Is there a role for mesalamine treatment in IBD? PRO Peter Laszlo LAKATOS Semmelweis University, 1st Department of Medicine Budapest

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1 Is there a role for mesalamine treatment in IBD? PRO Peter Laszlo LAKATOS Semmelweis University, 1st Department of Medicine Budapest

2 June 13-15, 2013 Berlin, Germany Prof. Peter Lakatos Semmelweis University 1st Department of Medicine Is there a role for mesalamine in the treatment of IBD - Pro Disclosure of Potential Conflict of Interest Consultant Lecture Abbott Hungary MSD Hungary Ferring Hungary Ferring Abbott

3 Objectives To discuss the role of mesalamine therapy in UC active disease maintenance special situation CD active disease maintenance special situation

4 5ASAs and ulcertive colitis

5 5ASA in ulcerative colitis active disease Dignass A JCC 2012

6 Dignass A JCC 2012 Van Assche G JCC ASA in ulcerative colitis maintenance therapy

7 Disease course in UC 59% 1% 0 Years 10 Curve 1: Remission or mild severity of intestinal symptoms after initial high activity 9% 0 Years 10 Curve 2: Increase in the severity of intestinal symptoms after initial low activity 31% 0 Years 10 Curve 3: Chronic continuous symptoms 0 Years 10 Curve 4: Chronic intermittent symptoms Henriksen Inflamm Bowel Dis 2006;12:543

8 5ASAs and Crohn s disease

9 Inflammation is ongoing and resulting tissue damage is cumulative Digestive damage Progression of digestive damage and inflammatory activity in a theoretical patient with Crohn s disease Stricture Fistula / abscess Surgery Stricture Inflammatory activity (CDAI, CDEIS, CRP) Disease onset Pre-clinical Diagnosis Clinical Early disease CDAI: Crohn s disease activity index; CDEIS: Crohn s disease endoscopic index of severity; CRP: C-reactive protein Pariente B, et al. Inflamm Bowel Dis 2011

10 Proposed treatment strategies in CD severe IMMS + TNF antagonist IMMS + TNF antagonist IMMS + TNF antagonist Corticosteroids + IMMs moderate Corticosteroids Corticosteroids + IMMS Conventional step-care Accelerated step-care Early top-down Ordas I Gut 2011 o o o Tailured therapy! Smoking cessation Appropriate timing of elective surgery

11 However

12 Disease course in CD 373 CD Phenotypes 8 years after diagnosis in an inception cohort Copenhagen only 5ASA, steroids & surgery available Agressive: Relapse every year Moderate: Half of the years in remission Indolent: Relapse free since diagnosis or majority of the years in remission Munkholm P et al. Scand J Gastroenterol 1995;30:699

13 Disease course in CD 43% (n=85) 3% (n=6) 0 Years 10 Curve 1: Remission or mild severity of intestinal symptoms after initial high activity 19% (n=37) 0 Years 10 Curve 2: Increase in the severity of intestinal symptoms after initial low activity 32% (n=63) 0 Years 10 Curve 3: Chronic continuous symptoms 0 Years 10 Curve 4: Chronic intermittent symptoms Solberg IC, et al. Clin Gastro Hepatol 2007;5:

14 Indolent course Crohn s disease active 8% 48% inactive 44% D sis Munkholm P, et al. Scand J Gastroenterol 1995:30: Years after the diagnosis

15 5ASA in active disease mild-to-moderate activity

16 Patients (%) 5ASAs a historical perspective Sulphasalazine Mesalazine Sulphapyridine 30 * * * 0 Clinical Sigmoidoscopic Histological Means of assessing improvement (after Azad Khan et al, 1977) * = Patients showing pronounced improvement (%)

17 Efficacy of 5ASA in CD: the Coppenhagen experiance 168 CD 1 st 5ASA course, monotherapy 1-49 year after diagnosis Duricova D. JCC 2010

18 Oral 5-ASA in mild-to-moderate CD? Hanauer SB Clin Gastro Hepatol 2004;2:379

19 Anti TNFs in active CD Design: Randomized Reponders Randomization & therapy Peyrin-Biroulet L Clin Gastro Hepatol 2008;6:644

20 Oral 5ASA in moderate CD? (CDAI !) Prantera C Gastroenterology 1999;116:521

21 5ASA and maintenance

22 5ASA in Medically induced remission

23 5ASA for maintenance Mesalazine (750mgx4) vs placebo Maintenance of placebo after 48 week (n=293) Relapse rate mesalazine =25% Placebo = 36%, p=0.056 BUT Ileocolonic disease: 21% vs 41%, p=0.018 Females : 19% vs 41%, p=0.003 Sutherland LR Gastroenterology 1997;112:

24 5ASA in medically induced remission metaanalysis p=0.06

25 5ASA in medically induced remission PRO Steinhart AH Aliment Pharmacol Ther 2007;25:

26 5ASA in medically induced remission CON Olsalazin! Akobeng AK Cohrane Database Syst Rev 2005 Art No CD003715

27 5ASA in active CD ECCO Statements Dignass A JCC 2010

28 5ASA in Surgical induced remission PRO Steinhart AH Aliment Pharmacol Ther 2007;25:

29 5ASA in Surgical induced remission Patients preference Kenedy ED Inlfamm Bowel Dis 2008;14:224

30 5ASA in special situations

31 Meta-analysis Pregnancy

32 Cancer Jess T. AJG 2006

33 Cancer prevention in CD? Both surgery 5ASA either surgery Or 5ASA no surgery Or 5ASA Piton G. AJG 2008 Munkholm P. EGHR 2012

34 5ASA in clinical practice

35 5ASA use in CD in the everyday clinical practice Gearry RB Inflamm Bowel Dis 2007;13:1009

36 5ASA use in CD in Hungary Veszprem population-based inception cohort , n=506, median follow-up: 13 years 5-ASA SP or mesalazine use at any time point: 75.2% Lakatos IBD 2011

37 Safety

38 Adverse events Side effects are not significantly different from placebo NNH=100 Hanauer SB et al Loftus E. APT 2004 Adverse renal events are very low (<0.05%) Van Staa. Gastro 2004

39 Conclusions & take home message 5ASA has a place in the therapeutic armamentarium in IBD It is the first line induction and maintenance drug in mild-to-moderate UC Effective in induction and maintenance of remission in mild (to moderate) CD, especially in colonic disease may prevent postoperative recurrence Has a chemopreventive effect against CRC Excellent safety profile Special situations (pregnancy)