Antibiotics and risk of new onset inflammatory bowel disease a meta analysis
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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
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


Disclosures
Disclosures Disease:

Nothing to Disclose


Background
Background Disease:

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)


Study aims
Study Aims Disease:

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


Methodology
Methodology Disease:

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.


Methodology1
Methodology Disease:

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.


Search results
Search Results Disease:

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


Case control studies
Case-Control Studies Disease:

* provided extra data

Pediatric studies highlighted

1. Wells et al. Accessed at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.


Cohort studies
Cohort Studies Disease:

* 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.


Included studies
Included Studies Disease:

  • 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


Antibiotic exposure associated with increased overall risk of new onset ibd
Antibiotic exposure associated with increased overall risk of new onset IBD

(CD)

(UC)

I2 = 82.35, p = 0.00


Antibiotic exposure and risk of new onset ibd in adults and children
Antibiotic exposure and risk of of new onset IBD 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



Antibiotic exposure and risk of new onset cd in adults and children
Antibiotic exposure and risk of onset CD 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



Antibiotic exposure and risk of new onset uc in adults and children
Antibiotic exposure and risk of new onset UC 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



Limitations
Limitations risk of new onset IBD

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


Summary
Summary risk of new onset IBD

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


Discussion
Discussion risk of new onset IBD

  • 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.


Thank you
Thank You risk of new onset IBD

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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