The American College of Gastroenterology has released new guidelines on the diagnosis and treatment of ulcerative colitis (UC), an idiopathic inflammatory disorder that is increasing in incidence throughout the world.
Since the college last published guidelines a decade ago, management has become considerably more complex, with new therapies and techniques, and today, “the optimal goal of management is a sustained and durable period of steroid-free remission, accompanied by appropriate psychosocial support, normal health-related quality of life, prevention of morbidity including hospitalization and surgery, and prevention of cancer,” wrote David T. Rubin, MD, of the University of Chicago, and colleagues, in the American Journal of Gastroenterology.
For diagnosis, the guideline authors stated that UC should be considered for patients with rectal bleeding and urgency, and that infectious causes — especially Clostridioides difficile — should be promptly ruled out. The extent of disease should also be assessed, which can range from limited proctitis to extensive disease beyond the splenic flexure. This requires lower gastrointestinal endoscopy and histologic confirmation.
They proposed a new classification system for disease severity, stratified as mild, moderate-severe, and fulminant. Mild disease is defined as fewer than four stools per day, intermittent bleeding, Mayo endoscopy subscore of 1, elevated C-reactive protein (CRP), normal hemoglobin, and fecal calprotectin (FC) of 150 to 200 µg/g. Moderate to severe disease is characterized by more than six stools per day, frequent blood in stool, elevated CRP, erythrocyte sedimentation rate (ESR) above 30 mm/hour, hemoglobin less than 75% of normal, and Mayo scores of 2 or 3. Disease is classified as fulminant with more than ten stools per day, FC above 150 to 200, ESR above 30, Mayo subscore of 3, and transfusions being needed.
The authors then presented a series of goals for UC management, focusing on induction and remission, symptom control, normalization of bowel frequency, and histologic remission. Because of the chronic nature of UC, therapeutic decisions must include the prevention of treatment-related toxicity and should address potentially coexistent depression and anxiety, which are common among these patients.
Induction treatment of mildly active UC can begin with rectal 5-aminosalicylate therapies, and in patients who fail to reach remission, oral steroids, preferably budesonide, which has a high first-pass metabolism and few adverse effects. Response to induction therapy should be assessed within 6 weeks.
Further study is needed for additional therapies such as probiotics and fecal transplantation, which have shown promise in early investigations.
For induction therapy of moderately to severely active disease, oral corticosteroids are recommended, but monotherapy with methotrexate or thiopurines is not suitable. The anti-tumor necrosis factor (TNF) agents infliximab (Remicade), adalimumab (Humira), and golimumab (Simponi) also are recommended for induction of remission, as are the newer agents vedolizumab (Entyvio) and tofacitinib (Xeljanz). Vedolizumab is an anti-integrin agent that targets the gut mucosal immune system, while tofacitinib is an oral small molecule that targets the Janus kinase enzyme.
A strategy that has been emerging for choosing among the various agents for induction therapy has been the use of more organ-selective treatments before systemic therapies. “In some patient populations, it is reasonable to consider the use of the gut-selective anti-integrin therapy vedolizumab before the use of systemically acting anti-TNF therapies or small molecules such as Janus kinase inhibitors,” Rubin and colleagues advised.
However, for patients who have extraintestinal disease manifestations, the more broadly acting systemic agents could be a preferable approach, they noted.
Once remission has been established, a maintenance strategy should be determined, with the authors emphasizing that systemic corticosteroids should not be used. Maintenance can continue with the anti-TNF agents, vedolizumab, or tofacitinib in patients who responded to induction therapy with these agents.
The next section of the guideline focuses on the care of patients hospitalized with acute, severe UC. These patients should have stool testing to rule out C. diff infection and undergo flexible sigmoidoscopy preferably within 24 hours of admission to assess severity and to test for cytomegalovirus infection.
Treatment should include methylprednisolone or hydrocortisone, and for patients who don’t respond to intravenous corticosteroids in 3 to 5 days, rescue therapy with infliximab or cyclosporine should be given and surgical consultation sought. Surgery is indicated for serious complications including toxic megacolon, perforation, or severe hemorrhage.
The final section addresses colorectal cancer prevention, with screening to begin 8 years after UC diagnosis; recent data suggest that malignant changes can occur early. Colonoscopies should be repeated at 1 to 3-year intervals depending on risk factors such as age, disease duration, and extent of inflammation. Typical lesions in colorectal cancer associated with UC are flat and spreading, whereas discrete and adenoma-like lesions have a lower likelihood of being cancerous in the setting of UC.
“A critical component to a cancer prevention strategy focused on dysplasia detection is accurate histopathologic diagnosis, and several analyses have emphasized the importance of pathologists with expertise reviewing suspected UC-associated neoplasia,” the authors wrote.
Finally, in patients who develop dysplasia, “the evolution of technology has resulted in more directly visualized approaches, removal of endoscopically discrete lesions, and in select patients, active surveillance rather than proctocolectomy,” they concluded.
The authors reported financial relationships with AbbVie, AbGenomics, Allergan, Ferring, Genentech/Roche, Janssen, Merck, Medtronic, Napo Pharmaceuticals, Pfizer, Shire, Takeda, Target Pharma Solutions, Amgen, Celgene, Eli Lilly, Sandoz, Gilead, Prometeus, Sebela, UCB, and Theravance. Support was also provided by the National Institutes of Health and the Crohn’s and Colitis Foundation.