Aug. 17, 2021

Esophageal Crohn's disease (ECD) is a rare, aggressive form of inflammatory bowel disease (IBD). Patients with ECD often present with inflammation, stricture or fistulas of the esophagus, along with small or large bowel disease.

A variety of biologic therapies are among the options available for treatment of ECD and other forms of IBD. These include tumor necrosis factor-alpha (TNFα) inhibitors (certolizumab, infliximab, adalimumab), anti-integrin agents (vedolizumab, natalizumab), and interleukin-12 and interleukin-23 (IL-12 and IL-23) inhibitors (ustekinumab). While the use of these drugs to treat patients with IBD in the lower gastrointestinal tract and patients with Crohn's disease (CD) is well documented, data related to the effectiveness of these treatments in patients with ECD is scarce.

To address this knowledge gap, a group of Mayo Clinic researchers conducted a retrospective review of patients with ECD receiving biologic therapy. The results of that review were published in Inflammatory Bowel Diseases in 2021. According to corresponding author Laura E. Raffals, M.D., a gastroenterologist at Mayo Clinic in Rochester, Minnesota, the Mayo Clinic research team searched for and analyzed outcome data on patients with ECD who received biologic therapy. Specifically, the researchers examined treatment response and optimal management of biologics, and whether the length of time from ECD diagnosis to initiation of biologic therapy impacts outcomes.

The researchers identified 126 patients who received biologic treatment for ECD after diagnosis between January 1998 and September 2018. They examined and recorded each patient's previous medications, overall course of biologic treatment and primary outcomes. The primary outcomes included clinical and endoscopic response to treatment (defined as improvements in esophageal symptoms or endoscopic findings noted after diagnosis), and clinical and endoscopic remission (defined as complete resolution of symptoms and baseline endoscopic findings).

Results and conclusions

Overall, Dr. Raffals and co-authors note that the data examined yielded some useful information about the clinical features and outcomes for this rare diagnosis.

"Patients with esophageal Crohn's disease appear to have more-disabling disease compared with those without esophageal involvement," says Dr. Raffals.

While randomized controlled trials have demonstrated the effectiveness of ustekinumab (an anti-IL-12 and IL-23 agent) in treating moderate to severe intestinal CD, patients in this study who underwent treatment with this agent had worse clinical and endoscopic response when compared with patients who did not receive this therapy.

• Treatment with TNFα agents, when compared with other biologics, was associated with greater improvement in clinical response (96.8% versus 71.4%; P = 0.02) and endoscopic response (94.7% versus 40.0%; P < 0.01) and in clinical remission (64.5% versus 14.2%; P = 0.01) but not endoscopic remission (63.2% versus 20%; P = 0.85).
• Treatment with anti-IL-12 and IL-23 biologics, when compared with other biologic therapy, was associated with poorer clinical response (70% versus 100%; P < 0.01) and endoscopic response (57.1% versus 94.1%; P = 0.03).

"Our findings suggest that patients with ECD who received an TNFα therapy as a first line treatment have better clinical and endoscopic outcomes when compared with other second or third line biologic therapies," explains Dr. Raffals.

The researchers also documented an important finding related to treatment timing. "We observed that earlier treatment was not significantly associated with improved endoscopic or clinical outcomes in ECD," explains Dr. Raffals.

The team acknowledges that the study's limitations and inherent biases include the relatively small sample size and its retrospective design. Additionally, the authors note that patients who received second line or third line biologic therapy may have already failed to respond to anti-TNFα therapy earlier in their disease course.

"A prospective study evaluating the effectiveness of the different biologic therapies is needed to address these limitations," says Dr. Raffals.

For more information

Lui J, et al. The use of biologics for the treatment of esophageal Crohn Disease. Inflammatory Bowel Diseases. In press.