Existing and Emerging Therapies in IBD

Data-driven decision making, decision support tools, and new and emerging therapeutic agents represent major advances in providing personalized care for patients with inflammatory bowel disease (IBD), Parambir Dulai, MD told the attendees at the  Advances in Inflammatory Bowel Disease (AIBD) 2022 virtual regional meeting March 5.

Dr Dulai is a gastroenterologist at Northwestern Medicine Digestive Health Center in Chicago, Illinois.

Dr Dulai explained that IL-23 inhibitors that block the p19 subunit are more controlled than those that block the p40 subunit, which enables less off-target immunosuppression. He highlighted 4 IL-23p19 inhibitors that are currently in phase 3 trials: risankizumab, guselkumab, brazikumab, and mirikizumab.

All of these emerging IL-23 inhibitors have been shown to have a clinical remission rate of at least 25%-28% at week 8 in Crohn disease (CD). Guselkumab had the highest clinical remission rate, with 54%. Additionally, for patients with ulcerative colitis (UC), mirikizumab has shown clinical remission and response rates that are comparable to ustekinumab, an IL-23p40 inhibitor, at week 12.

Dr Dulai considered all 4 of these emerging therapies to be promising and potentially as effective as ustekinumab for treating both UC and CD.

When considering currently available therapies, Dr Dulai highlighted 2 studies comparing ustekinumab to other available treatments for patients with CD. The SEAVUE trial compared ustekinumab to the tumor necrosis factor (TNF)-inhibitor adalimumab. Both the clinical remission rates and the steroid-free clinical remission rates of ustekinumab were higher than those of placebo and were comparable to those of adalimumab. At all time points during the trial, both therapies showed similar rates of clinical remission and endoscopic remission. However, adalimumab was found to have a higher rate of injection site reactions and discontinuation than ustekinumab.

Overall, ustekinumab and adalimumab had comparable efficacy in biologic-naïve patients with early, moderately active CD. These trial results suggest that ustekinumab could be a reasonable first-line option.

In a post hoc analysis comparing ustekinumab to infliximab for patients with CD, researchers found that, at week 6, the ustekinumab cohort had achieved comparable clinical remission, clinical response, and fecal calprotectin rates to infliximab. Therefore, Dr Dulai summarized, ustekinumab and infliximab showed similar efficacy in biologic-naïve patients with CD.

Dr Dulai also highlighted decision support tools that exist for the use of ustekinumab and vedolizumab. These tools can help providers by stratifying a patient into low, intermediate, or high probability of response to either drug. A recent study found that these decision tools do allow for personalized identification of response patterns and are highly drug specific, meaning the vedolizumab decision support tool successfully stratified the patient probability of response for vedolizumab, but was unable to accurately predict the probability of response for ustekinumab. The same was found for the ustekinumab decision support tool — it accurately predicted the probability of response for ustekinumab, but not for vedolizumab. These tools are free to access for providers.

Dr Dulai reviewed the recent safety update regarding the JAK inhibitor tofacitinib. While the FDA label has been updated to include a warning for infection, heart disease, blood clot, cancer and death, Dr Dulai stated that the context of these warning should be taken into consideration. The warning was based on a postmarketing study of patients 50 years of age, with rheumatoid arthritis and at least 1 risk factor for cardiovascular event. Dr Dulai pointed out that the recently completely UC studies involving tofacitinib 7 years of follow-up have observed over 2,440 patient years of exposure and have found a low rate of observed deaths, serious infections, major cardiovascular events, or malignancies.

Dr Dulai concluded, “Although the labeling change guides practice, it’s important to recognize the differences in population for who we treat and where these labeling changes were made.”

—Allison Casey

Reference:
Dulai P. What’s new with our dld friends. Presented at: Advances in Inflammatory Bowel Disease 2022 Regional Meeting; March 5, 2022; Virtual.