Aminosalicylates. V. Gross

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1 Aminosalicylates V. Gross

2 Antiinflammatory activity of 5-ASA Prostaglandin synthesis Leukotriene synthesis Thromboxane synthesis PAF synthesis Cytokines (IL-1, TNF) Reactive oxygen metabolites Intestinal bacteria colonic epithelium

3 5-ASA in diverticular disease Diverticulosis Symptomatic diverticular disease IBS? Diverticular colitis? Subclinic diverticulitis? Acute uncomplicated diverticulitis Recurrent diverticulitis Complicated (perforated) diverticulitis

4 5-ASA in diverticular disease Diverticulosis Symptomatic diverticular disease IBS? Diverticular colitis? Subclinic diverticulitis? Acute uncomplicated diverticulitis Recurrent diverticulitis Complicated (perforated) diverticulitis

5 Studies with 5-ASA in diverticular disease Trespi et al.: Therapeutic and prophylactic role of mesalazine (5-ASA) in symptomatic diverticular disease of the colon. Minerva Gastroenterol. Dietol. 1999;45: Tursi et al.: Long-term treatment with mesalazine and rifaximin versus rifaximin alone for patients with recurrent attacks of acute diverticulitis of colon. Digest. Liver Dis. 2002;34: Brandimarte et al.: Rifaximin/mesalazine followed by mesalazine alone is highly effective in obtaining remission of uncomplicated diverticulitis of colon. Digest. Liver Dis. 2004;36: S 202 (P0054) Giovanni et al.: Efficacy of mesalazine in the treatment of symptomatic diverticular disease. Gastroenterology 2004;126: A 253 Di Mario et al.: Efficacy of mesalazine in the treatment of symptomatic diverticular disease. Dig. Dis. Sci. 2005;50:581-86

6 Trespi et al.: Therapeutic and prophylactic role of mesalazine (5-ASA) in symptomatic diverticular disease of the colon 187 patients with acute uncomplicated diverticulitis: 1,5 g ampicillin/sulbactam bid + rifaximin 400 mg bid 7 days 166 patients 81 patients: 5-ASA 400 mg bid 8 weeks 85 patients: no further treatment Follow-up 4 years

7 Trespi et al.: Therapeutic and prophylactic role of mesalazine (5-ASA) in symptomatic diverticular disease of the colon Diverticulitis: Diverticulosis + abdominal pain, leukocytosis, increased ESR/CRP or a1-acid glycoprotein and/or fever Follow-up Patient diary (bowel movements, abdominal pain, meteorism, fever, etc.) Colonoscopy every year Lab. tests every 3 months (anemia?)

8 Trespi et al.: Further inflammatory recurrences. Kaplan Meier actuarial estimate ASA CO n Months

9 Trespi et al.: Microhemorrhagic recurrences. Kaplan-Meier actuarial estimate ASA CO 25 n Months

10 Tursi et al.: 5-ASA + rifaximin vs rifaximin in patients with recurrent acute diverticulitis 218 patients with acute diverticulitis and >2 attacks during last year: 109 patients: Rifaximin 400 mg bid + 5-ASA 800 mg tid 7 days 109 patients: Rifaximin 400 mg bid 109 patients: Rifaximin 400 mg bid + 5-ASA 800 mg tid For 7 days/month 1 year 109 patients: Rifaximin 400 mg bid For 7 days/month Symptoms, bowel habits, recurrent diverticulitis

11 Tursi et al.: 5-ASA + rifaximin vs rifaximin in patients with recurrent acute diverticulitis Diverticulitis: 218 patients with acute diverticulitis Diverticula and >2 + attacks during last year: abdominal pain or bowel disorder and/or fever and leukocytosis + increased ESR/CRP 7 days or a1-acid glycoprotein Abdominal symptoms (rated 0-4): pain, bloating, tenesmus, diarrhoe, tenderness Bowel habits: 1 year Normal (0), occasional constipation (1), recurrent const. (2), persistent const. with sub-occlusive attacks (3), persistent const. with recurrent sub-occl. attacks (4)

12 Tursi et al.: 5-ASA + rifaximin vs rifaximin in patients with recurrent acute diverticulitis Symptom free (%) ASA/Rifaximin Rifaximin Month

