scholarly journals P734 Should we have a higher threshold for anti-TNF serum levels in Crohn’s disease patients with perianal disease?

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S589-S589
Author(s):  
C Arieira ◽  
F Dias de Castro ◽  
T Cúrdia Gonçalves ◽  
M J Moreira ◽  
J Cotter
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Perianal Fistula ◽  
Serum Levels ◽  
Perianal Disease ◽  
Serum Concentrations ◽  
Fistula Closure ◽  
Perianal Fistulas ◽  
Median Serum ◽  
Fistula Healing

Abstract Background Tumour necrosis factor (TNF) inhibitors are potent drugs effective for the treatment of both luminal disease and perianal fistulas in Crohn’s disease (CD). Recently, there is some evidence that patients with perianal disease might need higher concentrations of anti-TNF levels compared with patients without perianal disease. The aim of this study was to compare anti-TNF serum concentrations: IFX (infliximab) or ADA (adalimumab) between patients with active and closed perianal fistulas with CD. Methods Retrospective study including that was on anti-TNF for at least 6 months. Fistula closure was defined as absence of active drainage at gentle finger compression and/or fistula healing on magnetic resonance imaging/ultrasound. Results We included 55 patients with CD and perianal disease, 54.5% males, median age of 31 (interquartile range: 18–71) years. Forty-two were on IFX and 13 on ADA. Median IFX serum concentrations [IQR] were higher in patients with closed fistulas (n = 19) compared with patients with actively draining fistulas (n = 23): 7.7 mg/ml [0–32.6] vs. 1.5 mg/ml [0–9.5], respectively (p < 0.001). A similar difference was seen in patients treated with ADA: median serum concentrations were 9.6 mg/ml [6–21.9] in 10 patients with closed fistulas vs. 4 mg/ml [4–4.3] in 3 patients with producing fistulas, p = 0.007. Serum concentrations superior or equal to 4.68 mg/ml for IFX (AUC of 0.87; 95% CI: 0.73–0.96) were associated with fistula closure. Conclusion Higher serum levels of anti-TNF drugs were associated with perianal fistula closure. Patients with CD and perianal disease may benefit from intensification of biological therapy.

scholarly journals Higher anti-TNF serum levels are associated with perianal fistula closure in Crohn’s disease patients

2019 ◽  
Vol 54 (4) ◽  
pp. 453-458 ◽  
Author(s):  
Anne S. Strik ◽  
Mark Löwenberg ◽  
Christianne J. Buskens ◽  
Krisztina B. Gecse ◽  
Cyriel I. Ponsioen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Perianal Fistula ◽  
Serum Levels ◽  
Fistula Closure

scholarly journals P345 Lack of anti-TNF drugs levels in fistula tissue: A reason for non-response in Crohn’s perianal fistula?

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S330-S331
Author(s):  
S Adegbola ◽  
M Sarafian ◽  
K Sahnan ◽  
A Pechlivanis ◽  
R Phillips ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Limit Of Detection ◽  
Significant Proportion ◽  
Perianal Fistula ◽  
Serum Levels ◽  
Positive Control ◽  
Response To Therapy ◽  
Perianal Fistulas ◽  
Number Of Patients

Abstract Background Anti-TNF therapy is recommended as a treatment for patients with Crohn ́s perianal fistulas. However, a significant proportion of patients have a sub-optimal response to anti-TNF therapy. Higher serum levels of anti-TNF agents have been associated with improved outcomes in perianal Crohn’s disease. Currently, it is unknown whether anti-TNF agent levels can be detected in tissue from fistula tracts themselves and whether this is associated with response. Methods We undertook a pilot study to develop a method to measure fistula tissue levels of anti-TNF medication (infliximab and adalimumab) using a targeted proteomic technique that employs ‘signature peptide detection’ following trypsin digestion called ultraperformance liquid chromatography–mass spectrometry (UPLC-MS), to quantify a protein. The targeted UPLC- MS/MS detection and quantification method implemented were previously validated. Biopsies were obtained from patients with Crohn’s disease who underwent an examination under anaesthesia for worsening fistula symptoms despite maintenance anti-TNF therapy. Idiopathic (cryptoglandular) tissues from purposively sampled matched (age/gender) patients were analysed as negative controls and these samples were spiked with anti-TNF drugs as positive controls. Results Tissue was sampled from the fistula tracts of seven patients with Crohn’s perianal disease (5 patients were on adalimumab and 2 patients were on infliximab). The limit of detection (LOD) and linearity range of the method was assessed for each drug in the spiked idiopathic fistula samples. Infliximab and adalimumab had a LOD of 0.004 and 2 μg/ml respectively with linearity demonstrated for both drugs. The anti-TNF drugs, infliximab and adalimumab, were not detected in fistula samples from any of the Crohn’s patients despite detection in ‘spiked’ positive control samples. In addition, to validate the result, samples were concentrated (x10) and still there was no detection of the drugs in the test samples. Conclusion The anti-TNF drugs adalimumab and infliximab were not detected in fistula biopsy samples from patients with Crohn ́s perianal fistulas with refractory symptoms despite maintenance therapy. This raises the question on the role of tissue penetrance of anti-TNF drugs in response to therapy. Further work is required in a larger number of patients to validate the findings observed and investigate whether any correlation exists between tissue and serum levels of anti-TNF and clinical outcome.

