1 / 65

Management of Perianal Crohn ’s Disease

Management of Perianal Crohn ’s Disease. Yousif, A Qari MD, FRCPc, ABIM Department of Medicine Division of Gaseroenteroloy King Abdulaziz University Jeddah, Saudi Arabia. Perianal fistulas in CD.

huslu
Download Presentation

Management of Perianal Crohn ’s Disease

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Management ofPerianal Crohn’s Disease Yousif, A Qari MD, FRCPc, ABIMDepartment of Medicine Division of Gaseroenteroloy King Abdulaziz UniversityJeddah, Saudi Arabia

  2. Perianal fistulas in CD Perianal fistulas are a frequent manifestation of Crohn's disease that can result in significant morbidity, including scarring, faecal incontinence, and even proctectomy in up to 10–18% of patients.

  3. Long-Term Treatment of Fistulizing Crohn’s Disease • Epidemiology/Classification • Therapeutic goals • Conventional therapies • Anti-TNF- α therapy • Other therapies

  4. Long-term evolution of Disease Behaviour in CD 100 90 80 70 Penetrating 60 50 CumulativeProbability(%) 40 Inflammatory 30 Stricturing 20 10 0 0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240 Months Patients at risk: 95 2002 552 229 37 N = Cosnes J et al. Inflamm Bowel Dis. 2002;8:244.

  5. Cumulative incidence of fistula Cumulative incidence of perianal fistula is 23-38%. Schwartz DA et a, Gastroenterology.2002;122;875

  6. The risk of developing perianal fistulas increases when the disease involves the distal bowel Hellers G et at. Gut 1980; 21: 525–7.

  7. Distribution of fistulae From patients in the Olmstead County, Minnesota. Crohn's disease cohort, from 1970 to 1995 Schwartz DA et al. Gastroenterology 2002; 122: 875–80.

  8. The natural history of fistulizing Crohn's disease population based study Schwartz D. Gastroenterology 2000; 118(4): A337

  9. Accurately defining perianal fistulae is a prerequisitefor medical and surgical treatment strategies • The course of the tracts through the anal sphincter structures • Number • Complexity • The presence of abscess. • the presence of stricturing intestinal disease Schwartz DA,et al. Gastroenterology 2001; 121: 1064–72.

  10. Normal Anatomy

  11. Classification of Perianal Fistula Park’s classification A Superficial fistula B Intersphincteric fistula C Transsphincteric fistula D Suprasphincteric fistula E Extrasphincteric fistula Parks AG et al. Br J Surg 1976; 63(1): 1–12.

  12. Simple fistula Superficial Inter-sphincteric low trans-sphincteric One opening NO abscess NO connection to an adjacent structure. Complex fistula Involves more of the anal sphincters High trans-sphincteric or Extra-sphincteric or Supra-sphincteric Multiple openings Associated with: perianal abscess Connects to an adjacent structure, such as the vagina or bladder. Classification proposed by AGA technical review on perianal Crohn's disease AGA medical position statement: perianal Crohn's disease. Gastroenterology 2003; 125(5): 1503–7.

  13. Outcome measures Perianal Disease Activity Index Irvine EJ et al. McMaster IBD Study Group. J Clin Gastroenterol 1995; 20: 27–32.

  14. Outcome measures MRI-based score Van Assche G et al. Am J Gastroenterol 2003; 98(2): 332–9.

  15. The optimal way to define a fistula Combination of two of the following tests: • Magnetic resonance imaging (MRI) of the pelvis • Endoscopic ultrasound (EUS) • Examination under anaesthesia Schwartz DA,et al. Gastroenterology 2001; 121: 1064–72.

  16. Spontaneous healing rate of fistulae in patients with Crohn’s disease • Present DH. N Engl J Med 1980; 302:981–7. • Present DH. N Engl J Med 1999; 340: 1398–405. • Sandborn WJ. Gastroenterology 2003;125: 380–8.

