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    Management of Crohn’s Disease in Adults (beta)

    Official guideline from the American College of Gastroenterology.

    Evidence
    High quality evidence
    Moderate quality evidence
    Low quality evidence
    Very low quality evidence
    Strength
    Strong recommendation
    Conditional recommendation
    Weak recommendation

    Diagnosis

    Routine Laboratory Investigation
    1. Fecal calprotectin is a helpful test that should be considered to help differentiate the presence of IBD from irritable bowel syndrome (IBS).
    Endoscopy
    1. In patients at particularly high risk for colorectal neoplasia (e.g., personal history of dysplasia, primary sclerosing cholangitis), chromoendoscopy should be used during colonoscopy, as it may increase the diagnostic yield for detection of colorectal dysplasia, especially compared with standard-definition white light endoscopy.
    2. For patients undergoing surveillance colonoscopy there is insufficient evidence to recommend universal chromoendoscopy for IBD colorectal neoplasia surveillance if the endoscopist has access to high-definition white light endoscopy.
    3. Narrow-band imaging should not be used during colorectal neoplasia surveillance examinations for Crohn’s disease.
    4. Endoscopists who are sufficiently trained and comfortable performing chromoendoscopy may be able to forgo obtaining random surveillance biopsies. and rely on targeted biopsies alone.
    Disease Modifiers
    1. Nonsteroidal anti-inflammatory drugs (NSAIDs) may exacerbate disease activity and should be avoided when possible in patients with Crohn’s disease.
    2. Cigarette smoking exacerbates disease activity and accelerates disease recurrence and should be avoided. Active smoking cessation programs should be encouraged.
    3. Usage of antibiotics should not be restricted in Crohn’s disease patients in order to prevent disease flares.
    4. Perceived stress, depression, and anxiety, which are common in IBD, are factors that lead to decreased health-related quality of life in patients with Crohn’s disease, and lead to lower adherence to provider recommendations. Assessment and management of stress, depression, and anxiety should be included as part of the comprehensive care of the Crohn’s disease patient.

    Medical Therapy

    Mild-to-moderately Severe Disease/Low-risk Disease
    1. Sulfasalazine is effective for treating symptoms of colonic Crohn’s disease that is mild to moderately active and can be used as treatment for this patient population.
    2. Oral mesalamine has not consistently been demonstrated to be effective compared with placebo for induction of remission and achieving mucosal healing in patients with active Crohn’s disease and should not be used to treat patients with active Crohn’s disease.
    3. Controlled ileal release budesonide at a dose of 9 mg once daily is effective and should be used for induction of symptomatic remission for patients with mild-to-moderate ileocecal Crohn’s disease.
    4. Metronidazole is not more effective than placebo as therapy for luminal inflammatory Crohn’s disease and should not be used as primary therapy.
    5. Ciprofloxacin has shown similar efficacy to mesalamine in active luminal Crohn’s disease but has not been shown to be more effective than placebo to induce remission in Crohn’s disease and should not be used as therapy for luminal inflammatory Crohn’s disease.
    6. Antimycobacterial therapy has not been shown to be effective for induction or for maintenance of remission or mucosal healing in patients with Crohn’s disease and should not be used as primary therapy.
    7. For patients with low risk of progression, treatment of active symptoms with anti-diarrheals, other non-specific medications, and dietary manipulation, along with careful observation for inadequate symptom relief, worsening inflammation, or disease progression, is acceptable.
    Moderate-to-severe Disease/Moderate-to-high-risk Disease
    1. Oral corticosteroids are effective and can be used for short-term use in alleviating signs and symptoms of moderate to severely active Crohn’s disease.
    2. Conventional corticosteroids do not consistently achieve mucosal healing and should be used sparingly.
    3. Azathioprine (at doses of 1.5–2.5 mg/kg/day) and 6-mercaptopurine (at doses of 0.75–1.5 mg/kg/day) are not more effective than placebo to induce short-term symptomatic remission and should not be used in this manner.
    4. Thiopurines (azathioprine, 6-mercaptopurine) are effective and should be considered for use for steroid sparing in Crohn’s disease.
    5. Azathioprine and 6-mercaptourine are effective therapies and should be considered for treatment of patients with Crohn’s disease for maintenance of remission.
    6. Thiopurine methyltransferase (TPMT) testing should be considered before initial use of azathioprine or 6-mercaptopurine to treat patients with Crohn’s disease.
    7. Methotrexate (up to 25 mg once weekly IM or SC) is effective and should be considered for use in alleviating signs and symptoms in patients with steroid-dependent Crohn’s disease and for maintaining remission.
    8. Anti-TNF agents (infliximab, adalimumab, certolizumab pegol) should be used to treat Crohn’s disease that is resistant to treatment with corticosteroids.
    9. Anti-TNF agents should be given for Crohn’s disease refractory to thiopurines or methotrexate.
    10. Combination therapy of infliximab with immunomodulators (thiopurines) is more effective than treatment with either immunomodulators alone or infliximab alone in patients who are naive to those agents.
    11. For patients with moderately to severely active Crohn’s disease and objective evidence of active disease, anti-integrin therapy (with vedolizumab) with or without an immunomodulator is more effective than placebo and should be considered to be used for induction of symptomatic remission in patients with Crohn’s disease.
    12. Natalizumab is more effective than placebo and should be considered to be used for induction of symptomatic response and remission in patients with active Crohn’s disease.
    13. Natalizumab should be used for maintenance of natalizumab-induced remission of Crohn’s disease only if serum antibody to John Cunningham (JC) virus is negative. Testing for anti-JC virus antibody should be repeated every 6 months and treatment stopped if the result is positive.
    14. Ustekinumab should be given for moderate-to-severe Crohn’s disease patients who failed previous treatment with corticosteroids, thiopurines, methotrexate, or anti-TNF inhibitors or who have had no prior exposure to anti-TNF inhibitors.
    15. Cyclosporine, mycophenolate mofetil, and tacrolimus should not be used for Crohn’s disease.
    Severe/Fulminant Disease
    1. Intravenous corticosteroids should be used to treat severe or fulminant Crohn’s disease.
    2. Anti-TNF agents (infliximab, adalimumab, certolizumab pegol) can be considered to treat severely active Crohn’s disease.
    3. Infliximab may be administered to treat fulminant Crohn’s disease.

