scholarly journals Clinical Relevance of Anti-TNF Antibody Trough Levels and Anti-Drug Antibodies in Treating Inflammatory Bowel Disease Patients

2020 ◽  
pp. 1-10
Author(s):  
Ilana Reinhold ◽  
Sena Blümel ◽  
Jens Schreiner ◽  
Onur Boyman ◽  
Jan Bögeholz ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Clinical Disease ◽  
Therapeutic Drug ◽  
Real World Data ◽  
Significant Treatment ◽  
Infusion Reactions ◽  
Inflammatory Bowel ◽  
Trough Levels

<b><i>Background and Aims:</i></b> The majority of patients treated with anti-tumor necrosis factor (TNF) therapy develop anti-drug antibodies (ADAs), which might result in loss of treatment efficacy. Strict guidelines on measuring trough levels (TLs) and ADA in clinical routine do not exist. To provide real-world data, we took advantage of our tertiary inflammatory bowel disease (IBD) center patient cohort and determined indicators for therapeutic drug monitoring (TDM) and actual consequences in patient care. <b><i>Methods:</i></b> We retrospectively collected clinical data of 104 IBD patients treated with infliximab or adalimumab in our IBD clinic. Patients with TL and ADA measurements between June 2015 and February 2018 were included. <b><i>Results:</i></b> The main reason for determining TL was increased clinical disease. Subtherapeutic TLs were found in 33 patients, therapeutic TLs in 33 patients, and supratherapeutic TLs in 38 patients. Adjustments in anti-TNF therapy occurred more frequently (<i>p</i> = 0.01) in patients with subtherapeutic TL (24 of 33 patients; 73%) as compared to patients with therapeutic and supratherapeutic TLs (26 of 71 patients; 37%). No correlation could be found between TL and disease activity (<i>p</i> = 0.16). Presence of ADA was found in 16 patients, correlated with the development of infusion reactions (OR: 10.6, RR: 5.4, CI: 2.9–38.6), and was associated with subtherapeutic TL in 15 patients (93.8%). Treatment adaptations were based on TL and/or ADA presence in 36 of 63 patients. <b><i>Conclusions:</i></b> TDM showed significant treatment adaptations in patients with subtherapeutic TL. Conversely, in patients with therapeutic and supratherapeutic TLs, reasons for adaptations were based on considerations other than TL, such as clinical disease activity. Further studies should focus on decision-making in patients presenting with supratherapeutic TL in remission.

scholarly journals Switching from originator infliximab to the biosimilar CT-P13 in 313 patients with inflammatory bowel disease

2018 ◽  
Vol 11 ◽  
pp. 175628481880124 ◽  
Author(s):  
Viktoria Bergqvist ◽  
Mohammad Kadivar ◽  
Daniel Molin ◽  
Leif Angelison ◽  
Per Hammarlund ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Disease Activity ◽  
Bowel Disease ◽  
Clinical Disease ◽  
Clinical Disease Activity ◽  
Inflammatory Bowel ◽  
Trough Levels

Background: As the patents of originator biologics are expiring, biosimilar versions are becoming available for the treatment of inflammatory bowel disease (IBD). However, published switch studies of the first infliximab biosimilar, CT-P13, have delivered ambiguous results that could be interpreted as showing a trend towards inferior effectiveness in Crohn’s disease (CD) compared with ulcerative colitis (UC). The aim of this study was to investigate the effectiveness and safety of switching IBD patients from treatment with Remicade to CT-P13. Methods: In this prospective observational cohort study, all adult IBD patients on Remicade treatment, at four hospitals, were switched to CT-P13. The primary endpoint was change in clinical disease activity at 2, 6, and 12 months after the switch. Secondary endpoints were subgroup analyses of patients with and without concomitant immunomodulators; changes in biomarkers, quality of life, drug trough levels and anti-drug antibodies (ADAbs); and adverse events. Results: A total of 313 IBD patients were switched (195 CD; 118 UC). There were no significant changes in clinical disease activity, quality of life, biomarkers (except a small but significant increase in albumin in CD) including F-calprotectin, drug trough levels, or proportion of patients in remission. Disease worsening rates were 14.0% for CD and 13.8% for UC; and 2.7% developed ADAbs and 2.2% developed serious adverse events. Conclusions: This is the largest study of switched IBD patients published to date, and it demonstrates that switching from Remicade to CT-P13 may be done with preserved therapeutic effectiveness and safety in both CD and UC.

scholarly journals Correlating Gastrointestinal Histopathologic Changes to Clinical Disease Activity in Dogs With Idiopathic Inflammatory Bowel Disease

