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]

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.

Validation of the “German Inflammatory Bowel Disease Activity Index (GIBDI)”: An Instrument for Patient-Based Disease Activity Assessment in Crohn’s Disease and Ulcerative Colitis

2018 ◽  
Vol 56 (10) ◽  
pp. 1267-1275 ◽  
Author(s):  
Angelika Hüppe ◽  
Jana Langbrandtner ◽  
Winfried Häuser ◽  
Heiner Raspe ◽  
Bernd Bokemeyer
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Inflammatory Bowel ◽  
Activity Indices

Abstract Introduction Assessment of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC) is usually based on the physician’s evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians’ documented activity indices. Methods Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. Results Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). Discussion There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.

scholarly journals The association between inflammatory potential of diet and disease activity: results from a cross-sectional study in patients with inflammatory bowel disease

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Carlijn R. Lamers ◽  
Nicole M. de Roos ◽  
Ben J. M. Witteman
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Activity Index ◽  
Statistical Significance ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Abstract Background Diet may play a role in disease status in patients with inflammatory bowel disease. We tested whether the inflammatory potential of diet, based on a summation of pro- and anti-inflammatory nutrients, is associated with disease activity in patients with Crohn’s disease and ulcerative colitis. Methods Participants completed a disease activity questionnaire (short Crohn’s Disease Activity (sCDAI) or Patient Simple Clinical Colitis Activity Index (P-SCCAI)) and a Food Frequency Questionnaire (FFQ). FFQ data were used to calculate the Dietary Inflammatory Index (DII) which enables categorization of individuals’ diets according to their inflammatory potential on a continuum from pro- to anti-inflammatory. Associations with disease activity were investigated by multiple linear regression. Results The analysis included 329 participants; 168 with Crohn’s disease (median sCDAI score 93 [IQR 47–156]), and 161 with ulcerative colitis (median P-SCCAI score 1 [IQR 1–3]). Mean DII was 0.71 ± 1.33, suggesting a slightly pro-inflammatory diet. In Crohn’s disease, the DII was positively associated with disease activity, even after adjustment for confounders (p = 0.008). The mean DII was significantly different between participants in remission and with mild and moderately active disease (0.64, 0.97 and 1.52 respectively, p = 0.027). In ulcerative colitis, the association was not significant. Conclusions Disease activity was higher in IBD participants with a more pro-inflammatory diet with statistical significance in Crohn’s disease. Although the direction of causality is not clear, this association strengthens the role for diet in medical treatment, which should be tested in an intervention study.

scholarly journals Intestinal Ultrasound in Inflammatory Bowel Disease: A Valuable and Increasingly Important Tool

2021 ◽  
pp. 1-17
Author(s):  
Catarina Frias-Gomes ◽  
Joana Torres ◽  
Carolina Palmela
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Response To Therapy ◽  
Inflammatory Bowel

<b><i>Background:</i></b> Intestinal ultrasound is emerging as a non-invasive tool for monitoring disease activity in inflammatory bowel disease patients due to its low cost, excellent safety profile, and availability. Herein, we comprehensively review the role of intestinal ultrasound in the management of these patients. <b><i>Summary:</i></b> Intestinal ultrasound has a good accuracy in the diagnosis of Crohn’s disease, as well as in the assessment of disease activity, extent, and evaluating disease-related complications, namely strictures, fistulae, and abscesses. Even though not fully validated, several scores have been developed to assess disease activity using ultrasound. Importantly, intestinal ultrasound can also be used to assess response to treatment. Changes in ultrasonographic parameters are observed as early as 4 weeks after treatment initiation and persist during short- and long-term follow-up. Additionally, Crohn’s disease patients with no ultrasound improvement seem to be at a higher risk of therapy intensification, need for steroids, hospitalisation, or even surgery. Similarly to Crohn’s disease, intestinal ultrasound has a good performance in the diagnosis, activity, and disease extent assessment in ulcerative colitis patients. In fact, in patients with severe acute colitis, higher bowel wall thickness at admission is associated with the need for salvage therapy and the absence of a significant decrease in this parameter may predict the need for colectomy. Short-term data also evidence the role of intestinal ultrasound in evaluating therapy response, with ultrasound changes observed after 2 weeks of treatment and significant improvement after 12 weeks of follow-up in ulcerative colitis. <b><i>Key Messages:</i></b> Intestinal ultrasound is a valuable tool to assess disease activity and complications, and to monitor response to therapy. Even though longer prospective data are warranted, intestinal ultrasound may lead to a change in the paradigm of inflammatory bowel disease management as it can be used in a point-of-care setting, enabling earlier intervention if needed.

scholarly journals Anemia in inflammatory bowel disease: prevalence, differential diagnosis and association with clinical and laboratory variables

2014 ◽  
Vol 132 (3) ◽  
pp. 140-146 ◽  
Author(s):  
Rodrigo Andrade Alves ◽  
Sender Jankiel Miszputen ◽  
Maria Stella Figueiredo
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Iron Deficiency ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Activity Index ◽  
Deficiency Anemia ◽  
Inflammatory Bowel

CONTEXT AND OBJECTIVES:Anemia is the most frequent extraintestinal complication of inflammatory bowel disease. This study aimed to: 1) determine the prevalence of anemia among patients with inflammatory bowel disease; 2) investigate whether routine laboratory markers are useful for diagnosing anemia; and 3) evaluate whether any association exists between anemia and clinical/laboratory variables.DESIGN AND SETTING:Cross-sectional at a federal university.METHODS:44 outpatients with Crohn's disease and 55 with ulcerative colitis were evaluated. Clinical variables (disease activity index, location of disease and pharmacological treatment) and laboratory variables (blood count, iron laboratory, vitamin B12 and folic acid) were investigated.RESULTS:Anemia and/or iron laboratory disorders were present in 75% of the patients with Crohn's disease and in 78.2% with ulcerative colitis. Anemia was observed in 20.5% of the patients with Crohn's disease and in 23.6% with ulcerative colitis. Iron-deficiency anemia was highly prevalent in patients with Crohn's disease (69.6%) and ulcerative colitis (76.7%). Anemia of chronic disease in combination with iron deficiency anemia was present in 3% of the patients with Crohn's disease and in 7% of the patients with ulcerative colitis. There was no association between anemia and disease location. In ulcerative colitis, anemia was associated with the disease activity index.CONCLUSIONS:Most patients present iron laboratory disorders, with or without anemia, mainly due to iron deficiency. The differential diagnosis between the two most prevalent types of anemia was made based on clinical data and routine laboratory tests. In ulcerative colitis, anemia was associated with the disease activity index.

scholarly journals Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn’s disease

2020 ◽  
pp. 205064062097737
Author(s):  
T Manon-Jensen ◽  
S Sun ◽  
M Lindholm ◽  
V Domislović ◽  
P Giuffrida ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Surrogate Marker ◽  
Area Under The Curve ◽  
Inflammatory Bowel ◽  
Active Disease

Background Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn’s disease and ulcerative colitis. Methods We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulfate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn’s disease and 29 ulcerative colitis patients with active and inactive disease was included. Results In the acute and chronic dextran sulfate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn’s disease ( p < 0.05) and ulcerative colitis ( p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve: 0.81, p = 0.0009) and Crohn’s disease (area under the curve: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (Area under the curve: 0.75, p = 0.0219) and Crohn’s disease patients with active disease from those in remission (area under the curve: 0.68, p = 0.05). Conclusion PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn’s disease.

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