    Fistulizing Crohn's Disease

    Perianal/Fistulizing Disease
    1. Infliximab is effective and should be considered in treating perianal fistulas in Crohn’s disease.
    2. Infliximab may be effective and should be considered in treating enterocutaneous and rectovaginal fistulas in Crohn’s disease.
    3. Adalimumab and certolizumab pegol may be effective and should be considered in treating perianal fistulas in Crohn’s disease.
    4. Thiopurines (azathioprine, 6-mercaptopurine) may be effective and should be considered in treating fistulizing Crohn’s disease.
    5. Tacrolimus can be administered for short-term treatment of perianal and cutaneous fistulas in Crohn’s disease.
    6. Antibiotics (imidazoles) may be effective and should be considered in treating simple perianal fistulas.
    7. The addition of antibiotics to infliximab is more effective than infliximab alone and should be considered in treating perianal fistulas.
    8. Drainage of abscesses (surgically or percutaneously) should be undertaken before treatment of fistulizing Crohn’s disease with anti-TNF agents.
    9. Placement of setons increases the efficacy of infliximab and should be considered in treating perianal fistulas.

    Maintenance Therapy of Luminal Crohn's Disease

    Maintenance Therapy of Luminal Crohn's Disease
    1. Once remission is induced with corticosteroids, a thiopurine or methotrexate should be considered.
    2. Patients who are steroid dependent should be started on thiopurines or methotrexate with or without anti-TNF therapy.
    3. Oral 5-aminosalicylic acid has not been demonstrated to be effective for maintenance of medically induced remission in patients with Crohn’s disease, and is not recommended for long-term treatment.
    4. Corticosteroids are not effective for maintenance of medically induced remission in Crohn’s disease and should not be used for long-term treatment.
    5. Budesonide should not be used to maintain remission of Crohn’s disease beyond 4 months.
    6. Anti-TNF therapy, specifically infliximab, adalimumab, and certolizumab pegol, should be used to maintain remission of anti-TNF-induced remission.
    7. Anti-TNF monotherapy is effective at maintaining anti-TNF induced remission, but because of the potential for immunogenicity and loss of response, combination with azathioprine/6-mercaptopurine or methotrexate should be considered.
    8. Vedolizumab should be used for maintenance of remission of vedolizumab-induced remission of Crohn’s disease.
    9. Natalizumab should be considered for maintaining remission of natalizumab-induced remission of Crohn’s disease patients only if John Cunningham (JC) virus is negative.
    10. Ustekinumab should be use for maintenance of remission of ustekinumab-induced response of Crohn’s disease.

    Postoperative Crohn's Disease

    Postoperative Crohn's Disease
    1. All patients who have Crohn’s disease should quit smoking.
    2. Mesalamine is of limited benefit in preventing postoperative Crohn’s disease, but in addition to no treatment is an option for patients with an isolated ileal resection and no risk factors for recurrence.
    3. Imidazole antibiotics (metronidazole and ornidazole) at doses between 1 and 2 g/day can be used after small intestinal resection in Crohn’s disease patients to prevent recurrence.
    4. Thiopurines may be used to prevent clinical and endoscopic recurrence and are more effective than mesalamine or placebo. However, they are not effective at preventing severe endoscopic recurrence.
    5. In high-risk patients, anti-TNF agents should be started within 4 weeks of surgery in order to prevent postoperative Crohn’s disease recurrence.
    6. Although data are lacking in postoperative Crohn’s disease, anti-TNF therapy should be combined with an immunomodulator to decrease immunogenicity and decrease loss of response.
    When to Refer to Surgery
    1. An intra-abdominal abscess should be treated with antibiotics and a drainage procedure, either radiographically or surgically.
    What do the icons mean?  
    Research PaperLichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. Acg clinical guideline: management of crohn’s disease in adults. American Journal of Gastroenterology. 2018;113(4):481-517.