2018 ◽  
Vol 56 (3) ◽  
pp. 435-443 ◽  
Author(s):  
Karin A. Allenspach ◽  
Jonathan P. Mochel ◽  
Yingzhou Du ◽  
Simon L. Priestnall ◽  
Frances Moore ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Scoring System ◽  
Activity Index ◽  
Clinical Disease ◽  
Clinical Activity ◽  
Clinical Disease Activity ◽  
Inflammatory Bowel ◽  
Histopathologic Changes

Prior studies have failed to detect a convincing association between histologic lesions of inflammation and clinical activity in dogs with inflammatory bowel disease (IBD). We hypothesized that use of a simplified histopathologic scoring system would improve the consistency of interpretation among pathologists when describing histologic lesions of gastrointestinal inflammation. Our aim was to evaluate the correlation of histopathologic changes to clinical activity in dogs with IBD using this new system. Forty-two dogs with IBD and 19 healthy control dogs were enrolled in this retrospective study. Endoscopic biopsies from the stomach, duodenum, ileum, and colon were independently scored by 8 pathologists. Clinical disease activity was scored using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) or the Canine Chronic Enteropathy Clinical Activity Index (CCECAI), depending on the individual study center. Summative histopathological scores and clinical activity were calculated for each tissue (stomach, duodenum, ileum, and colon) and each tissue histologic score (inflammatory/morphologic feature). The correlation between CCECAI/CIBDAI and summative histopathologic score was significant ( P < .05) for duodenum ( r = 0.42) and colon ( r = 0.33). In evaluating the relationship between histopathologic scores and clinical activity, significant ( P < .05) correlations were observed for crypt dilation ( r = 0.42), lamina propria (LP) lymphocytes ( r = 0.40), LP neutrophils ( r = 0.45), mucosal fibrosis ( r = 0.47), lacteal dilation ( r = 0.39), and villus stunting ( r = 0.43). Compared to earlier grading schemes, the simplified scoring system shows improved utility in correlating histopathologic features (both summative histology scores and select histologic scores) to IBD clinical activity.

scholarly journals Effect of Cognitive Behavioral Therapy on Clinical Disease Course in Adolescents and Young Adults With Inflammatory Bowel Disease and Subclinical Anxiety and/or Depression: Results of a Randomized Trial

2019 ◽  
Vol 25 (12) ◽  
pp. 1945-1956 ◽  
Author(s):  
Gertrude van den Brink ◽  
Luuk Stapersma ◽  
Anna Sophia Bom ◽  
Dimitris Rizopolous ◽  
C Janneke van der Woude ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cognitive Behavioral Therapy ◽  
Disease Activity ◽  
Bowel Disease ◽  
Behavioral Therapy ◽  
Fecal Calprotectin ◽  
Clinical Disease ◽  
Disease Course ◽  
First Relapse ◽  
Inflammatory Bowel

Abstract Background Anxiety and depressive symptoms are prevalent in patients with inflammatory bowel disease (IBD) and may negatively influence disease course. Disease activity could be affected positively by treatment of psychological symptoms. We investigated the effect of cognitive behavioral therapy (CBT) on clinical disease course in 10–25-year-old IBD patients experiencing subclinical anxiety and/or depression. Methods In this multicenter parallel group randomized controlled trial, IBD patients were randomized to disease-specific CBT in addition to standard medical care (CBT + care us usual [CAU]) or CAU only. The primary outcome was time to first relapse in the first 12 months. Secondary outcomes were clinical disease activity, fecal calprotectin, and C-reactive protein (CRP). Survival analyses and linear mixed models were performed to compare groups. Results Seventy patients were randomized (CBT+CAU = 37, CAU = 33), with a mean age of 18.3 years (±50% &lt; 18 y, 31.4% male, 51.4% Crohn’s disease, 93% in remission). Time to first relapse did not differ between patients in the CBT+CAU group vs the CAU group (n = 65, P = 0.915). Furthermore, clinical disease activity, fecal calprotectin, and CRP did not significantly change over time between/within both groups. Exploratory analyses in 10–18-year-old patients showed a 9% increase per month of fecal calprotectin and a 7% increase per month of serum CRP in the CAU group, which was not seen in the CAU+CBT group. Conclusions CBT did not influence time to relapse in young IBD patients with subclinical anxiety and/or depression. However, exploratory analyses may suggest a beneficial effect of CBT on inflammatory markers in children.

scholarly journals Distinct Cutoff Values of Adalimumab Trough Levels Are Associated With Different Therapeutic Outcomes in Patients With Inflammatory Bowel Disease

2019 ◽  
Vol 1 (3) ◽  
Author(s):  
Sang Hyoung Park ◽  
Badr Al-Bawardy ◽  
Satimai Aniwan ◽  
Sunanda V Kane ◽  
Nayantara Coelho-Prabhu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Cutoff Value ◽  
Reactive Protein ◽  
Therapeutic Outcomes ◽  
Inflammatory Bowel ◽  
Relationship Of ◽  
The Relationship ◽  
Trough Levels

Abstract Background and Aims We aimed to evaluate the relationship of serum adalimumab trough levels (ATL) with disease activity of inflammatory bowel disease (IBD) patients in a large, well-characterized referral center-based cohort. Methods We compared serum ATL between those with clinical, biochemical, or endoscopic/radiologic disease activity and those without. Results A total of 236 patients with IBD were included. Higher cutoff levels were associated with endoscopic and/or radiologic responses (cutoff value: 5.3 mcg/mL, P = 0.003) compared with improvement in C-reactive protein (cutoff value: 4.3 mcg/mL, P = 0.031). Conclusions Higher cutoff ATL was associated with endoscopic and/or radiologic response.