scholarly journals OP005 Higher anti-TNF serum levels are associated with perianal fistula closure in Crohn’s disease patients

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S004-S004
Author(s):  
A Strik ◽  
M Löwenberg ◽  
C Ponsioen ◽  
K Gecse ◽  
C Buskens ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Perianal Fistula ◽  
Serum Levels ◽  
Fistula Closure

scholarly journals P586 Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S490-S491
Author(s):  
B GU ◽  
K Venkatesh ◽  
A J Williams ◽  
W Ng ◽  
C Corte ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Perianal Fistula ◽  
Secondary Outcome ◽  
Fistula Closure ◽  
Roc Curve Analysis ◽  
Perianal Crohn’S Disease ◽  
Fistula Healing ◽  
Trough Levels ◽  
Perianal Crohn's Disease

Abstract Background Anti-TNF α agents, including infliximab (IFX) and adalimumab (ADA), are arguably the most effective medical therapies for fistulising perianal Crohn’s disease (CD). Increased rates of perianal fistula healing have been reported with increased IFX trough levels. Our study aimed to determine the correlation between perianal fistula healing and closure with IFX and ADA trough levels in fistulising perianal CD patients on maintenance therapy. Methods In this multi-centre retrospective cross-sectional study, we identified CD patients with perianal fistulae on maintenance IFX or ADA who had an IFX or ADA trough level within 3 months of clinical assessment. Data collected included demographics, serum IFX and ADA trough levels (mg/l) and concomitant medical and surgical therapy. The primary outcome was fistula healing, defined as a cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing as well as closure of all external fistula openings. Receiver operating characteristic (ROC) curve analysis was performed to identify the IFX and ADA concentration cut-off points with combined maximal sensitivity and specificity that corresponded to fistula healing. Results A total of 123 patients (IFX = 72; ADA = 51) were included. Fifty-four (75.0%) patients on maintenance IFX achieved fistula healing and 22 (30.6%) achieved fistula closure. Patients who achieved fistula healing had significantly higher median IFX trough levels compared with patients who did not [6.2 (interquartile range 3.1 - 9.6) vs. 3.0 (0.3 - 6.2), (p = 0.007)]. The median IFX trough levels for patients with and without fistula closure were not significantly different [6.4 (2.9 - 9.8) vs. 4.9 (2.5 - 8.9), (p = 0.277)]. Forty (78.4%) patients on maintenance ADA achieved fistula healing and eighteen (35.3%) fistula closure. Patients who achieved fistula healing had a significantly higher median ADA level compared with those who did not [8.7 (6.6 - 12.0) vs. 5.4 (2.5 - 8.3), p = 0.007]. The median ADA trough levels for patients with fistula closure and without fistula closure were not significantly different [9.6 (6.7 – 12.0) vs. 7.7 (4.4–9.8), p = 0.098]. An IFX cut off point of 6.10mg/l was associated with healing (sensitivity 52%; specificity 78%; area under the curve (AUC) 0.72). An ADA cut off point of 7.05mg/l was associated with healing (sensitivity 70%; specificity 73%; AUC 0.77). Conclusion Higher IFX and ADA trough levels are associated with fistula healing. No association between IFX and ADA trough levels and fistula closure was seen, although larger numbers may be required. To the best our knowledge, this is the first study to demonstrate a significant association with both higher IFX and ADA levels with fistula healing in perianal CD.

scholarly journals Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn's disease

2017 ◽  
Vol 45 (7) ◽  
pp. 933-940 ◽  
Author(s):  
A. J. Yarur ◽  
V. Kanagala ◽  
D. J. Stein ◽  
F. Czul ◽  
M. A. Quintero ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Perianal Fistula ◽  
Fistula Healing ◽  
Trough Levels

scholarly journals Tu1724 – Association of Ustekinumab Serum Concentrations and Perianal Fistula Resolution in the Crohn's Disease Uniti Program

2019 ◽  
Vol 156 (6) ◽  
pp. S-1099-S-1100 ◽  
Author(s):  
Bruce E. Sands ◽  
Brian C. Kramer ◽  
Christopher Gasink ◽  
Douglas Jacobstein ◽  
Long-Long Gao ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Perianal Fistula ◽  
Serum Concentrations

scholarly journals Ambulatory Surgery for Perianal Crohn’s Disease: Study of Feasibility

