Fecal Calprotectin Pretreatment and Induction Infliximab Levels for Prediction of Primary Nonresponse to Infliximab Therapy in Crohn’s Disease

2018 ◽  
Vol 37 (2) ◽  
pp. 108-115 ◽  
Author(s):  
Belén Beltrán ◽  
Marisa Iborra ◽  
Esteban Sáez-González ◽  
Maria R. Marqués-Miñana ◽  
Inés Moret ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inverse Correlation ◽  
Drug Level ◽  
Fecal Calprotectin ◽  
Primary Response ◽  
Induction Treatment ◽  
Inflammatory Parameters ◽  
Inflammatory Bowel ◽  
Monitoring And Measurement

Introduction: The association between infliximab (IFX) and fecal calprotectin (FC) levels on one hand, and the clinical and endoscopic response of patients with inflammatory bowel disease on the other, is well established. Objective and Methods: To investigate the association between inflammatory biochemical parameters and serum concentrations of IFX during induction treatment with a primary nonresponse in a prospective cohort of Crohn’s disease (CD) patients. Results: Of the 35 patients included, 8 (22.8%) had primary nonresponse at the end of induction. Induction IFX levels were lower among primary nonresponders at weeks 6 and 14 (week 6: median IFX level 7.3 vs. 11.2 μg/mL, respectively, p = 0.090; week 14: median IFX level 1.5 vs. 4.7 μg/mL, respectively, p = 0.020). FC levels were higher in patients with primary nonresponse versus primary response at weeks 0, 6, and 14 (week 0: median FC level 1,830 vs. 410 μg/g, ­respectively, p = 0.030; week 6: median FC level 1,150 vs. 230 μg/g, respectively, p = 0.074; week 14: median FC level 1,210 vs. 208 μg/g, respectively, p = 0.060). For the multivariate analysis, the median IFX level at week 14 and median FC level at week 0 were independently associated with primary nonresponse. A significant inverse correlation was determined between FC level at week 0 and IFX level at week 14 (Spearman’s rho correlation, 0.440; p < 0.05). Conclusions: IFX levels (at week 14) and baseline FC levels could predict primary nonresponse after induction IFX therapy in patients with CD. A high baseline inflammatory load might modify the pharmacokinetic processes of anti-tumor necrosis factor drugs. Drug level monitoring and measurement of baseline inflammatory parameters could improve the efficacy of IFX in the induction therapy of patients with active CD.

scholarly journals P576 Ustekinumab levels correlate with induction fecal calprotectin drop-slope and discriminate the need for intensification at week 52 in Crohn’s Disease patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S533-S534
Author(s):  
B Mateos ◽  
E Sáez-González ◽  
M Iborra ◽  
I Moret ◽  
A Cañada ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Biological Markers ◽  
Pearson Correlation ◽  
Extended Period ◽  
Fecal Calprotectin ◽  
Induction Treatment ◽  
Drug Levels ◽  
Inflammatory Parameters ◽  
Tnf Α

Abstract Background Ustekinumab (UST) intensification during Crohn’s Disease (CD) treatment is becoming common in clinical practice. Little is known about early intensification maintenance regimens and their drug levels utility in discriminating CD-response and the need for further intensification. We aim to analyze UST levels’ evolution in an intensified maintenance regimen, their capacity to discriminate response according to inflammatory parameters and indicate the need for further intensification. Methods This is a retrospective study with 43 moderate/severe active CD patients (Harvey-Bradshaw Index [HBI] ≥4 and Fecal Calprotectin [FC] &gt;250 µg/g) who received UST induction treatment (induction dose of 6mg/kg IV, plus dose of 90mg SC at week 8). Patients received maintenance treatment (90mg SC/8 weeks) and were followed for 52 weeks. They were classified according to the response obtained at the first year in responders (R), HBI &lt;3 and FC &lt;200µg/g; non-responders (NR), HBI ≥4 and FC &gt;250µg/g; and intensification group (IG), partially responders that needed UST intensification to every 4 weeks. HBI, FC, C-Reactive Protein (CRP), and UST levels data were collected at baseline (w0), week 8 (w8), week 16 (w16), and 52 weeks (w52) of maintenance. IG was followed 12–26 weeks after intensification (aI). Results Half of the patients (48.8%) were male. Most of them (97.7%) have received previous anti-TNF-α treatment (53.49% ≥2 anti-TNF-α). Patients’ median age at the moment of starting UST was 51 (37.5, 58.5) years. Median disease duration was 11 (7.5, 23) years. Location of disease was ileal in 30% of patients and ileocolic in 53%. One-third of patients suffered perianal disease, and 41 % were smokers. The only demographic factor associated with non-response was ileocolic location. Table 1 shows the evolution of inflammatory parameters and UST levels according to the response. A Pearson correlation (r=0.62) between higher FC drop (baseline-w16) and higher drug levels at w16 was observed. The evolution of biological markers discriminates NR during induction; however, neither biological markers nor UST level can distinguish between R and those who will need intensification. R shows higher UST levels at w52 compared to IG. IG showed a significant increase of UST levels (mean of 5.39 points) and a substantial drop of FC and HBI (mean of 115.62 and 2.27 points, respectively) after intensification. Those patients reported clinical improvement; however, they could not reach a FC &lt;250µg/g, which could need a more extended period to decrease. Conclusion FC drop-slope is associated with higher levels of UST at the end of induction. UST levels at w52 are useful for discriminating patients who will benefit from UST intensification every 4 weeks.