  17. Therapeutic approach

  18. Therapeutic Goals in the Management of Fistulizing Crohns Disease • Control overall disease activity • Induce closure of fistulas • Maintain closure of fistulas • Limit scope of surgical intervention • Improve quality of life

  19. Efficacy of agents evaluated to treat fistulizing Crohn’s disease MP, mercaptopurine; GM-CSF, granulocyte-macrophage colony-stimulating factor

  20. Onset of action of different therapies on fistula closure Infliximab MP/Azathioprine 2 weeks 4 weeks 1 week 10 weeks 12 weeks 24 weeks Cyclosporine & Tacrolimus Antibiotics

  21. Antibiotics

  22. Antibiotics for Perianal Fistulas in CD Metronidazole 20mg/kg/day Open trials Complete healing reported in about 50% of patients receiving Metronidazole, alone or in combination.¹־³ ¹ Bernstein LH et al.Gastroenterology.1980;79;357 ² Schneider MU et al. DIsch Med Wochenschr 1981;106;1126 ³ Jakobvitz et al. Am J Gastroeterol.1984;79;533

  23. Antibiotics for Perianal Fistulas in CD Metronidazole • Symptomatic recurrence in 78% of patients within 4 months of stopping therapy • Side effects of metronidazole include: • Dyspepsia • Metallic taste • A disulfiram-like response to alcohol intake. • Peripheral neuropathy and paresthesias limit the use of this agent for long-term treatment. • Brandt LJ. Gastroenterology 1982; 83: 383–7.

  24. Antibiotics for Perianal fistulas in CD Ciprofloxacin 500 - 1500mg/day 1Turunen U et al. Scand J Gastroenterol 1989; 24 (Suppl. 48): 144. 2 Wolf J et al. Gastroenterology 1990; 98: A212 (abstract).

  25. Antibiotics for Perianal fistulas in CD Ciprofloxacin 1000 - 1500mg/day + Metronidazole 500-1500mg/day Uncontrolled trial Solomon M et al, Can J Gastroenterol 1993; 7: 571–3.

  26. Antibiotics for Perianal fistulas in CD Antibiotics are not the ideal solution to the problem • Side effects • Low rate of fistula closure • Recuurence on D/C Bridge strategy for azathioprine therapy ?

  27. Onset of action of different therapies on fistula closure Infliximab MP/Azathioprine 2 weeks 4 weeks 1 week 10 weeks 12 weeks 24 weeks Cyclosporine & Tacrolimus Antibiotics

  28. Antibiotic and AZA for the treatment of perianal fistulas in Crohn'sdisease. Relapse No AZA (n=19) Response 16% Without AZA Response 54% (n=35) Maintained response AZA (n=14) Response 50% Response 41% With AZA Continued AZA (n=15) Response 47% Maintained response (n=17) After antibiotic Treatment Without antibiotics Week 8 Week20 Week 32 Cipro+/-Flagyl C. Dejaco et al Aliment Pharmacol Thera Volume 18 Issue 11-12 Page 1113 - 2003

  29. Ciprofloxacin 500mg BID combined with Infliximab for Perianal Fistulas in CD 24 Patients Inflx Inflx Inflx West RL et al, Aliment Pharmacol Ther 2004; 20: 1329–36.

  30. MERCAPTOPURINEAND AZATHIOPRINE

  31. A meta-analysis incorporating five randomized,placebo-controlled trials of MP or azathioprinewith fistula response as a secondary outcome 29 Patients 41 patients Response : Either complete healing or decreased discharge from fistulae. Pearson DC et al, A meta-analysis.Ann Intern Med 1995; 123: 132–42.

  32. Predicting clinical response to 6-MP/AZT using a combination of the 6-TGN metabolite level and TPMT activity Higher relaps Higher 6-MMP/6-TGN ratios Lower response Allopurinol * 6-Thioguanine (6-TGN) A marker for drug efficacy 6-MP/AZT 5 ASA 6-methylmercaptopurine (6-MMP) Associated with hepatotoxicity Thiopurine methyltransferase(TPMT) * Witte TN. Am J Gastroenterol. 2006;101:S432-433. [Abstract 1105]

  33. Improved efficacy of MP or azathioprine by tailoring of doses using MP metabolites Erethrocyte 6-thioguanine; 6-TGN) levels (>250 pmol/8 ×10 red blood cells). Could optimize clinical response 8 Cuffari C, et al. Gut 2001; 48: 642–6.

