AGA Institute Guidelines for the Identification, Assessment and Initial Medical Treatment in Crohn’s Disease

CLINICAL CARE PATHWAY


Identify as low-risk patient

Identify as moderate/high-risk patient

Assess inflammatory status

Assess symptoms/signs

  • Fever
  • Abdominal pain
  • GI bleeding
  • Localized tenderness
  • Weight loss
  • Joint pain
  • Cutaneous signs

Perform clinical lab testing

  • CBC
  • CRP
  • CMP
  • Fecal calprotectin
  • ESR

Select imaging modalities (if indicated)


* Selection depends on local expertise and experience with imaging modalities. Magnetic resonance enterography is preferred due to the reduction in ionizing radiation, particularly for younger patients. If patient is less than 50 years of age, we suggest using magnetic resonance enterography

Perform endoscopy

‡ Consideration could be given as to whether to make treatment decisions based on inflammatory markers versus confirming with colonoscopy. This may depend on whether there was historically good correlation between the biomarker selected and colonoscopy in the specific patient.

Identify symptoms without inflammatory markers

Identify symptoms with inflammatory markers

Perform CT-enterography OR magnetic resonance enterography(*,1,2,3)

Infections

C. difficile, CMV, food poisoning(4,5,6)

Stricture/remodeling

Abnormal imaging (bowel dilation)
Obstructive symptoms
Weight loss(7,8,9)

Symptoms related to prior surgery

Bile acid diarrhea
Bacterial overgrowth
Steatorrhea/fat malabsorption(10)

Adverse reaction to medical therapy

Recent introduction of new agent; drug holiday(11)

Abdominal abscess or fistula

Pain, fistula drainage, fever

Perianal abscess or fistula

Pain, fistula drainage, fever

Assess current and prior disease burden

Identify patient as low risk(12)

  • Age at initial diagnosis > 30 years
  • Limited anatomic involvement
  • No perianal and/or severe rectal disease
  • Superficial ulcers
  • No prior surgical resection
  • No stricturing and/or penetrating behavior

Identify patient as moderate/high risk(12)

  • Age at initial diagnosis < 30 years
  • Extensive anatomic involvement
  • Perianal and/or severe rectal disease
  • Deep ulcers
  • Prior surgical resection
  • Stricturing and/or penetrating behavior

Perform initial treatment

Low-risk patient

Mod/high-risk patient§

Ileum and/or proximal colon — none to minimal systemic symptoms

Options:

  • Budesonide 9 mg per day with or without AZA
  • Tapering course of prednisone with or without AZA

Diffuse or left colon — none to minimal systemic symptoms

Options:

  • Tapering course of prednisone with or without AZA

Moderately severe Crohn’s

Options:

  • Use anti-TNF monotherapy over no therapy or thiopurine monotherapy(13)
  • Use anti-TNF + thiopurine over thiopurine monotherapy or anti-TNF monotherapy(13)
  • Use methotrexate for patients who do not tolerate purine analog in combination with anti-TNF


§ Combination therapy with immunosuppressant and anti-TNF biologic offers improved efficacy and durability compared with anti-TNF monotherapy and should be considered for mod/high-risk patients requiring 2nd or 3rd biologic.

Perform treatment for patient in remission

Low-risk patient

Mod/high-risk patient#

Options:(14)

  • Stop therapy and observe (high chance of relapse over 1 year)
  • Budesonide 6 mg/day (median time to relapse prolonged by approximately 114 days, but no difference in remission rates versus placebo at 1 year)*
  • Immunosuppressive therapy (AZA, 6MP and MTX have been shown to be effective for maintaining steroid-induced remissions with prednisone or prednisolone, but are associated with rare risk of infection and lymphoma)

* Consider bone mineral density monitoring

Steroid induced remission(13)

Options:

  • Use immunomodulator (thiopurine or MTX) over no immunomodulator
  • Use anti-TNF +/- thiopurine over no anti-TNF

Anti-TNF or anti-TNF + thiopurine induced remission(13)

  • Use anti-TNF +/- thiopurine over no anti-TNF

Does not remain in remission for 6 months

Remains in remission for 6 months

# Combination therapy with immunosuppressant and anti-TNF biologic offers improved efficacy and durability compared with anti-TNF monotherapy and should be considered for mod/high-risk patients requiring 2nd or 3rd biologic.

Define resolution of inflammation and ulcers

Re-assess inflammatory markers every 3 months

Perform treatment for patient not in remission

Low-risk patient

Mod/high-risk patient

Options:

  • Immunosuppressive
  • Assess drug levels
  • Consider anti-TNF therapy(13)

Options:(13)

  • Use anti-TNF monotherapy over no therapy or thiopurine monotherapy
  • Use anti-TNF + thiopurine over thiopurine monotherapy or anti-TNF monotherapy

Failure to respond

Positive response

Low or undetectable drug concentration and low or undetectable anti-drug

Low or undetectable drug concentration and high anti-drug antibody

Therapeutic drug concentration and low or undetectable anti-drug antibody

Increase drug dose

Switch within drug class

Assess inflammation

Inflammation present

Inflammation not present

Switch to another drug class

Continue drug at current dose and look for other causes

Download the PDF

Sandborn WJ. Crohn's Disease Evaluation and Treatment: Clinical Decision Tool. Gastroenterology 2014;147:702-705.

