Practical Implications for Positioning Therapy in Inflammatory Bowel Disease

Comorbidities, symptoms, and patient preference are important elements to consider when positioning a medication for a patient with inflammatory bowel disease (IBD), according to a presentation by Edward Barnes, MD, MPH, at the Advances in Inflammatory Bowel Diseases (AIBD) Regional in Baltimore, Maryland.

“It’s a challenge to think about how to best position therapies,” Barnes, who is an assistant professor of medicine in the Division of Gastroenterology and Hepatology at the University of North Carolina at Chapel Hill School of Medicine, said during his presentation. “But the earlier we position to start treatment, the earlier we can change the long-term outcomes.”

The main medications for use in the management of IBD are vedolizumab for ulcerative colitis (UC) and Crohn disease (CD), and ustekinumab for CD.

“There are more anti-integrin therapies in the pipeline, but vedolizumab is the main one,” Barnes said.

Data from numerous clinical trials that evaluated the safety and efficacy of vedolizumab has shown high rates of clinical remission and mucosal healing compared with placebo among individuals with IBD.

Barnes also acknowledged the importance of findings from the VARSITY clinical trial.

“This was the first head-to-head trial of 2 biologics,” Barnes said. “[It compared] the efficacy and safety of vedolizumab and adalimumab for the treatment of UC.”

In the VARSITY clinical trial, at 52 weeks, more patients who received treatment with vedolizumab achieved clinical remission (31.3% vs 22.5%) and mucosal healing (39.7% vs 27.7%) than those who received treatment with adalimumab.

“These results are important,” Barnes said.

Ustekinumab, a monoclonal antibody against the p40 subunit of interleukin (IL)-12 and IL-23, is approved for use among individuals with moderate to severe CD.

Barnes noted findings from the UNITI-1 and UNITI-2 clinical trials, where individuals who received treatment with intravenous ustekinumab had a significantly higher rate of response than those who received treatment with placebo. Further, findings from the IM-UNITI clinical trial showed that remission could be sustained with subcutaneous maintenance therapy of ustekinumab.

According to Barnes’ presentation, the following trends to keep in mind when positioning medications include:

• In CD, clinical remission has been achieved with use of infliximab or adalimumab.
• Among patients with CD who have prior exposure to an anti-tumor necrosis factor, adalimumab and ustekinumab are efficacious.
• In CD, ustekinumab and infliximab had lowest risk of serious adverse events and infection.
• In UC, the use of infliximab or vedolizumab have led to high rates of clinical remission and mucosal healing.
• In UC, vedolizumab has the lowest risk of serious adverse events and infection.

Proper positioning of medications, as well as the emergence of new mechanisms, can potentially impact overall management of IBD in the future.

“As gastroenterologists, we have to think critically about how we will position therapies,” Barnes said. “Continued emphasis on the appropriate positioning of these and other novel therapies may ultimately lead to improved outcomes among patients with inflammatory bowel disease.”

—Melinda Stevens

Reference:

Barnes E. Use of anti-integrin and anti-IL 12/23 in IBD. Presented at: Advances in Inflammatory Bowel Disease Regionals. September 7, 2019; Baltimore, MD.