1. “Antibiotics and corticosteroids: Indications and approaches”
Raymond Cross, M.D., M.S., AGAF
Associate Professor of Medicine
Director of the Inflammatory Bowel Disease Program
University of Maryland School of Medicine
Co-Director, Digestive Health Center
University of Maryland Medical Center
12/4/14

2. Goals of Therapy Induce remission Maintain steroid-free remission
Enhance quality of life
Achieve mucosal healing
Prevent/treat complications of disease
Avoid short and long term toxicity of therapy

3. PGA of Disease Activity
Remission: No symptoms
Mild disease activity: No limitations in activity (i.e., not missing work, not canceling social engagements)
Moderate disease activity: Impaired activity (i.e., missing days of work, canceling some social engagements)
Severe disease activity: Severely impaired activity (i.e., housebound, bathroom bound, hospitalized)

4. AMINOSALICYLATES

5. AMINOSALICYLATE DISTRIBUTION

6. 5-ASA Content of 5-ASA Preparations
Generic
Trade
5-ASA Content (%)
Usual Dosage
Amount of 5-ASA Delivered
Sulfasalazine
Azulfidine, Azulfidine EN, Sulfazine, Sulfazine EC 38
4 g
1.6 g
Mesalamine
Apriso, Asacol HD, Canasa, Delzicol, Lialda, Pentasa, Rowasa, SfRowasa,
100 g
Balsalazide
Colazal, Giazo 35 g
1.2 g-2.4 g
Olsalazine
Dipentum
1 g
Adapted from: Ulcerative Colitis-The Complete Guide to Medical Management (Lichtenstein)

7. Oral 5-ASA Are Effective For Induction Of Remission In UC
Cochrane Database of Systematic Reviews 17 OCT 2012 DOI: / CD pub3

8. No Difference in Remission Rates between 5-ASA Preparations
Cochrane Database of Systematic Reviews 17 OCT 2012 DOI: / CD pub3

9. High Dose Oral 5-ASA is Not More Effective at Induction of Remission than Moderate Dose in UC
Cochrane Database of Systematic Reviews 17 OCT 2012 DOI: / CD pub3

10. High Dose 5-ASA May Be More Effective in Patients Exposed to Prior Therapy
Sandborn, W. J., et al. (2009). Gastroenterology

11. Efficacy of Once vs. Twice Daily 5-ASA for Induction of Remission in UC
Lichtenstein, G. R., et al. (2007). Clin Gastroenterol Hepatol

12. ORAL VERSUS RECTAL MESALAMINE VERSUS COMBINATION THERAPY IN ACTIVE DISTAL ULCERATIVE COLITIS

13. Dose of Oral 5-ASA Not Important For Maintenance of Remission in UC
Cochrane Database of Systematic Reviews 17 OCT 2012 DOI: / CD pub3

14. 5-ASA Associated with Small Clinical Benefit in Crohn’s disease
Pentasa reduces CDAI compared to placebo
Clinical Gastroenterology and Hepatology 2004; 2:
Copyright © 2004 American Gastroenterological Association Terms and Conditions

15. 5-ASA is Not Protective Against Colon Cancer in IBD
Meta-analysis of non-referral populations
4 studies included
Association between ≥ 1 year of 5-ASA use and neoplasia
aOR 0.95 ( )
Significant heterogeneity among trials
Nguyen, G. C., et al. (2012). Am J Gastroenterol

16. Budesonide MMX 9 mg Effective at Induction of Remission in UC*
*p<0.05
Sandborn et al, Gastroenterology. 2012

17. Budesonide Foam Effective for Treatment of UP and UPS
Sandborn, WJ. ACG 2014

18. ORAL BUDESONIDE IN ACTIVE CROHN’S DISEASE

19. CD Maintenance Therapy with Budesonide**
p<0.01 *
Sandborn, W et al. Am J Gastroenterol 2005

20. Long Term Use of Budesonide is Well Tolerated
P=0.015
P=0.007
P=0.008
P=0.011
Schoon, EJ. et al. Clin Gastroenterol Hepatol 2005

21. Corticosteroid Therapy for UC
Immediate
Outcome*
(n = 63)
Complete
Remission
54%
(n = 34)
Partial
Remission
30%
(n = 19) No
Response
16%
(n = 10)
Prolonged Response
49%
(n = 31)
Steroid Dependent
22%
(n = 14)
Surgery
29%
(n = 18)
1-Year
Outcome
(n = 63)
*30 days after initiating corticosteroid therapy
Faubion, W., et al. Gastroenterology 2001

22. Corticosteroid Therapy for Crohn’s Disease
Immediate
Outcome*
(n = 74)
Complete
Remission
58%
(n = 43)
Partial
Remission
26%
(n = 19) No
Response
16%
(n = 12)
Prolonged Response
32%
(n = 24)
Steroid Dependent
28%
(n = 21)
Surgery
38%
(n = 28)
1-Year
Outcome
(n = 74)
*30 days after initiating corticosteroid therapy
Faubion, W., et al. Gastroenterology 2001

23. IV Steroids
No need to give more than 60 mg of Methylprednisolone sodium succinate or 300 mg of hydrocortisone
Can give once daily
Response generally occurs within 5-7 days!
~60% of patients completely respond to IV steroids
Truelove, SC and Jewell, DP. Lancet 1974
Truelove, SC et al. Lancet 1978
Jarnerot, G et al. Gastroenterology 1985
Gustavsson, A et al. Am J Gastroenterol 2007

24. Use of Steroids with IFX for Induction of Remission is Highly Effective in CD
Feagan, B. G., et al. (2014). Gastroenterology

25. IV Steroids Premedication Reduces ATI in CD
Farrell, R. J., et al. Gastroenterology 2003

26. Conclusions
5-ASA is effective for induction and maintenance of remission in patients with UC
Combination of oral and topical 5-ASA more effective for distal disease
5-ASA is of marginal benefit in patients with CD
All 5-ASA are effective when given at equal dose
Moderate and high dose 5-ASA equally effective for induction of remission in UC
Once daily dosing is equally effective to split dosing (and likely associated with better adherence)

27. Conclusions (cont.)
Budesonide is effective for induction of remission in mild to moderate ileocolonic Crohn’s disease and UC
Has a limited role in maintenance of remission
Prednisone is effective at induction of remission
Poor side effect profile
No role for maintenance of remission
May be used in combination with an anti-TNF to induce remission in moderate to severe Crohn’s disease
IV steroids may be used prior to IFX to decrease ATI