scholarly journals Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

2021 ◽  
Author(s):  
Shinichiro Shinzaki ◽  
Katsuyoshi Matsuoka ◽  
Hiroki Tanaka ◽  
Fuminao Takeshima ◽  
Shingo Kato ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Fecal Calprotectin ◽  
Potential Biomarker ◽  
Adalimumab Therapy ◽  
Adalimumab Treatment ◽  
Inflammatory Bowel

Abstract Background This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

scholarly journals FECAL CALPROTECTIN: levels for the ethiological diagnosis in Brazilian patients with gastrointestinal symptoms

2015 ◽  
Vol 52 (1) ◽  
pp. 50-54 ◽  
Author(s):  
Lorete Maria da Silva KOTZE ◽  
Renato Mitsunori NISIHARA ◽  
Sandra Beatriz MARION ◽  
Murilo Franco CAVASSANI ◽  
Paulo Gustavo KOTZE
Keyword(s):  
Ulcerative Colitis ◽  
Irritable Bowel Syndrome ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Bowel Diseases ◽  
Fecal Calprotectin ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Irritable Bowel ◽  
Active Disease

Background Determination of fecal calprotectin can provide an important guidance for the physician, also in primary care, in the differential diagnosis of gastrointestinal disorders, meanly between inflammatory bowel diseases and irritable bowel syndrome. Objectives The aims of the present study were to prospectively investigate, in Brazilian adults with gastrointestinal complaints, the value of fecal calprotectin as a biomarker for the differential diagnosis between functional and organic disorders and to correlate the concentrations with the activity of inflammatory bowel diseases. Methods The study included consecutive patients who had gastrointestinal complaints in which the measurement levels of fecal calprotectin were recommended. Fecal calprotectin was measured using a Bühlmann (Basel, Switzerland) ELISA kit Results A total of 279 patients were included in the study, with median age of 39 years (range, 18 to 78 years). After clinical and laboratorial evaluation and considering the final diagnosis, patients were allocated into the following groups: a) Irritable Bowel Syndrome: 154 patients (102 female and 52 male subjects). b) Inflammatory Bowel Diseases group: 112 patients; 73 with Crohn’s disease; 38 female and 35 male patients; 52.1% (38/73) presented active disease, and 47.9% (35/73) had disease in remission and 39 patients with ulcerative colitis;19 female and 20 male patients; 48.7% (19/39) classified with active disease and 49.3% (20/39) with disease in remission. A significant difference (P<0.001) was observed between the median value of fecal calprotectin in Irritable Bowel Syndrome group that was 50.5 µg/g (IQR=16 - 294 µg/g); 405 µg/g (IQR=29 - 1980 µg/g) in Crohn’s disease patients and 457 µg/g (IQR=25 - 1430 µg/g) in ulcerative colitis patients. No difference was observed between the values found in the patients with Crohn’s disease and ulcerative colitis. Levels of fecal calprotectin were significantly lower in patients with inflammatory bowel diseases in remission when compared with active disease (P<0.001). Conclusions The present study showed that the determination of fecal calprotectin assists to differentiate between active and inactive inflammatory bowel diseases and between inflammatory bowel diseases and irritable bowel syndrome.

scholarly journals Validation of Neutrophil CD64 Blood Biomarkers to Detect Mucosal Inflammation in Pediatric Crohn’s Disease