Su1345 Patterns of Antibiotic Exposure and Clinical Disease Activity in Inflammatory Bowel Disease: A 4 Year Prospective Study

2014 ◽  
Vol 146 (5) ◽  
pp. S-442
Author(s):  
Jana G. Hashash ◽  
Claudia M. Ramos Rivers ◽  
Miguel Regueiro ◽  
Arthur Barrie ◽  
Marc Schwartz ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Prospective Study ◽  
Disease Activity ◽  
Bowel Disease ◽  
Clinical Disease ◽  
Antibiotic Exposure ◽  
Clinical Disease Activity ◽  
Inflammatory Bowel

Su1255 Fecal Calprotectin Is Elevated With Clinical Disease Activity During Pregnancy in Women With Inflammatory Bowel Disease

2015 ◽  
Vol 148 (4) ◽  
pp. S-452 ◽  
Author(s):  
Vivian Huang ◽  
Jasmin Bal ◽  
Rae R. Foshaug ◽  
Lindsy Ambrosio ◽  
Karen Kroeker ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Fecal Calprotectin ◽  
Clinical Disease ◽  
Clinical Disease Activity ◽  
Inflammatory Bowel

scholarly journals P021 Circulating inflammatory protein and cellular profiles at time of diagnosis classify inflammatory bowel disease patients according to their underlying immune response and clinical disease course

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S139-S139
Author(s):  
M Heredia ◽  
M Charrout ◽  
R Klomberg ◽  
M Aardoom ◽  
M Jongsma ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Interferon Γ ◽  
Clinical Disease ◽  
Protein Abundance ◽  
Th Cells ◽  
Inflammatory Protein ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Abstract Background Chronicity of inflammatory bowel disease (IBD) is driven by reactivation of inflammatory memory CD4+ T helper (Th) cells which activate an inflammatory cascade involving innate immune cells and structural intestinal tissue cells. Because of disease heterogeneity, novel treatment strategies tailored to more precisely target the patient’s individual immune defect are required to prevent disease reactivation. We hypothesize that analysis of changes in circulating inflammatory protein abundance combined with phenotyping of circulating Th cells allow to dissect underlying immune pathogenesis and we aim to stratify pediatric IBD patients accordingly. Methods We performed plasma analysis of 92 inflammatory proteins in a cohort of pediatric IBD patients (CD: n=62; UC/IBD-U: n=20), patients with suspicion of IBD but negative diagnosis (n=13) and age-matched healthy controls (HC: n=30). Peripheral blood was obtained at diagnosis and after induction treatment (t=10–14 weeks). Plasma protein concentrations were assessed with Olink Proximity Extension Assay technology® and Th cells were analyzed with flow cytometry. Samples were clustered using hierarchical clustering with Ward linkage. Differential protein abundance was assessed with t-tests at t=0 and a mixed effect model after treatment. Results Thirty-six plasma proteins discriminated pediatric IBD patients from HC. CD and UC/IBD-U patients shared increased abundance of 17 proteins amongst which interleukin-6 and oncostatin-M. Increased abundance of the Th1 cytokine interferon-γ was strictly associated with CD while Th17-associated interleukin-17A was significantly more abundant in UC/IBD-U. Hierarchical clustering of plasma protein profiles discriminated 2 clusters of UC patients with different clinical disease activity and disease extent. In CD, three patient clusters were identified. CD#1 patients had lower clinical disease activity, lower C-reactive protein and higher blood albumin concentrations. Clusters CD#2 and CD#3 had comparable clinical parameters. CD#3 patients had higher abundance of 14 proteins associated with neutrophil function and interferon-γ signaling while CD#2 patients had a marked increase in frequencies of activated (HLA-DR+) memory Th cells. The three CD clusters responded differently to therapy with CD#1 patients exhibiting only a few changes, CD#2 patients showing intermediate modulation and CD#3 patients exhibiting more modulated proteins and greater fold changes. Conclusion Combined plasma immune protein and circulating Th cell profiling discriminates subgroups of pediatric IBD patients during active disease which differ in their response to therapy. Abbreviations: CD: Crohn’s disease; UC: ulcerative colitis; IBD-U: IBD-unclassified.

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