Vedolizumab Promising in Immune-Related GI Events Save

Vedolizumab (Entyvio) was superior to infliximab (Remicade) for treating immune-mediated diarrhea and colitis (IMDC), a researcher reported.

In a retrospective study of patients with cancer, treatment with vedolizumab led to a 13% IMDC recurrence rate versus 28% with infliximab, according to Yinghong Wang, MD, PhD, of the MD Anderson Cancer Center in Houston.

In the cohort, 61 patients received only the adhesion molecule inhibitor, while 71 received only the tumor necrosis factor blocker, and 18 received both. In comparison with the infliximab-only group, patients on vedolizumab alone also showed the following, Wang reported at the American College of Gastroenterology virtual meeting:

• Shorter steroid treatment: 35 vs 50 days (P<0.001)
• One vs two steroid-tapering attempts (P<0.001)
• 11 versus 14 days' hospital stay (P=0.025)

"We performed this study because we were concerned about the lack of safety data on these medications in this cancer patient population," Wang told MedPage Today. "This was a critical question since long-term tumor necrosis factor inhibition for inflammatory bowel disease has been associated with malignancies such as skin cancer and lymphoma."

"While IMDC patients would generally have a shorter exposure than IBD [inflammatory bowel disease] patients, some continue to have IMD for years after cessation of ICI [immune checkpoint inhibitors] and will need longer treatment," she added. "And we don't know for sure if even short-term exposure causes harm."

IMDC is a common immune-related adverse event with ICI therapy. The latter is an effective treatment for some advanced malignancies, but treatment must often be suspended after immune-related gastrointestinal events. Current management of IMDC uses steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) with add-on infliximab or vedolizumab for severe and steroid-refractory cases.

Wang's group performed a retrospective cohort study of cancer patients with IMDC who received selective SIT following steroid therapy from June 2016 to March 2020. A total of 150 patients were enrolled (median age 64; 69% male; 97% Caucasian). The most common cancer types were genitourinary and melanoma (>70%).

Vedolizumab was often administered at three doses or more, while infliximab was mostly limited to one or two doses (P<0.001).

While the efficacy of achieving clinical remission from initial IMDC was equivalent in the two groups at approximately 88%, the lower recurrence rate for vedolizumab was significant (P=0.018). However, vedolizumab was associated with a slight delay in clinical response at 17 versus 10 days (P=0.003).

Factors associated with higher IMDC recurrence included longer duration of ICI (P=0.018), colitis symptoms (P=0.025), and steroid use (P=0.035). In addition, delayed introduction of SIT and infliximab-use alone correlated with more recurrence.

In contrast, multiple doses (three or more of SIT) were significantly correlated with lower IMDC recurrence (P=0.032). Furthermore, vedolizumab alone (P=0.042), higher doses of SIT (P=0.026), and fewer steroid-tapering attempts (P=0.019) were all associated with favorable overall survival (OS).

Whether a patient continues ICI while having SIT depends on a patient's cancer and the comfort level of the oncologist, Wang noted. "If the cancer is more aggressive and starts to progress while the colitis is being treated, some oncologists will say, 'Let's rechallenge -- we don't have a lot of time to waste.' But if the patient is already achieving clinical remission, the oncologist will feel more comfortable suspending ICI."

Overall, vedolizumab also had a better safety profile in terms of less cancer progression and better long-term survival compared with infliximab, Wang said. Although she and her colleagues were unable to quantify the OS difference owing to the diversity of patients, cancers, and treatments in the study cohort, Wang said the ability to continue ICI and also to improve the nutritional status of patients leads to better long-term survival.

"Future treatment for immune-mediated diarrhea and colitis should be judiciously scrutinized by treating physicians to maximize the benefit for patients," she said.

The optimal management strategy for these patients still needs study, but the authors concluded that vedolizumab can significantly improve the disease course of IMDC. A future prospective randomized trial is warranted for further clarification, they said.

Source Reference: Zou F, et al "Comparative study of vedolizumab and infliximab treatment in patients with immune-mediated diarrhea and colitis" ACG 2020; Abstract 2.