2017 ◽  
Vol 24 (1) ◽  
pp. 198-208 ◽  
Author(s):  
Phillip Minar ◽  
Kimberly Jackson ◽  
Yi-Ting Tsai ◽  
Heidi Sucharew ◽  
Michael J Rosen ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Surface Expression ◽  
Fecal Calprotectin ◽  
Mucosal Inflammation ◽  
Neutrophil Cd64 ◽  
Severity Scores ◽  
Inflammatory Bowel

Abstract Background In a pilot study, neutrophil CD64 surface expression was significantly elevated in newly diagnosed, pediatric-onset Crohn’s disease. We aimed to test the CD64 biomarkers (neutrophil CD64 surface expression and soluble CD64) as determinates for mucosal inflammation in a larger pediatric Crohn’s cohort with the hypotheses that the CD64 biomarkers would reliably detect intestinal inflammation and correlate with endoscopic severity scores. Methods We enrolled patients referred for colonoscopy for either suspected inflammatory bowel disease or with established Crohn’s. Neutrophil CD64 index was determined by flow cytometry using a commercial kit (Leuko64, Trillium) and soluble CD64 by ELISA (LifeSpan). Results A total of 209 patients (72 controls, 76 new inflammatory bowel disease patients, and 61 established Crohn’s) were enrolled. Both neutrophil CD64 index and soluble CD64 were significantly elevated in new Crohn’s compared with controls. The area under the curve (AUC) for neutrophil CD64 index ≥1 was 0.85 (95% confidence interval, 0.77–0.92), 75% sensitive and 89% specific for new Crohn’s. Comparatively, soluble CD64 ≥39 ng/mL was 92% sensitive and 85% specific (AUC, 0.93) for new Crohn’s. Neutrophil CD64 index, soluble CD64, and fecal calprotectin discriminated endoscopic inactive from moderate and severe activity while soluble CD64 differentiated endoscopic mild from moderate and severe activity. Neutrophil CD64 index (r = 0.46, P &lt; 0.001) and fecal calprotectin (r = 0.55, P &lt; 0.001) correlated well with the Simple Endoscopic Score–Crohn’s disease. Spearman correlation between the CD64 index and calprotectin was 0.39 (P &lt; 0.001). Conclusions In a large Crohn’s disease cohort, we found that neutrophil CD64 index and soluble CD64 were significantly elevated during active gastrointestinal inflammation. 10.1093/ibd/izx022_video1 izx022.video1 5732761255001

scholarly journals PARADOXICAL CROHN’S DISEASE – MYTH OR REALITY?

2017 ◽  
Vol 26 (1) ◽  
pp. 45-49
Author(s):  
Cristina Pomirleanu ◽  
◽  
Catalina Mihai ◽  
Codrina Ancuta ◽  
◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Fecal Calprotectin ◽  
Positive Outcomes ◽  
Drug Induced ◽  
Immune Mediated ◽  
Histopathologic Evaluation ◽  
Inflammatory Bowel ◽  
Optimal Treatment Strategy ◽  
New Onset

We report the clinical case of an emergent Crohn’s disease (CD) as a paradoxical effect after 24 months of successfully treatment with etanercept for active ankylosing spondylitis in a young women. Despite rapid and sustained response of articular disease (remission achieved as soon as three months and maintained through the entire period of administration), new onset intestinal manifestations developed during biological therapy. A complex assessment comprising clinical, endoscopic and histopathologic evaluation, associated with high levels of fecal calprotectin confirmed drug-induced inflammatory bowel disease (IBD) compatible with CD. Although optimal treatment strategy is not yet validated, discontinuation of putative etanercept and cycling to a monoclonal anti-TNF antibody (adalimumab) demonstrated positive outcomes for both articular and IBD. New onset CD may be considered as an immune-mediated injury induced etanercept and should be considered in any patient with spondylarthritis in whom IBD develops with a clear temporal relationship with TNF inhibitors, especially etanercept.

scholarly journals Mucosal Healing in Crohn’s Disease: Bull’s Eye or Bust? The “Relative” Con Position

2021 ◽  
pp. 1-8
Author(s):  
Mahmoud Mosli ◽  
Turki Alameel ◽  
Ala I. Sharara
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Treatment Plan ◽  
Immunosuppressive Treatment ◽  
Fecal Calprotectin ◽  
Mucosal Healing ◽  
Inflammatory Bowel ◽  
Noninvasive Markers ◽  
Endoscopic Assessment ◽  
Bull's Eye

