Prophylaxis in Crohns disease after surgical intervention

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Prophylaxis in Crohns disease after surgical
intervention

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• Dr. ALI KHALIL

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Surgical indications

• gt 50 of Patients with ileal or ileocolonic
  crohns disease undergo resection of the diseased
  bowel because of complications including
• Stenosis
• Abcess
• Fistula
• Intractable disease

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Complications of Crohns Disease
Crohns Strictures
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Complications of Crohns Disease
Crohns Fistulae
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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 gt 30 years
• - duration of disease gt
  5 years
• - use of corticosteroids
  gt 6 months
• - smoking habits
• - chronic activity

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Crohns 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

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Crohns Disease - Treatment

• Conventional therapies
• Aminosalicylates
• Corticosteroids/Budesonide
• Immunomodulators
• Antibiotics
• Anti-metabolites
• Biologic Modifiers

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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
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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 crohns disease after surgical
  resection
• The symptomatic reccurence rate in the treatment
  group was 31 compared with 41 in the placebo
  group ( p0,031)

Mcleod et al, gastroenterology 1995
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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
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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
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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
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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
  crohns disease

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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
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Patients with recurence
Placebo
Budesonide
percentage of patients with macroscopic
recurrence of inflammation in the neoterminal
ileum
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Patients with recurence
Placebo
Budesonide
percentage of patients with macroscopic
recurrence of inflammation of anastomosis
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Endoscopy score
Placebo
Budesonide
Endoscopy score in the neoterminal ileum
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Endoscopy score
Placebo
Budesonide
Endoscopy score at anastomosis
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Immunomodulators6-Mercaptopurine (6-MP)

• Randomized study, double-blind
• 131 patients
• 6-MP (50mg), mesalamine (3g) or placebo daily

Stephen et al, gastroenterology 2004
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Clinical recurrence
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Endoscopic recurrence
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Radiographic recurrence
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ImmunomodulatorsAzathioprine

• 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
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ImmunomodulatorsConclusion

• ? 6-MP, 50mg daily was more effective than
  placebo at preventing post-operative recurrence
  of crohns 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

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AntibioticsMetronidazole

• 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
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AntibioticsOrnidazole

• 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
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AntibioticsConclusions

• ? Metronidazole therapy for 3 months decreased
  the severity of early recurrence of crohns
  disease after resection and seems to delay
  symptomatic recurrence
• Ornidazole 1g/day is effective for the
  prevention of recurrence of Crohns disease after
  ileocolonic resection
• Ornidazole have a better safety profile

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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
  crohns disease
• Budesonide 6mg/ day, may be more effective in
  patients with high disease activity as a primary
  indication for surgery