Treatment

Design and created by Guideline Central in participation with the American Gastroenterological Association.

Moderate to Severe Luminal and Fistulizing Crohn’s Disease

American Gastroenterological Association

Publication Date: July 21, 2021

Key Points

Crohn’s disease (CD) is a chronic inflammatory bowel disease with substantial morbidity when not adequately controlled.
- Historically, approximately 20% of patients with CD were hospitalized every year, and the risk of surgery within 1 year of diagnosis was 24%, 36% by 5 years, and 47% by 10 years.
- In recent years, outcomes have improved, likely because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer.
The International Organization for the Study of Inflammatory Bowel Diseases characterizes severe disease as having a high risk for adverse disease-related complications, including surgery, hospitalization, and disability, based on a combination of structural damage, inflammatory burden, and impact of quality of life.
- Contributors to severe disease include large or deep mucosal lesions on endoscopy or imaging, presence of fistula and/or perianal abscess, presence of strictures, prior intestinal resections, particularly of segments >40 cm, presence of a stoma, extensive disease (ileal involvement >40 cm, or pancolitis), anemia, elevated C-reactive protein, and low albumin.
- With respect to symptoms, patients with severe disease may have at least 10 loose stools per day, daily abdominal pain, presence of anorectal symptoms (eg, anorectal pain, bowel urgency, incontinence, discharge, and tenesmus), systemic corticosteroid use within the prior year, lack of symptomatic improvement despite prior exposure to biologics and/or immunosuppressive agents, or significant impact of the disease on activities of daily living.
The Crohn’s Disease Activity Index standardized disease assessment score categorizes severity of disease as: remission <150, mild to moderate as 150–220, moderate to severe as 220–450 and severe >450.
- For this guideline, moderate to severe disease was considered a Crohn’s Disease Activity Index score of 220 or higher.
There are a number of different drug classes available for the management of moderate to severe CD, including:
- Tumor necrosis factor (TNF)–α antagonists (ie, infliximab, adalimumab, certolizumab pegol), anti-integrin agents (natalizumab, vedolizumab), interleukin 12/23 antagonist (ustekinumab), immunomodulators (thiopurines, methotrexate), and corticosteroids (prednisone, budesonide).
In general, most drugs, with the exception of corticosteroids, that are initiated for induction of remission are continued as maintenance therapy.

GRADE Strength of Recommendations and Implications

Grade	Quality of Evidence
High	We are very confident that the true effect lies close to the estimate of the effect.
Moderate	We are moderately confident that the true effect lies close to that of the estimate of the effect. There is a possibility that it is substantially different.
Low	Our confidence that the true effect lies close to that of the estimate of the effect is low. The true effect may be substantially different from the estimate of the effect.
Very low	We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect.
Evidence / Knowledge Gap	Available evidence insufficient to determine true effect.

Grade	Strength of Recommendation
Strong “AGA recommends...”	For the Patient	For the Clinician	For policy makers
Strong “AGA recommends...”	Most individuals in this situation would want the recommended course and only a small proportion would not.	Most individuals should receive the intervention. Formal decision aids are not likely to be needed to help individuals make decisions consistent with their values and preferences.	The recommendation can be adapted as policy or performance measure in most situations.
Conditional (weak) “AGA suggests...”	The majority of individuals in this situation would want the suggested course, but many would not.	Different choices will be appropriate for individual patients consistent with his or her values and preferences. Use shared decision making. Decision aids may be useful in helping patients make decisions consistent with their individual risks, values, and preferences.	Policy making will require substantial debate and involvement of various stakeholders. Performance measures should assess whether decision making is appropriate.
No recommendation “AGA makes no recommendation...”		The confidence in the effect estimate is so low that any effect estimate is speculative at this time.

Abbreviations

AGA: American Gastroenterological Association

CD: Crohn's disease

GRADE: Grading of Recommendations Assessment, Development, and Evaluation

PML: progressive multifocal leukoencephalopathy

TNF: tumor necrosis factor

Source Citation

Feuerstein JD, Ho EY, Shmidt E, Singh H, Falck-Ytter Y, Sultan S, Terdiman JP; American Gastroenterological Association Institute Clinical Guidelines Committee. AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn's Disease. Gastroenterology. 2021 Jun;160(7):2496-2508. doi: 10.1053/j.gastro.2021.04.022. PMID: 34051983.

Disclaimer

This resource is for informational purposes only, intended as a quick-reference tool based on the cited source guideline(s), and should not be used as a substitute for the independent professional judgment of healthcare providers. Practice guidelines are unable to account for every individual variation among patients or take the place of clinician judgment, and the ultimate decision concerning the propriety of any course of conduct must be made by healthcare providers after consideration of each individual patient situation. Guideline Central does not endorse any specific guideline(s) or guideline recommendations and has not independently verified the accuracy hereof. Any use of this resource or any other Guideline Central resources is strictly voluntary.

Moderate to Severe Luminal and Fistulizing Crohn’s Disease

Key Points

Treatment

Figure 1. Medical Management of Adult Outpatients with Moderate to Severe Luminal Crohn's Disease

Figure 2. Medical Management of Adult Outpatients With Moderate to Severe Fistulizing Crohn's Disease

Figure 3. Therapeutic Drug Targets

Table 1. Drug Therapy for the Management of Moderate to Severe CD

GRADE Strength of Recommendations and Implications

Abbreviations

Source Citation

Disclaimer