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Antibiotics and Risk of New Onset Inflammatory Bowel Disease: A Meta-Analysis

Antibiotics and Risk of New Onset Inflammatory Bowel Disease: A Meta-Analysis. Ryan Ungaro 1 , Charles Bernstein 2 , Richard Gearry 3 , Anders Hviid 4 , Kaija-Leena Kolho 5 , Matthew Kronman 6 , Souradet Shaw 2 , Herbert Van Kruiningen 7 , Jean-Frédéric Colombel 1 , Ashish Atreja 1

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Antibiotics and Risk of New Onset Inflammatory Bowel Disease: A Meta-Analysis

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  1. Antibiotics and Risk of New Onset Inflammatory Bowel Disease: A Meta-Analysis Ryan Ungaro1, Charles Bernstein2, Richard Gearry3, Anders Hviid4, Kaija-Leena Kolho5, Matthew Kronman6, Souradet Shaw2, Herbert Van Kruiningen7, Jean-Frédéric Colombel1, Ashish Atreja1 2013 CCFA Advances in Inflammatory Bowel Diseases Conference 1. Ichan School of Medicine at Mount Sinai, New York, NY 2. University of Manitoba, Winnipeg, Canada 3. University of Otago, Christchurch, New Zealand 4. Statens Serum Institut, Coopenhagen, Denmark 5. University of Helsinki, Helsinki, Finland 6. Seattle Children’s Hospital, Seattle, Washington 7. University of Connecticut, Storrs, Connecticut

  2. Disclosures Nothing to Disclose

  3. Background Medications emerging as risk factor for IBD Antibiotics may increase risk of CD and UC1 However some studies have found no association2,3 Few studies have reported risk associated with specific antibiotic classes 1. De Vroey et al. Am J Gastroenterol. 2010;105(12) 2. Castiglione F et al. J Crohns Colitis. 2012;6(3) 3. Van Kruiningen et al. Inflamm Bowel Dis. 2005;11(4)

  4. Study Aims 1. To examine antibiotic use as a risk factor for new onset IBD, CD and UC 2. To evaluate if effect of antibiotics different in children versus adults 3. To determine IBD risk with specific antibiotic classes

  5. Methodology Meta-analysis of Observational Studies in Epidemiology (MOOSE)1 Search strategy Medline, Embase and Cochrane databases Search keywords: Inflammatory bowel disease, Crohn’s disease, ulcerative colitis, antibiotics, penicillin, cephalosporin, tetracycline, fluoroquinolone, macrolide, sulfonamide, metronidazole 1. Stroup DF, et al. JAMA 2000;283.

  6. Methodology Inclusion criteria Cohort or case-control Data on exposure to antibiotics prior to new diagnosis of IBD (CD, UC, or both) Data collection Two reviewers extracted data Authors contacted if data not available in published manuscript (7 studies) Data analysis Random-effects model to determine overall pooled estimates and 95% confidence intervals (CI) The Newcastle-Ottawa Scale (NOS) to assess study quality1 1. Wells et al. Accessed at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

  7. Search Results 4508 Citations Retrieved 2558 from Pubmed 1798 from Embase 149 from Cochrane 3 from Backward Snowballing 1234 Review Articles Excluded 3274 Original Articles 3259 Articles Excluded by Title and Abstract Review 5 Studies Excluded After Full Text Review • 3 used surrogate for antibiotic use • 1 without controls • 1 insufficient data available 16 Original Articles 11 Articles Included • 8 Case-Control • 3 Cohort

  8. Case-Control Studies * provided extra data Pediatric studies highlighted 1. Wells et al. Accessed at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

  9. Cohort Studies * provided extra data Pediatric studies highlighted IBDU = IBD, type unclassified 1. Wells et al. Accessed at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

  10. Included Studies • 11 total studies with 7,208 patients diagnosed with IBD • 3,937 patients with CD • 3,207 patients with UC • 64 patients with IBDU • Majority studies (9 of 11)explicitly excluded some time period prior to new diagnosis of IBD • Range from 3.9 months to 4 years • Limit confounding by diagnostic delay IBDU = IBD, type unclassified

  11. Antibiotic exposure associated with increased overall risk of new onset IBD (CD) (UC) I2 = 82.35, p = 0.00

  12. Antibiotic exposure and risk of new onset IBD in adults and children Adults OR 1.431 (95% CI 1.116-1.834) I2 = 90.07, p = 0.00 Children OR 1.894 (95% CI 1.237-2.989) (CD) (UC) I2 = 48.78, p = 0.099 I2 = 48.78, p = 0.099

  13. Antibiotic exposure associated with increased risk of new onset CD I2 = 84.87, p = 0.00

  14. Antibiotic exposure and risk of new onset CD in adults and children Adults OR 1.565 (95% CI 1.177-2.081) I2 = 89.97, p = 0.00 Children OR 2.747 (95% CI 1.723-4.379) I2 = 0.00, p = 0.63

  15. Antibiotic exposure NOT associated with increased risk of new onset UC I2 = 47.41, p = 0.07

  16. Antibiotic exposure and risk of new onset UC in adults and children Adults OR 1.058 (95% CI 0.851-1.316) I2 = 72.71, p = 0.012 Children OR 1.112 (95% CI 0.773-1.602) I2 = 0.00, p = 0.87

  17. Most classes of antibiotics are associated with increased risk of new onset IBD

  18. Limitations Data compiled from retrospective studies Questionnaire studies subject to recall bias Range in the quality of studies (based on QOS scale) Significant heterogeneity in certain analyses Different antibiotic exposure exclusion time periods

  19. Summary Antibiotic exposure increases odds of new diagnosis IBD Antibiotic use increases risk new onset CD but not UC CD risk greatest in children Most antibiotic classes associated with IBD Penicillin not associated Metronidazole and quinolones most strongly associated

  20. Discussion • Antibiotics may increase IBD risk by altering microbiome • Alternatively, association may be surrogate marker for increased risk infections in CD 1. Manichanh C et al.Nat Rev Gastroenterol Hepatol. 2012;;9(10). 2. Perez-Cobas et al. Gut. 2013; 62(11). 3. Gradel KO et al. Gastroenterology. 2009;137.

  21. Thank You Ashish Atreja Jean-Frederic Colombel Charles Bernstein Richard Gearry Anders Hviid Kaija-Leena Kolho Matthew Kronman Souradet Shaw Herbert Van Kruiningen Crohn’s and Colitis Foundation of America

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