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
S. Sibio ◽  
A. Di Giorgio ◽  
M. Campanelli ◽  
S. Di Carlo ◽  
A. Divizia ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Anal Canal ◽  
Outpatient Treatment ◽  
Perianal Disease ◽  
Fistula Tract ◽  
Clinical Issue ◽  
Perianal Fistulas ◽  
Referral Center ◽  
Distal Rectum

Background. One-third of Crohn’s disease (CD) patients present perianal fistula. The gold standard in the diagnosis and treatment of symptomatic perianal disease (PAD) in CD is the exploration of the anal canal and distal rectum under anesthesia (EUA). This procedure is mainly conducted as a day case surgery. Unfortunately, it is not always possible to proceed within the ideal timing and any delay may well represent a relevant clinical issue. The aim of this study was to evaluate the feasibility of outpatient treatment of symptomatic perianal fistulas in CD patients. Methods. All CD patients under regular follow-up at our inflammatory bowel disease referral center, presenting with symptomatic perianal fistulas, were offered surgical consultation. The data of patients were prospectively collected for three years (February 2014 to February 2017) for the purpose of the study. All clinical information, including previous EUA and/or records from MRI and endoscopic ultrasound, was included. Outpatient anal canal and distal rectum exploration and treatment (OE) were undertaken during the specialist surgical consultation. Fistulas were classified according to Parks’s classification; the type of outpatient treatment and compliance of patients were recorded. Pain was assessed by VAS at the time of the procedure and during the first control. Patients were followed up in the surgical clinic in relation to the study. Results. Ninety-two CD patients with symptomatic perianal fistulas had surgical consultation during the study period. OE was offered to all but 18 patients who fulfilled the exclusion criteria or had an extremely severe disease; six patients refused the OE (8.11%). Of the 68 patients undergoing OE, eleven (16.18%) had previous surgery for perianal disease. The OE was accomplished in sixty-one patients (89.71%), while in 7 patients, it was abandoned for scarce compliance. Nine patients (14.75%) underwent drainage of perianal abscess; in 3 of them, it was possible to probe the fistula tract, find the internal orifice, and pass a loose seton. Overall, setonage was performed in 50 patients (81.97%). Rectovaginal setons were placed in 3 patients and more than one seton (up to 3) in 6 cases. Fistulotomy was performed in 4 simple subcutaneous fistulous tracts. Concordance with the preoperative findings was found in 54 out of 61 patients. EUA was scheduled at the time of OE for the 7 patients who did not complete the procedure. All sixty-one patients who had the OE were followed up for a minimum of 12 months. Conclusions. This preliminary study indicates that OE in CD patients with symptomatic perianal fistulas is safe and feasible in a high-volume referral center. It might provide several benefits, including patients’ logistics, reduce or remove patients’ symptoms and discomfort, allow for a timely start of medical therapy, and avoid further complications.

scholarly journals Serum levels of NLRC4 and MCP-2/CCL8 in patients with active Crohn’s disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260034
Author(s):  
Kader Irak ◽  
Mehmet Bayram ◽  
Sami Cifci ◽  
Gulsen Sener
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intestinal Epithelial ◽  
Intestinal Homeostasis ◽  
Median Serum ◽  
Circulating Levels

Crohn’s disease (CD) is characterized by malfunction of immune-regulatory mechanisms with disturbed intestinal mucosal homeostasis and increased activation of mucosal immune cells, leading to abnormal secretion of numerous pro- and anti-inflammatory mediators. MCP2/CCL8 is produced by intestinal epithelial cells and macrophages, and is a critical regulator of mucosal inflammation. NLRC4 is expressed in phagocytes and intestinal epithelial cells and is involved in intestinal homeostasis and host defense. However, no study to date has assessed the circulating levels of NLRC4 and MCP2/CCL8 in patients with CD. The study was aimed to investigate the serum levels of MCP2/CCL8 and NLRC4 in patients with active CD. Sixty-nine patients with active CD and 60 healthy participants were included in the study. Serum levels of NLRC4 and MCP2/CCL8 were determined using an enzyme-linked immunosorbent assay. The median serum NLRC4 levels were lower in the patient group than in the controls (71.02 (range, 46.59–85.51) pg/mL vs. 99.43 (range 83.52–137.79) pg/mL) (P < 0.001). The median serum levels of MCP2/CCL8 were decreased in patients with CD (28.68 (range, 20.16–46.0) pg/mL) compared with the controls (59.96 (range, 40.22–105.59) pg/mL) (P < 0.001). Cut-off points of NLRC4 (<81 pg/mL) and MCP2/CCL8 (<40 pg/mL) showed high sensitivity and specificity for identifying active CD. In conclusion, this is the first study to examine circulating levels of MCP2/CCL8 and NLRC4 in patients with active CD. Our results suggest that serum NLRC4 and MCP2/CCL8 levels may be involved in the pathogenesis of CD and may have a protective effect on intestinal homeostasis and inflammation. Serum levels of MCP2/CCL8 and NLRC4 could be used as a diagnostic tool and therapeutic target for CD.

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