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Prophylaxis in Crohn’s disease after surgical intervention
Dr. ALI KHALIL
Surgical indications
> 50 % of Patients with ileal or ileocolonic crohn’s disease undergo
resection of the diseased bowel because of complications
including:
• Stenosis
• Abcess
• Fistula
• Intractable disease
Complications of Crohn’s Disease
Crohn’s Strictures
Complications of Crohn’s Disease
Crohn’s Fistulae
Recurrence of the disease
• Recurrence can be demonstrated endoscopically in 73% - 93% of patients at 1 year
• at the site of resection
• Approximately 50% of patients requierd repeat surgery within 10 years
• Risk factors: - age > 30 years
- duration of disease > 5 years
- use of corticosteroids > 6 months
- smoking habits
- chronic activity
Crohn’s diseaseTreatment Goals
• Diagnosis and prompt therapeutic response
• Induction of complete remission
• Maintenance of clinical remission
• Prevent recurrence of disesase in disease-free segments of the
bowel after surgery
• Low side-effect profile to enhance compliance
Crohn’s Disease - Treatment
Conventional therapies:
• Aminosalicylates
• Corticosteroids/Budesonide
• Immunomodulators
• Antibiotics
• Anti-metabolites
• Biologic Modifiers
AminosalicylatesMesalamine (1)
• A meta-analysis of 15 randomised controlled trials
• 2097 patients
• The mesalamine significantly reduced the risk of symptomatic
relapse
• The benefits are mainly observed in the post surgical setting
« confidence interval (–21,8% to 4,5% )
Camma C et al, gastroenterology 2001
AminosalicylatesMesalamine (2)
• Randomisad controled trial
• 163 patients
• 1,5 g of (Rowasa and salofalk) twice a day for 8 weeks
• Mesalamine is effective in decreasing the risk of reccurent
crohn’s disease after surgical resection
• The symptomatic reccurence rate in the treatment group was
31 % compared with 41 % in the placebo group ( p=0,031)
Mcleod et al, gastroenterology 1995
AminosalicylatesMesalamine (3)
• Double-blind multicenter clinical trial
• 3g/day of Pentasa , 12 months of treatment
• 67 patients
• The overall rate of severe endoscopic reccurence was 24%
in the mesalamine group and 56% int the placebo group after 1
year
Brignola et al, gastroenterology 1995
AminosalicylatesMesalamine (4)
• Prospective, double-blind, multicenter study
• 4g/day Pentasa vs placebo continued for 18 months
• 318 patients
• 10 days after resection
• Relapse after 18 months: 24,5% in group mesalamine
31,4% in placebo group
• Some relapse-preventing effect was found in patients was isolated small bowel disease
Lochts et al, gastroenterology 2000
AminosalicylatesMesalazine
• A multicenter randomized control trial
• 110 patients
• 2,4 g Asacol/day vs no treatment at all
• Colonoscopy and ileoscopy at 6 months and yearly therafter
• Over 2 year period: prevent 39 % of all reccurences and 55%
of the severe reccurences
Caprilli et al, aliment pharmacol ther 1995
AminosalicylatesConclusion
3 studies showed that mesalamine is effective in decreasing the risk of reccurence
One study showed that mesalamine did not significantly affect the postoperative course of crohn’s disease
CorticoïdesBudesonide
• A double-blind randomized trial
• 129 patients
• 6 mg/day or placebo within two weeks from surgery
• The frequency of endoscopic reccurrence did not differ between the groups
at 3 and 12 months
• In patients with disease activity as indication for surgery, the endoscopic
reccurrence rate at the anastomosis was lower in the budesonide group
• But not in patients with fibrostenosis as indication for surgery
Hellers et al, gastroenterology 1999
percentage of patients with macroscopic recurrence of inflammation in the neoterminal ileum
BudesonidePlacebo
Patients with recurence
Patients with recurence
percentage of patients with macroscopic recurrence
of inflammation of anastomosis
PlaceboBudesonide
Endoscopy score
BudesonidePlacebo
Endoscopy score in the neoterminal ileum
Endoscopy score
Endoscopy score at anastomosis
BudesonidePlacebo
ImmunomodulatorsImmunomodulators6-Mercaptopurine (6-MP)6-Mercaptopurine (6-MP)
• Randomized study, double-blind• 131 patients• 6-MP (50mg), mesalamine (3g) or placebo daily
6-MP Mesalamine Placebo
Clinical recurrence
50% 58% 77%
Endoscopic recurrence
43% 63% 64%
Radiographic recurrence
33% 46% 49%
Stephen et al, gastroenterology 2004
Clinical recurrenceClinical recurrence
Endoscopic recurrenceEndoscopic recurrence
Radiographic recurrenceRadiographic recurrence
ImmunomodulatorsImmunomodulatorsAzathioprineAzathioprine
• Comparative trial
• 142 patients
• Azathioprine (2 mg/kg/day) and mesalamine (3 g/day) for 24
months
• Relapse was experienced in 17 patients (34%) receiving
azathioprine and 28 (46%) receiving mesalamine but the
difference was not significant
Ardizzone et al, gastroenterology 2004
ImmunomodulatorsImmunomodulatorsConclusionConclusion
6-MP, 50mg daily was more effective than placebo at preventing post-operative recurrence of crohn’s disease and should be considered as a maintenance therapy after ileocolic resection
The difference was not significant between azathioprine and mesalamine
More placebo-controlled studies of recurrence prevention with immunosuppressives are necessary
Higher risk of toxicity
AntibioticsAntibioticsMetronidazoleMetronidazole
• A double-blind controlled trial
• 60 patients
• Metrornidazole 20mg/kg/day or placebo continued for 3months
• At 12 weeks, 75 % of patients in the placebo group had recurrent lesions in
the neoterminal ileum as compared with 52% in the metronidazole group
• The incidence of endoscopic recurrence was significantly reduced by
metronidazole as compared with placebo
Rutilements et al, gastroenterology 2005
AntibioticsAntibioticsOrnidazoleOrnidazole
• A double-blind randomized trial
• 80 patients
• Ornidazole 1 g/day or placebo continued for 1 year within 1week
of resection
• Clinical recurrence rate at 1 year from 37.5% in placebo group to
7.9% in the ornidazole group
• Endoscopic recurrence was reduced from 79% in Placebo to 53.6% in the ornidazole group
Rutgeerts et al, gastroenterology 2005
AntibioticsAntibioticsConclusionsConclusions
Metronidazole therapy for 3 months decreased the severity of early recurrence of crohn’s disease after resection and seems to delay symptomatic recurrence
Ornidazole 1g/day is effective for the prevention of recurrence of Crohn’s disease after ileocolonic resection
Ornidazole have a better safety profile
Summary
• Mesalamine 3g/day, 12 months of treatment within two weeks from surgery is considered as first choice treatment
• Immunomodulators should be considered as a maintenance therapy after ileocolic resection
• Ornidazole 1g/day, 3-6 months of treatment, is effective to prevent posoperative recurrence of crohn’s disease
• Budesonide 6mg/ day, may be more effective in patients with high disease activity as a primary indication for surgery