  34. Adverse events while on MP or azathioprine • Pancreatitis (3%) • Allergic reactions • Infections • Leucopoenia • Drug-induced hepatitis • Small increase in risk of lymphoma

  35. Ciclosporin and Tacrolimus

  36. Ciclosporin may have a role in the acute management of fistulizing Crohn’s disease. 10 case series 64 patients • Initial response rate 83% • Sustained response 38%

  37. Ciclosporin may have a role in the acute management of fistulizing Crohn’s disease. • Improvement typically within 1 week • Relapse rate is high on D/C • ??Rescue therapy to induce fistula closure • ??Bridge therapy to maintenance treatment with other slower acting immune modifier agents, such as azathioprine or mercaptopurine.

  38. Side effects of Ciclosporin include: • Hypertension • Headache • Hirsutism • Hypertrichosis • Hypertriglyceridaemia • Nausea • Gingival hyperplasia • Tremor • Paresthesia • nephropathy • Immunosuppression.

  39. Tacrolimus (FK-506) in the treatment of fistulizing Crohn’s disease Randomized double-blind placebo-controlled multicentre trial 43 patients P= 0.004 Therapy for 10 weeks Abdominal fistulae failed to close Fistula improvement defined as: closure of ‡50% of fistulae that were draining at baseline and maintenance of closure for ‡4 weeks) Sandborn WJ et al, Gastroenterology 2003; 125: 380–8.

  40. Tacrolimus (FK-506) in the treatment of fistulizingCrohn’s disease Subanalysis of the same study: 15 patients treated with infliximab in the past • 47% improved on tacrolimus. • ?? alternative therapy in patients • Intolerant to infliximab • Refractory to infliximab Sandborn WJ et al, Gastroenterology 2003; 125: 380–8.

  41. Tacrolimus should likely remain an agent of last resort. Known side effects of Tacrolimus: • Headache • Insomnia • Paresthesia • Tremor • Increased serum creatinine

  42. The Perianal Disease Activity Index • The PDAI score is a simple 5-point index • Scores range from 0 to 20 • Higher scores indicate more severe disease activity. • The five elements are • The presence or absence of discharge • Pain or restriction of daily living activities • Restriction of sexual activity • The type of perianal disease • The degree of induration Irvine EJ et al. McMaster IBD Study Group. J Clin Gastroenterol 1995; 20: 27–32.

  43. Methotrexate

  44. Has been shown to induce and maintain remission in patients with Crohn’s disease But its role in treating Crohn’s disease fistulae has not been adequately studied. Methotrexate A retrospective review of a single centre’s experience Soon SY. Eur J GastroenterolHepatol 2004; 16: 21–6.

  45. Fistula Response to Methotrexate in Crohn's Disease: A Case Series A retrospective chart review of 16 patients with fistulizing crohn’s diseas 1989 - 1997 U. Mahadevan Aliment Pharmacol Ther 18(10):1003-1008, 2003.

  46. Adverse events of Methotrexate • Intestinal distress and alopecia are dose related and indicators of unacceptable toxicity • Idiosyncratic allergic-type reactions • Rash • Pneumonitis in 3-11% • Liver toxicity • Abnormal serum ALT (30%) • Histological abnormalities • 95% mild • 2% hepatic fibrosis. • Contraindications: • Other risk factors for liver disease • Men and women attempting conception

  47. Infliximab (Anti-TNF-α )

  48. Infliximab for fistulizing CD Response 94 patients P=0.002 Treatment period W0 W2 W6 W10 W14 W18 Primary end point : at least 50% reduction from baseline of the number of draining fistulae on at least two consecutive assessments (performed at times of infusion and at 10, 14 and 18 weeks). Present DH. N Engl J Med 1999; 340: 1398–405.

  49. Infliximab for fistulizing CD Complete closure 94 patients P=o.oo1 Treatment period W0 W2 W6 W10 W14 W18 A complete response (defined as the absence of any draining fistulae at two consecutive visits) Present DH. N Engl J Med 1999; 340: 1398–405.

  50. Infliximab for fistulizing CD (n=21) (n=18) (n=39) Present DH et al. N Engl J Med. 1999;340;1398

More Related