Kim L. Isaacs, MD, PhD, said at the annual meeting of the American College of Gastroenterology.
Bruce Jancin/MDedge News
Dr. Kim L. Isaacs
First, it’s essential to establish that a patient truly falls into the mild disease category. And second, during that initial evaluation it’s important to look for the features that signal a high risk of subsequent disease progression.
“Patients with risk factors for disease progression should not be treated as mild Crohn’s disease. These are people that we need to treat perhaps more aggressively up front,” said Dr. Isaacs, professor of medicine and codirector of the Multidisciplinary Center for IBD Research and Treatment at the University of North Carolina, Chapel Hill.
Management of patients with severe Crohn’s disease can be challenging, but Dr. Isaacs finds patients with mild disease flat out “terrifying.”
“The reason I find this situation terrifying is we want to prevent the surgery, the progression from inflammatory disease to more stricturing and penetrating disease. And how can I know that my patient a year from now is not going to be very, very ill and I’ve lost my window to use some of our more potent therapies?” she explained.
Mild Crohn’s disease is characterized clinically by less than 10% weight loss; no fever, tachycardia, or other symptoms of systemic disease; lack of abdominal tenderness; and no signs or symptoms of obstruction. When reading the literature, mild disease is defined by a Crohn’s Disease Activity Index score of 150-220. However, nobody uses that metric outside of research studies; it’s just too cumbersome. More useful in routine clinical practice is the Harvey-Bradshaw Index, where a score of 5-7 indicates mild disease.
Many patients with mild Crohn’s disease will not progress over time. In a recent prospective 29-center European study, just 14% of patients progressed from mild to stricturing and/or penetrating disease within 5 years after diagnosis (Gut. 2018 Jan 23. doi: 10.1136/gutjnl-2017-315568).
Who is likely to progress
Risk factors for disease progression include patients with ileocolonic or perianal disease, smokers, those with inflammatory arthritis or other associated immune-mediated disease, and patients who require corticosteroids in order to maintain remission.
On the other hand, patients with mild Crohn’s disease at low risk for progression have no or only mild symptoms, a limited distribution of bowel inflammation, normal or merely slightly elevated C-reactive protein and/or fecal calprotectin levels, no or only superficial bowel ulceration on colonoscopy, and were diagnosed with inflammatory bowel disease after age 30.
Treatment options
“Our goal in a patient we think is low risk is symptomatic management while avoiding high therapeutic risks in someone we don’t think is going to be progressing,” according to the gastroenterologist.
In patients with mild disease who have symptoms in the ileum or right colon, a good strategy is to induce remission using controlled ileal-release budesonide at 9 mg/day, then follow up with colonoscopy 6-12 months later. The high-dose budesonide regimen has been shown in multiple studies to be more effective than placebo at inducing remission. It’s less effective than conventional oral corticosteroids, but it also causes fewer steroid-related side effects. In fact, the evidence shows that the side effect profile of controlled-release budesonide is no different from that of placebo.
In low-risk, mildly symptomatic patients with diffuse Crohn’s colitis, Dr. Isaacs recommends initial treatment with prednisone and/or sulfasalazine or 5-aminosalicylates. The 5-aminosalicylates aren’t part of most practice guidelines because of conflicting study results. However, a meta-analysis of 22 randomized controlled trials has shown that high-dose mesalamine was 2.29-fold more effective than placebo at inducing remission and is a good option for patients who would rather avoid corticosteroids (Inflamm Bowel Dis. 2017 Mar;23(3):461-72). Prednisone should be tapered after achieving clinical remission. Inability to stop steroids within 6 months after entering remission warrants a switch to maintenance therapy with a biologic or immunomodulatory agent.