Once Daily Dosing for Induction and Maintenance of Remission in Ulcerative Colitis

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1 Once Daily Dosing for Induction and Maintenance of Remission in Ulcerative Colitis John K. Marshall MD MSc FRCPC AGAF Division of Gastroenterology McMaster University JKM 2014

2 Svartz N. Acta Med Scand 1942;110:577

3 Treatment of Ulcerative Colitis Severe Moderate Mild Proximal Surgery Anti-TNFα Cyclosporine IV Steroids Infliximab, IV/PO Steroids 6MP/Azathioprine Aminosalicylates Topical Corticosteroids Aminosalicylates Oral Rectal Distal

4 Sulfasalazine: Dose-Dependent Efficacy and Toxicity Response Toxicity 1g 2g 3g 4g Das K. N Engl J Med 1973;289:491-4

5 Approved Induction Regimens for Oral 5ASA (Canada) Product: Asacol TM Mezavant TM Pentasa TM Salofalk TM Salazopyrin TM Dose Frequency: Divided Doses OD QID TID-QID BID-QID

6 Patient Adherence in Ulcerative Colitis % of Patients Adherent % 40% - 60% 40% 20 0 Clinical Trials Communitybased Trials Patients in Remission Kane SV. Aliment Pharmacol Ther 2006;23:577-85

7 Predictors of Non-Adherence to 5ASA in Ulcerative Colitis Kane SV. Aliment Pharmacol Ther 2010;32:1051-8

8 Reasons for Non-Compliance: CCFA Survey % of Respondents Internet survey: N=944 noncompliant UC patients 90% just forgot to take their medication Loftus EV. Inflamm Bowel Dis 2006;12:

9 Oral 5ASA for Induction of Remission of Ulcerative Colitis Literature search: MEDLINE, EMBASE, Cochrane Library from inception to 19/3/2014 Criteria for inclusion: Prospective, parallel-design RCT: Adult subjects Duration 4 weeks Oral 5ASA vs. placebo, sulfasalazine or other 5ASA Primary endpoint: Proportion who fail to enter complete global or clinical remission (as defined by study authors) by ITT analysis Feagan BG. Cochrane Database Syst Rev 2014a

10 Oral 5ASA for Induction of Remission of Ulcerative Colitis 51 eligible studies (N=8508) 15 5ASA vs. Placebo 17 5ASA vs. Sulfasalazine 12 5ASA vs. other 5ASA 10 5ASA dose ranging 4 trials comparing once-daily vs. conventional dosing: Kamm. Gastroenterology 2007;132:66-75 Lichtenstein. Clin Gastroenterol Hepatol 2007;5: Kruis. Gut 2009;58: Flourie. Aliment Pharmacol Ther 2013;37: Feagan BG. Cochrane Database Syst Rev 2014a

11 Once Daily vs. Conventional Dosing: Failure to Induce Clinical Remission Feagan BG. Cochrane Database Syst Rev 2014a

12 Oral 5ASA for Maintenance of Remission of Ulcerative Colitis Literature search: MEDLINE, EMBASE, Cochrane Library from inception to 19/3/2014 Criteria for inclusion: Prospective, parallel-design RCT: Adult subjects Duration months Oral 5ASA vs. placebo, sulfasalazine or other 5ASA Primary endpoint: Endoscopic or clinical relapse (as defined by study authors) by ITT analysis Feagan BG. Cochrane Database Syst Rev 2014b

13 Oral 5ASA for Maintenance of Remission of Ulcerative Colitis 39 eligible studies (N=7301) 7 trials of 5ASA vs. Placebo 12 trials of 5ASA vs. Sulfasalazine 5 trials of 5ASA vs. other 5ASA 8 trials of 5ASA dose ranging 10 trials comparing once-daily vs. conventional dosing: Kane. Clin Gastroenterol Hepatol 2003;1:170-3 Kamm. Gut 2008;57: Kane. Pat Pref Adherence 2008;2:253-8 Dignass. Clin Gastroenterol Hepatol 2009;7:762-9 Prantera. Aliment Pharmacol Ther 2009;30: Sandborn. Gastroenterology 2010;138: Hawthorne. Gastroenterology 2011;140:S65 Kruis. Aliment Pharmacol Ther 2011;33: D Haens. Am J Gastroenterol 2012;107: Wantanabe. Infamm Bowel Dis 2013; 19: Feagan BG. Cochrane Database Syst Rev 2014b

14 Once Daily vs. Conventional Dosing: Relapse at 12 Months Feagan BG. Cochrane Database Syst Rev 2014b

15 Once Daily vs. Conventional Dosing Failure to Adhere (Maintenance) Feagan BG. Cochrane Database Syst Rev 2014b

16 Once Daily vs. Conventional Dosing: Adverse Events (Maintenance) Feagan BG. Cochrane Database Syst Rev 2014b

17 Compliance* with Oral 5ASA: Retrospective Analysis of RAMQ 5 ASA Overall Lachaine J. BMC Gastroenterol 2013;13:23

18 5ASA Suppositories OD vs. TID for Active Ulcerative Proctitis (N=408, single-blind, 6 weeks) Andus T. Inflamm Bowel Dis 2010;16:

19 Summary 5ASA is effective for inducing and maintaining remission in mild to moderately active ulcerative colitis Adherence to therapy for mild to moderately active ulcerative colitis is sub-optimal Once daily dosing of oral 5ASA is as effective and safe as conventional divided dosing for inducing and maintaining remission of mild to moderately active ulcerative colitis Once daily dosing of oral 5ASA may improve adherence

20 Conclusions Oral 5ASA can be dosed once daily for inducing and maintaining remission of mild to moderately active ulcerative colitis This strategy appears to applicable to 5ASA therapy as a class, and not specific to any particular formulation

21 JKM 2014 THANK YOU

Oral mesalamine formulations are first-line treatments

Oral mesalamine formulations are first-line treatments COCHRANE REVIEW Once Daily Oral Mesalamine Compared to Conventional Dosing for Induction and Maintenance of Remission in Ulcerative Colitis: A Systematic Review and Meta-Analysis Brian G. Feagan, MD, and