P.06.20 ROLE OF TROUGH LEVELS AND ANTIBODIES TO INFLIXIMAB IN THE EVALUATION OF LOSS OF RESPONSE AND INFUSION REACTIONS TO INFLIXIMAB THERAPY IN INFLAMMATORY BOWEL DISEASE

Tenascin-C (TNC) is an extracellular matrix glycoprotein expressed in response to inflammation and tissue damage. The role of TNC in patients with inflammatory bowel disease (IBD) is not well understood. In this study, we analyzed the expression of TNC in the inflamed mucosa of patients with ulcerative colitis (UC) and Crohn’s disease (CD). Serum TNC levels were determined by the enzyme-linked immunosorbent assay (ELISA), and the levels of TNC in patients with different disease activities were compared. The expression of TNC was derived from a GEO dataset. THP-1 cells were stimulated with TNC to evaluate the proinflammatory role of TNC. We found higher TNC expression in the inflamed mucosa of patients with UC and CD compared with normal controls (NCs). TNC was mainly expressed in the stromal area of the intestinal mucosa. The median serum levels of TNC were significantly higher in UC (median 74.1 ng/ml, range 42.6–102.1 ng/ml) and CD (median 59.2 ng/ml, range 44.0–80.9 ng/ml). We also found that serum TNC levels were correlated with Mayo scores in UC and Crohn’s disease activity index (CDAI) in CD. Through GSE14580, we demonstrated that patients who were nonresponsive to infliximab treatment had higher mucosal TNC mRNA expression. High TNC mRNA expression in the inflamed intestinal mucosa was associated with poor response to infliximab therapy in patients with UC. Furthermore, THP-1 cells stimulated with TNC showed increased expression of IL-6, but not TNF-α, IL-8, MCP-1, or IL-1β. Thus, increased TNC levels may participate in the pathogenesis of IBD and may serve as a biomarker for disease activity and response to treatment with infliximab.

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The role of serum TNF-$alpha; in predicting response to infliximab therapy in patients with active inflammatory bowel disease

The American Journal of Gastroenterology ◽

10.1016/s0002-9270(01)03697-8 ◽

2001 ◽

Vol 96 (9) ◽

pp. S289 ◽

Cited By ~ 1

Author(s):

J DAVID

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Infliximab Therapy ◽

Tnf Alpha ◽

Active Inflammatory Bowel Disease ◽

Inflammatory Bowel

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

Inflammatory Intestinal Diseases ◽

10.1159/000511296 ◽

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

Background and Aims: 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. Methods: 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. Results: 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 (p = 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 (p = 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. Conclusions: 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.

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HLADQA1*05 genotype predicts anti-drug antibody formation and loss of response during infliximab therapy for inflammatory bowel disease

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.15563 ◽

2019 ◽

Vol 51 (3) ◽

pp. 356-363 ◽

Cited By ~ 6

Author(s):

Aze Wilson ◽

Celeste Peel ◽

Qian Wang ◽

Athanasios Demetri Pananos ◽

Richard B. Kim

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Antibody Formation ◽

Infliximab Therapy ◽

Loss Of Response ◽

Inflammatory Bowel

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A Study Investigating the Association of Dermatological and Infusion Reactions to Infliximab and Infliximab Trough Levels

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2015/428702 ◽

2015 ◽

Vol 29 (1) ◽

pp. 35-40 ◽

Cited By ~ 14

Author(s):

Vivian Wai-Mei Huang ◽

Neil Dhami ◽

Darryl Fedorak ◽

Connie Prosser ◽

Carol Shalapay ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Adverse Events ◽

Infliximab Therapy ◽

Blood Samples ◽

University Of Alberta ◽

Infusion Reactions ◽

Inflammatory Bowel ◽

Stable Maintenance ◽

The University ◽

Trough Levels

BACKGROUND: Although infliximab is an effective therapy for inflammatory bowel disease (IBD), it is associated with dermatological events and infusion reactions. It is not known whether a relationship between these adverse events (AEs) and infliximab trough levels (ITLs) exists.OBJECTIVES: To report the prevalence of infliximab-associated AEs in IBD patients receiving stable maintenance infliximab therapy, and to correlate ITLs with dermatological and infusion reactions to infliximab.METHODS: Adult IBD patients receiving stable maintenance infliximab therapy were recruited from the University of Alberta Infusion Clinic (Edmonton, Alberta). ITLs were measured in blood samples collected before infusion, and the patients’ records were reviewed for dermatological and infusion reactions to infliximab.RESULTS: One-quarter (18 of 71 [25.4%]) of patients experienced dermatological or infusion reactions to infliximab: nine (12.7%) dermatological events and nine (12.7%) infusion reactions. The median ITL was similar among patients with and without these AEs (7.2 μg/mL [interquartile range (IQR) 2.0 μg/mL to 13.3 μg/mL] versus 6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.648). The median ITL of patients who experienced infusion reactions (2.0 μg/mL [IQR 0.1 μg/mL to 5.7 μg/mL]) was lower than that of patients who experienced no such AEs (6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.008]) and lower than that of patients who experienced dermatological AEs (13.3 μg/mL [IQR 8.8 μg/mL to 17.4 μg/mL]; P<0.001).CONCLUSION: One-quarter of IBD outpatients receiving stable maintenance infliximab therapy experienced dermatological and infusion reactions. Low ITLs were correlated with infusion reactions, and normal or high ITLs with dermatological events.

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