<b><i>Background:</i></b> Crohn’s disease is a progressive inflammatory bowel disease. Persistent untreated inflammation can cumulatively result in bowel damage in the form of strictures, fistulas, and fibrosis, which can ultimately result in the need for major abdominal surgery. Mucosal healing has emerged as an attractive, yet ambitious goal in the hope of preventing long-term complications. <b><i>Summary:</i></b> Clinical remission is an inadequate measure of disease activity. Noninvasive markers such as fecal calprotectin, CRP, or small bowel ultrasound are useful adjunct tools. However, endoscopic assessment remains the cornerstone in building a treatment plan. Achieving complete mucosal healing has proved to be an elusive goal even in the ideal setting of a clinical trial. <b><i>Key Messages:</i></b> Aiming for complete mucosal healing in all patients may result in overuse of medications, higher costs, and potential side effects of aggressive immunosuppressive treatment. More practical goals such as relative or partial healing, for example, 50% improvement in inflammation and reduction in size of ulcers, ought to be considered, particularly in difficult-to-treat populations.

scholarly journals Early infliximab antibody testing does not prevent infusion reactions when reinitiating infliximab

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Joseph D. Feuerstein
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Antibody Formation ◽  
Potential Benefit ◽  
Drug Level ◽  
Additional Benefit ◽  
Antibody Testing ◽  
Infusion Reactions ◽  
Inflammatory Bowel

Infliximab drug level checking has started to revolutionize the treatment of inflammatory bowel disease, allowing for more accurate dosing. Recently, Brandse and colleagues and Gagniere and colleagues both noted the potential benefit of a re-introduction of infliximab after prior failure in patients with Crohn’s disease. Unfortunately though, approximately 1/3 of patients stopped the drug due to side effects of the attempted retreatment from infusion reactions. In their study, they also noted that concomitant usage of a thiopurine did not provide any additional benefit. Presumably, majority of these reactions are secondary to antibody formation to infliximab. In order to reduce the risk of infusion reactions, we present a case of a patient with Crohn’s disease who was retried on infliximab and had antibody testing after the first dose to assess if it would be safe to continue the drug, as most infusion reactions occur at the second dose.

scholarly journals Calprotectin Is a Useful Tool in Distinguishing Coexisting Irritable Bowel-Like Symptoms from That of Occult Inflammation among Inflammatory Bowel Disease Patients in Remission

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Lars-Petter Jelsness-Jørgensen ◽  
Tomm Bernklev ◽  
Bjørn Moum
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Fecal Calprotectin ◽  
Elisa Test ◽  
Rome Ii Criteria ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Irritable Bowel

Background and Aim. In the inflammatory bowel diseases (IBDs), many symptoms are similar to the functional disorder irritable bowel syndrome (IBS). A challenge is thus to distinguish symptoms of IBD from IBS. The aim of this study was to investigate the levels of calprotectin in IBS-positive IBD patients in remission.Methods. Remission was defined as a simple clinical colitis activity index (SCCAI) or simple crohn’s disease activity index (SCDAI) score of less than three and less than four, respectively. The Rome II criteria were used to identify cases, and the calprotectin ELISA test was used to quantify calprotectin in stools.Results. The Rome II criteria were fulfilled in 24.6% of ulcerative colitis (UC) patients, while the comparable number for Crohn's disease (CD) was 21.4%. There was a tendency for elevated fecal calprotectin levels in IBS-positive patients, regardless of diagnosis. However, these differences were only significant in CD.Conclusions. Calprotectin levels are elevated in subgroups of IBD patients that are in remission and have coexisting IBS-like symptoms. This study underscores the clinical usefulness of a noninvasive marker to distinguish patients in need of intensified followup from those that do not need further workup.

scholarly journals Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease

2018 ◽  
Vol 11 ◽  
pp. 175628481875993 ◽  
Author(s):  
Arne Carlsen ◽  
Roald Omdal ◽  
Kristian Øgreid Leitao ◽  
Kjetil Isaksen ◽  
Anne Kristine Hetta ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Fecal Calprotectin ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Inflammatory Bowel

Background: Low anti-tumor necrosis factor α (TNFα) serum concentrations may result in lack of treatment response in patients with inflammatory bowel disease. We determined the anti-TNFα 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-TNFα agents. These findings were not observed in patients with ulcerative colitis. Clinicaltrials.gov identifier [NCT02134054]

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