ACG Updates Guidance on Crohn’s Disease Management

The American College of Gastroenterology (ACG) has issued updated guidance on the management of Crohn’s disease (CD) that reflects the surge in development of therapeutic options available since 2018, when the last guideline was published.

These newer treatment options include interleukin-23 (IL-23) blockers risankizumab, mirikizumab, and guselkumab; the anti-IL-12/23 agent ustekinumab; the Janus kinase inhibitor upadacitinib; and the anti-integrin vedolizumab.

The intent of the guideline is to suggest “preferable approaches” to CD management established through “interpretation and collation of scientifically valid research, derived from extensive review of published literature,” said the writing group, led by Gary Lichtenstein, MD, director, Inflammatory Bowel Disease Center, Hospital of the University of Pennsylvania, Philadelphia.

When exercising clinical judgment, the authors advise healthcare providers to “incorporate this guideline along with patient’s needs, desires, and their values to care for patients fully and appropriately with CD.”

The guideline is intended to be “flexible, not necessarily indicating the only acceptable approach,” and shared decision-making with the patient is advised, they stressed.

The 40-page guideline was published online earlier this month in American Journal of Gastroenterology, along with a one-page visual highlights summary.

From Diagnosis to Surgery

The incidence of CD has steadily increased over the past several decades, and both the diagnosis and treatment of patients with CD has evolved since 2018.

Table 1 of the guideline outlines all 35 recommendations for management of CD, which span diagnosis, endoscopy, medical management (broken down by mild-to-moderately severe disease with a lower or higher risk for disease progression), fistulizing CD, when to refer to surgery, and postoperative care (according to low and high risk for postoperative recurrence).

Table 2 of the guideline offers 59 “key concepts” covering clinical features, natural history, intestinal malignancy, diagnosis, disease modifiers, and medical and surgery management. 

In making a diagnosis, it’s important to consider clinical presentation as well as endoscopic, radiologic, histologic, and pathologic findings, the authors said.

They advise using fecal calprotectin (cutoff > 50-100 µg/g) to differentiate inflammatory from noninflammatory disease of the colon.

Routine endoscopic surveillance for colorectal cancer in patients with Crohn’s colitis is also recommended. 

Medical Treatment

“Medical treatment of CD is usually categorized into induction and maintenance therapy,” the authors wrote. Treatment regimens are usually chosen with “a goal to achieve clinical and biomarker response within 12 weeks of treatment initiation followed by durable steroid-free control of disease activity including both clinical and endoscopic remission.” However, objective outcomes like endoscopic improvements have only recently been added to clinical trials, they noted.

The authors stressed that early initiation of advanced therapy is “key” for optimal outcomes and that failure of conventional therapy before initiation of advanced therapy is not required.

For mild-to-moderately severe disease (with a lower risk for progression), oral mesalamine is not recommended for induction or maintenance; ileal release budesonide is recommended for induction but not maintenance; and sulfasalazine should be considered only for those with symptomatic mild colonic CD.

For moderate-to-severe CD (with a higher risk for progression), there are 17 recommendations, including:

• Oral corticosteroids are recommended for short-term induction of remission but not maintenance.
• Azathioprine and 6-mercaptopurine are not recommended for induction of remission but are recommended for maintenance of remission, with thiopurine methyltransferase testing done before initiation. However, given the adverse effect profile of thiopurine monotherapy, newer safer agents for maintenance should be considered.
• Methotrexate for maintenance of steroid-free remission is suggested.
• Anti-tumor necrosis factor (TNF) agents (intravenous infliximab; subcutaneous [SC] adalimumab or certolizumab pegol) are recommended for induction and maintenance; SC infliximab for maintenance only; tuberculosis and hepatitis B status should be checked before treatment.
• Vedolizumab, ustekinumab, upadacitinib, guselkumab, mirikizumab, and risankizumab are all options for induction and maintenance. 

For fistulizing CD, infliximab, adalimumab, antibiotics, upadacitinib, vedolizumab or ustekinumab are recommended options for induction of remission.

Referral to Surgery

In terms of when to refer to surgery, patients with an intra-abdominal abscess > 2 cm should be treated with drainage and antibiotics. Patients with symptomatic fibrostenotic strictures or abdominal abscesses should be considered for surgery, the authors advised.

In patients with surgically induced remission, colonoscopy 6-12 months after surgery is recommended to assess for early recurrent CD.

Patients with a low post-op risk of recurrence can be observed. Patients with a high risk of post-op recurrence should consider starting advanced therapy shortly after resection with an anti-TNF agent or vedolizumab. High-risk patients include active smokers, those with penetrating disease and prior CD resections.

The guidance also emphasizes the importance of addressing disease modifiers including use of nonsteroidal anti-inflammatory drugs, cigarette smoking, diet, and management of stress, depression, and anxiety.

This guideline was funded by the ACG. Disclosures for the guideline writing group are listed with the original article.