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Permanent link (DOI): https://doi.org/10.7939/R3GD57

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The Role of Vitamin D in Anti-Tumor Necrosis Factor-Alpha-Induced Response in Patients with Inflammatory Bowel Disease Open Access

Descriptions

Other title
Subject/Keyword
Ulcerative colitis
Vitamin D
Anti-TNF therapy
Infliximab
Depression
Inflammatory bowel disease
Cytokines
Crohn's disease
Quality of life
Response
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Reich, Krista, M
Supervisor and department
Fedorak, Richard (Medicine)
Madsen, Karen (Medicine)
Kroeker, Karen (Medicine)
Examining committee member and department
Gramlich, Leah (Medicine)
Tsuyuki, Ross (Medicine)
Fedorak, Richard (Medicine)
Kroeker, Karen (Medicine)
Madsen, Karen (Medicine)
Department
Department of Medicine
Specialization
Experimental Medicine
Date accepted
2014-07-10T09:13:23Z
Graduation date
2014-11
Degree
Master of Science
Degree level
Master's
Abstract
Vitamin D is an important immunomodulator of the immune system and has been suggested to play a role in the pathogenesis of inflammatory bowel disease (IBD). Drugs targeting TNF-alpha are effective IBD therapies, and vitamin D has been demonstrated to suppress TNF-alpha as well as work synergistically with infliximab to reduce TNF-alpha in vitro. As a result, vitamin D may play a role in anti-TNF-induced response. The objectives of this study were to first compare the proportion of patients who achieved a clinical response in the normal vitamin D group to the proportion of patients who achieved a clinical response in the low vitamin D group at week 14; and to secondly compare clinical response rates at week 22, after the low vitamin D group was supplemented at week 14. Secondary outcomes included assessing clinical remission, C-reactive protein normalization, cytokine responses, health related quality of life, and depression at these time points. Adult Crohn’s disease and ulcerative colitis patients initiating anti-TNF therapy were invited to participate. Prior to starting anti-TNF therapy and at week 14, blood samples were collected to measure serum vitamin D, C-reactive protein, and cytokines levels and questionnaires were administered to assess clinical disease activity, depression, and quality of life. Patients low in vitamin D (serum 25(OH)D levels <75 nmol/L) were then administered a high dose (250,000-500,000 IU) of vitamin D intramuscularly within 2 weeks of their week 14-dose. Patients with normal vitamin D levels were not supplemented. Measurements of vitamin D, C-reactive protein, cytokines, clinical disease activity, depression, and quality of life were repeated 8 weeks later, prior to the patient’s week 22- dose. Clinical response at week 14 and week 22 was defined as a decrease of ≥ 3 points in the clinical disease activity scores from baseline. The proportion of patients who clinically responded at week 14 was similar between the two vitamin D groups (67% (14/21) vs. 65% (15/23), p=0.92). However, after stratifying by disease severity, there was a clinically significant higher proportion of patients in the low vitamin D group who responded at week 14 compared to the normal vitamin D group, if patients had severe disease (79% (11/14) vs. 53% (9/17), p=0.14). On the contrary, there was a trend to a higher proportion of patients in the normal vitamin D group who responded at week 14 compared to the low vitamin D group, if patients had non-severe disease (100% (4/4) vs. 44% (4/9), p=0.11). Clinical response results at week 22 were similar. Patients with low vitamin D levels and severe disease had higher serum levels of TNF-alpha, IL-6, and IL-1beta at baseline compared to patients with normal vitamin D levels and severe disease. By week 14 and week 22, cytokine levels were similar. Quality of life scores paralleled improvement in disease activity, and patients with low vitamin D levels had more cognitive depressive symptoms at the start of therapy. In conclusion, the inflammatory responses in patients with severe disease and low vitamin D levels are effectively treated with infliximab and adalimumab, and it may be that having inadequate levels of vitamin D before initiating anti-TNF therapy increases IBD patients’ sensitivity to this drug.
Language
English
DOI
doi:10.7939/R3GD57
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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