Authors:

William Sandborn, MD, AGAF, David Binion, MD, Kimberly Persley, MD, Ashish Atreja, MD, MPH, Lawrence Kosinski, MD, MBA, AGAF

References:
  1. Bruining DH, Siddiki HA, Fletcher JG, Sandborn WJ, Fidler JL, Huprich JE, Mandrekar JN, Harmsen WS, Evans PE, Faubion WA, Hanson KA, Ingle SB, Pardi DS, Schroeder KW, Tremaine WJ, Loftus EV. Benefit of computed tomography enterography in Crohn’s disease: effects on patient management and physician level of confidence. Inflammatory Bowel Diseases 2012;18:219-225.
  2. Solem CA, Loftus EV, Fletcher JG, Baron TH, Gostout CG, Petersen BT, Tremaine WJ, Egan LJ, Faubion WA, Schroeder KW, Pardi DS, Hanson KA, Jewell DA, Barlow JM, Fidler JL, Huprich JE, Johnson CD, Harmsen WS, Zinsmeister AR, Sandborn WJ. Small-bowel imaging in Crohn’s disease: a prospective, blinded, 4-way comparision trial. Gastrointestinal Endoscopy 2008;68:255-266. 3
  3. Higgins PD, Caoili E, Zimmermann M, Bhuket TP, Sonda LP, Manoogian B, Platt JF, Zimmermann EM. Computed tomographic enterography adds information to clinical management in small bowel Crohn’s disease. Inflammatory Bowel Diseases 2007;13:262-268.
  4. Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, Skaros S, Weber LR, Komorowski RA, Knox JF, Emmons J, Bajaj JS, Binion DG. Impact of Clostridium difficile on inflammatory bowel disease. Clinical Gastroenterology and Hepatology 2007;5(3):345-51.
  5. Lawlor G, Moss AC. Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflammatory Bowel Diseases 2010;16(9):1620-7.
  6. Meyer AM, Ramzan NN, Loftus EV Jr, Heigh RI, Leighton JA. The diagnostic yield of stool pathogen studies during relapses of inflammatory bowel disease. Journal of Clinical Gastroenterology 2004;38(9):772-5.
  7. Swoger JM, Binion DG. Supportive therapy in IBD: what additional diagnoses and conditions must be treated? Digestive Diseases 2010;28(3):452- 62.
  8. Otterson MF, Lundeen SJ, Spinelli KS, Sudakoff GS, Telford GL, Hatoum OA, Saeian K, Yun H, Binion DG. Radiographic underestimation of small bowel stricturing Crohn’s disease: a comparison with surgical findings. Surgery 2004;136(4):854-60.
  9. Wold PB, Fletcher JG, Johnson CD, Sandborn WJ. Assessment of small bowel Crohn disease: noninvasive peroral CT enterography compared with other imaging methods and endoscopy--feasibility study. Radiology 2003;229(1):275-81.
  10. Hofmann AF, Poley JR. Role of bile acid malabsorption in pathogenesis of diarrhea and steatorrhea in patients with ileal resection. I. Response to cholestyramine or replacement of dietary long chain triglyceride by medium chain triglyceride. Gastroenterology 1972;62(5):918-34.
  11. Bajaj JS, Saeian K, Varma RR, Franco J, Knox JF, Podoll J, Emmons J, Levy M, Binion DG. Increased rates of early adverse reaction to azathioprine in patients with Crohn’s disease compared to autoimmune hepatitis: a tertiary referral center experience. American Journal of Gastroenterology 2005;100(5):1121-5.
  12. Ordás I, Feagan B, Sandborn WJ. Early use of immunosuppressives or TNF antagonists for the treatment of Crohn’s disease: time for a change. Gut 2011;60:1754-1763.
  13. Terdiman JP, Gruss CB, Heidelbaugh JJ, Sultan S, Falck-Ytter YT. American Gastroenterological Association Institute Guideline on the use of Thiopurines, Methotrexate, and Anti-TNF- α Biologic Drugs for the Induction and Maintenance of Remission in Inflammatory Crohn’s Disease. Gastroenterology 2013;145:1459-1463.
  14. Sandborn WJ, Feagan BG, Lichtenstein GR. Medical management of mild to moderate Crohn’s disease: evidence-based treatment algorithms for induction and maintenance of remission. Alimentary Pharmacology & Therapeutics 2007;26:987-1003.
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