13 Tursi et al.: 5-ASA + rifaximin vs rifaximin in patients with recurrent acute diverticulitis Normal bowel habits (%) ASA/Rifaximin Rifaximin Month

14 Tursi et al.: 5-ASA + rifaximin vs rifaximin in patients with recurrent acute diverticulitis: Recurrence of acute diverticulitis during follow-up Recurrence N 5-ASA + Rifaximin 3 Rifaximin 16 % 2,75%* 17,98% *P<0,01

15 Di Mario et al.: 5-ASA in symptomatic uncomplicated diverticular disease 170 patients with symptomatic uncomplicated diverticular disease Diverticula (Colonoscopy or barium enema) and at least 2 of the following symptoms for M1 : 40 patients 5-ASA 400 mg bid at least 1 month: M2: 48 patients 5-ASA 800 mg bid 10 days every month for 3 months abdominal pain/discomfort, bloating, tenesmus, diarrhea, abdominal tenderness, fever, dysuria

16 Di Mario et al.: 5-ASA in symptomatic uncomplicated diverticular disease 170 patients with symptomatic uncomplicated diverticular disease R1 : 39 patients Rifaximin 200 mg bid M1 : 40 patients 5-ASA 400 mg bid R2: 43 patients Rifaximin 400 mg bid M2: 48 patients 5-ASA 800 mg bid 10 days every month for 3 months Symptom score (0-3): abdominal pain, bloating, tenesmus, diarrhea, abdominal tenderness, fever, general illness, nausea, emesis, dysuria

17 Di Mario et al.: 5-ASA in symptomatic uncomplicated diverticular disease Global symptom score 12 0 mo 0 mo mo 3 mo 3 mo 3 mo 0 mo 3 mo R1 R2 M1 M2

18 Di Mario et al.: 5-ASA in symptomatic uncomplicated diverticular disease: Symptoms, which showed a statistiacally significant difference after 3 months Frequency of symptoms (%) R1 R2 M1 M2 Pain Tenesmus Diarrhoe

19 Giovanni et al.: 5-ASA in symptomatic uncomplicated diverticular disease 248 patients with symptomatic uncomplicated diverticular disease (diverticula + >1 symptom for at least 1 month R1 : 57 patients Rifaximin 200 mg bid M1 : 60 patients 5-ASA 400 mg bid R2: 69 patients Rifaximin 400 mg bid M2: 62 patients 5-ASA 800 mg bid 10 days every month for 1 year Symptom score (0-3): abdominal pain, bloating, tenesmus, diarrhea, abdominal tenderness, fever, general illness, nausea, emesis, dysuria

20 Giovanni et al.: 5-ASA in symptomatic uncomplicated diverticular disease Lower global symptom score R1+R2 M1+M2 3 months 6 months 12 months P<0,0001 P<0,0001 P<0,005

21 Summary Study Disease Treatment Aim Trespi 1999 Acute diverticulitis 5-ASA vs no tx. for 8 weeks Recurrence 4 years Tursi 2002 Recurrent acute diverticulitis 5-ASA/rifaximin vs rifaximin 7 d/ mo for 12 mos Symptoms, bowel habits, recurrence 1 year Brandimarte 2004 Acute diverticulitis 5-ASA for 8 wks Recurrence 8 weeks Giovanni 2004 Di Mario 2005 Symptom. diverticular disease 5-ASA vs rifaximin 10 d/ mo for 3-12 mos Symptom score 3-12 months

22 Summary Study Recurrence Random. Placebo 5-ASA (vs Co) controlled Trespi 15% (vs 46%) yes no 1999 Tursi 3% (vs 18%) yes no 2002 Brandimarte ,22% no no Giovanni 2004 Di Mario 2005 Lower symptom score with 5-ASA yes no

23 Conclusion 5-ASA for long-term intermittent treatment of symptomatic diverticular disease or prevention of recurrence of diverticulitis Randomised placebo-controlled trials recommended

Aminosalicylates. Giovanni Barbara. Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna, Italy ( )

Aminosalicylates. Giovanni Barbara. Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna, Italy ( ) Aminosalicylates Giovanni Barbara Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna, Italy (1088 2016) Colonic Diverticula, a Painless Ageing Change? 20% develop symptoms