C rohn's disease (CD) is a chronic inflammatory bowel disease with substantial morbidity when not adequately controlled. 1 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. 2 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. CD includes multiple different phenotypes. The Montreal Classification categorizes CD as stricturing, penetrating, inflammatory (nonstricturing and nonpenetrating), and perianal disease. [3][4][5] Each of these phenotypes can present with a range in severity from mild to severe disease. 6 This guideline addresses the medical management of moderate to severe luminal and fistulizing CD. 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. 7 Moderate to severe disease can also be defined using the Crohn's Disease Activity Index. This 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. 8 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)-a antagonists (ie, infliximab, adalimumab, certolizumab pegol), anti-integrin agents (natalizumab, vedolizumab), interleukin 12/23 antagonist (ustekinumab), immunomodulators (thiopurines, methotrexate), and corticosteroids (prednisone, budesonide). 1 In general, most drugs, with the exception of corticosteroids, that are initiated for induction of remission are continued as maintenance therapy. Unless otherwise specified, we do not present separate recommendations for induction and maintenance of remission...

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As one of few studies to track the complete course of sequential HCC therapies, the findings of the present study suggest that HCC patients with intermediate-stage (BCLC stage B) disease may benefit from aggressive interventions not currently included in societal guidelines.

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