Treatment Guidelines for Crohn Disease

With the prevalence of inflammatory bowel disease (IBD) increasing in the United States, the demand for the gastroenterology services could threaten to overwhelm clinics, according to David A. Schwartz, MD. The treatment guidelines for managing Crohn disease developed by the American College of Gastroenterology (ACG) can be a valuable resource for gastroenterologists in managing a growing patient population and determining how best to approach treatment decisions.

Dr Schwartz is the director of the McClain Family Directorship in Gastroenterology and of the Inflammatory Bowel Disease Center at Vanderbilt University Medical Center in Brentwood, Tennessee, where he also serves as professor of medicine.

“Important lessons can be learned from the ACG Treatment Guidelines,” Dr Schwartz said, including the need to “fully assess disease severity, location, and disease phenotype in order to risk stratify patients and pick the appropriate therapeutic option.” The guidelines also enumerate the many options available for induction and maintenance of patients with both low- and high-risk Crohn disease, and emphasize that surgery is a reasonable option for patients with refractory Crohn disease or complications.

Lesson 1 is that gastroenterologists should begin by risk-stratifying their patients, Dr Schwartz explained, determining the location, extent, and severity of disease; whether there are extraintestinal manifestations (EIMs); and identifying comorbidities such as strictures, fistula, or infections. He reviewed the indications of mild, moderate, and severe Crohn disease, such as extent of lesions, levels of serum C-reactive protein, previous treatment failures, and weight loss.

Properly assessing disease activity should include a colonoscopy to assess extent and severity of disease; an esophagogastroduodenoscopy (EGD) if any upper gastrointestinal symptoms exist; computed tomography or magnetic resonance imaging to examine the small bowel, if the patient exhibits symptoms of obstruction; and checking inflammatory markers to correlate clinical symptoms with disease activity.

Dr Schwartz noted that a study of 102 patients with active Crohn disease found that patients with severe ulcerations are "very very likely to need a colectomy within 5 years."

Lesson 2 from the guidelines is to assess the options for treating patients with mild to moderate disease activity and low-risk disease, for both induction and maintenance. Sulfasalazine is recommended for colonic disease only, Dr Schwartz noted, adding that mesalamines should not be used to treat Crohn disease  Budesonide controlled ileal release, 9 mg daily, can be used to treat mild to moderate ileal or ileocecal disease as an acute treatment option. Antibiotics such as ciprofloxacin, metronidazole, or antimycobacterial therapy should not used for primary treatment of luminal Crohn disease, he added.

For mild to moderate Crohn disease in patients at low risk, the ACG guidelines state that there is “no role for maintenance treatment” for sulfasalazine, oral mesalamines, and oral budesonide. The ACG stated that no maintenance treatment “may be an option for asymptomatic or mild disease” and that surgery “may be considered for symptomatic short segment disease.” Low-risk patients with mild Crohn disease should be monitored for disease progression or recurrence.

Lesson 3 concerns the therapeutic options for patients at high risk of colectomy due to moderate to severe disease activity, Dr Schwartz said. “Oral steroids should be used only as short-term induction agents for inflammatory Crohn disease,” and it's important to have "an exit strategy to get these patients off steroids." Thiopurines and methotrexate should be reserved only for maintenance, with no role in induction of remission. For patients who are steroid-resistant or refractory to thiopurines or methotrexate, anti-tumor necrosis factor (TNF) agents are appropriate choices. Combination therapy with infliximab is more effective than monotherapy with thiopurines or infliximab for treatment-naïve patients.

Other treatment options include anti-integrin therapy with vedolizumab, with or without an immunomodulator; ustekinumab for patients who have failed steroids, thiopurines, methotrexate, anti-TNFs, or who are anti-TNF naïve; and biosimilars, with the same indications as originator anti-TNFs for de novo induction. Dr Schwartz noted that there is insufficient data to support the “safety and efficacy of switching patients in stable disease maintenance.” He added that cyclosporine, mycophenolate mofetil, and tacrolimus should not be used for induction in these patients.

According to a systematic review with a network meta-analysis, Dr Schwartz stated, the effect size for first-line induction therapy for moderate to severe Crohn disease was strongest for infliximab and adalimumab.

“In general, in order to maintain remission, you should continue the agent used to induce remission,” he said. He reported that the ACCENT, CHARM, and PRECISE2 studies of infliximab, adalimumab, and certolizumab pegol found that net clinical remission at or around 6 months was reported as 22.8%, 23.3%, and 30.7%, respectively. Vedolizumab is effective as maintenance therapy in Crohn disease, and the IM-UNITI study found that ustekinumab sustained clinical remission at 36 to 44 weeks in about 48% to 53% of patients.

Lesson 4 from the ACG guidelines, Dr Schwartz stated, deals with when to refer patients to surgery and how to prevent recurrence postoperatively.

“Surgery is often required to treat enteric complications,” he said, as in the case of resection of a diseased segment of bowel due to an obstruction or fistula. Indications for surgery include hemorrhage, perforation, abscess, dysplasia or cancer, and refractory disease. “Patients with abdominal abscess should have surgical resection,” he stated. The surgical philosophy for Crohn disease is that cure is not possible, but surgery is indicated for nonreversible manifestations, unlike in ulcerative colitis, in which surgery is designed to cure disease and provide protection against the development of cancer.

“In post-op Crohn disease, perioperative risk stratification determines management,” he said. Risk factors include current or recent smoking, penetrating disease, more than 2 previous surgeries, ileocolonic or long-segment disease, preoperative steroid treatment, and perianal disease.

For patients with any of these risk factors, Dr Schwartz said, the ACG guidelines recommend beginning anti-TNF or immunomodulator treatment soon after surgery and performing a colonoscopy at 6 to 12 months and every 3 years after if there is no disease recurrence. If Crohn disease does recur, medications should be increased or switched as indicated.

Patients who have low risk prior to surgery do not require medication initially. A colonoscopy should be performed at 6 months. If there is no disease recurrence, a colonoscopy should be performed every 3 years; if disease recurs, the patient should be treated with an anti-TNF agent or immunomodulator.

Dr Schwartz stated, “IBD is forecasted to increase until a total of 2.2 million Americans will be living with IBD in 2025. This speaks to the burden that we’ll see placed on gastroenterologists, which may overwhelm GI clinics. This will necessitate innovations in health care to meet demand.” Using the ACG guidelines can help increase efficiency and ensure availability of care to patients with Crohn disease.

—Rebecca Mashaw

Reference:

Schwartz, DA. Management of Crohn disease: what do the treatment guidelines tell us? Talk presented at: Advances in Inflammatory Bowel Disease 2020 regional meeting; September 12, 2020; virtual.