminosalicylates, and immunomodulators have limited efficacy for preventing PER. Initial trials with biological therapy (infliximab and adalimumab) showed promising results in preventing PER, and the efficacy of these drugs seems higher than that with conventional therapy. The aim of this review is to outline the results of studies that used infliximab or adalimumab for preventing and treating PER in CD patients. Data with both agents are available, and a few, small prospective trials have shown the efficacy of these drugs in patients with a high risk for recurrence. We believe that, in 2013, biological agents will be better accepted for the prevention PER in CD patients, in addition to the already existing data. Larger trials are still underway, and their results will certainly determine the role of these agents in PER, which develops after bowel resection for CD.