Usage
  • 10 views
  • 2 downloads

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

  • Author / Creator
    Reich, Krista, M
  • 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.

  • Subjects / Keywords
  • Graduation date
    2014-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3GD57
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Department of Medicine
  • Specialization
    • Experimental Medicine
  • Supervisor / co-supervisor and their department(s)
    • Fedorak, Richard (Medicine)
    • Madsen, Karen (Medicine)
    • Kroeker, Karen (Medicine)
  • Examining committee members and their departments
    • Fedorak, Richard (Medicine)
    • Kroeker, Karen (Medicine)
    • Madsen, Karen (Medicine)
    • Tsuyuki, Ross (Medicine)
    • Gramlich, Leah (Medicine)