Neeraj Narula, MD, on Predicting Response to Biologics in Ulcerative Colitis

In this podcast, Dr Narula discusses his recent research into the potential for early changes in epithelial neurophilic infiltrate to predict the long-term response to biologics among patients with ulcerative colitis.

Neeraj Narula, MD, is director of the Inflammatory Bowel Disease Center at McMaster University in Hamilton, Ontario.

TRANSCRIPT:

GASTROENTEROLOGY LEARNING NETWORK:  Hello, everyone and welcome to another podcast from the Gastroenterology Learning Network. I'm your moderator, Rebecca Mashaw. Today, I'm here with Dr. Neeraj Narula, director of the Inflammatory Bowel Disease Center at McMaster University in Hamilton, Ontario.

He's going to talk about the results of a recent study he and his colleagues conducted into whether early changes in epithelial-neutrophilic infiltrate may help predict the long-term response to biologics among patients with ulcerative colitis. Thank you for joining us today, Dr. Narula.

Dr. Neeraj Narula:  My pleasure, Rebecca.

GLN:  What was the objective of your study?

Dr. Narula:  Histology is becoming a topic of high interest in inflammatory bowel disease, but we're still trying to understand how relevant histologic healing and changes that we observe in ulcerative colitis patients really are.

The purpose of this study was to determine whether there's any individual histologic features of ulcerative colitis at baseline or if changes in these features in response to induction therapy with biologics could predict which patients would go on to achieve endoscopic improvement during maintenance therapy with biologics.

GLN:  Your article mentions that your study is a post-hoc analysis of participants from the VARSITY trial, vedolizumab versus adalimumab. What sort of analyses did you conduct?

Dr. Narula:  Briefly, we ran several receiver operating characteristic curves, which can help us determine which potential predictors have the highest sensitivity and specificity for outcomes of interest. Then we ran multivariable logistic regression models to adjust for other confounding factors.

GLN:  What did you find out about the prognostic value of these assessments?

Dr. Narula:  We found that neutrophils in the epithelial surface, and in particular change in these neutrophils in response to biologic therapy, were the strongest prognostic factor for predicting who would achieve endoscopic improvement and who would not.

GLN:  The VARSITY trial was the head-to-head trial of vedolizumab and adalimumab. Do you believe that other biologics would show similar results?

Dr. Narula:  We observed similar patterns with both patients treated with vedolizumab and with adalimumab, so I do suspect we will see similar results using other biologics as well.

GLN:  What are the implications of your study's results in treatment of patients with ulcerative colitis?

Dr. Narula:  Currently, histopathologic assessment in ulcerative colitis has evolved, and there are numerous histologic scores and indices available, including the Geboes score, the Robarts Histopathology Index, and the Nancy score.

There are some concerns about poor intraobserver reliability and some difficulty in standardizing reporting methods using some of these scores, which have made it challenging for these to be taken up in clinical practice and has raised some uncertainty as a result about whether histologic remission should be a treatment target.

However, as our study demonstrated, improvement or lack of improvement in the epithelial-neutrophilic infiltrate actually was more prognostic than changes in these overall scores, like the Geboes or the RHI. So we could find targeting absence of neutrophils in ulcerative colitis to be more feasible, practical, and likely a relevant target when assessing patients with ulcerative colitis.

GLN:  So this could prove to be a valuable tool.

Dr. Narula:  Yes, definitely, both in clinical trials as well as clinical practice.

GLN:  I suppose that leads naturally into how practicing gastroenterologists might use this information to help optimize care for their patients with ulcerative colitis.

Dr. Narula:  It may be too early to make changes in routine clinical practice just based on these findings alone. I do think we need to see some prospective time-series studies, which help clarify the timeline in which endoscopic and histologic healing actually occur.

Further, we need some assessment to understand if neutrophilic activity is associated with improvement in other longer-term outcomes such as hospitalization, cancer, or colectomy to further validate its importance as a treatment target.

I think once we see further studies which validate this as a treatment target, it's something that could be quite easily be incorporated into routine clinical practice as a potential treatment target.

GLN:  Do you have more research planned on this topic yourself?

Dr. Narula:  We do have another study plan, which is looking at a composite index, including clinical symptoms, endoscopic components, as well as histologic components to see if it can prove to provide further prognostic value.

GLN:  Thanks very much for discussing this with us. It's quite interesting and we look forward to talking with you about the results of your upcoming research.

Dr. Narula:  Thanks for having me, Rebecca.

REFERENCE:

Narula N, Wong ECL, Colombel JF, et al. Early change in epithelial neutrophilic infiltrate predicts long-term response to biologics in ulcerative colitis. Clin Gastroenterol Hepatol. Published online July 02, 2021.DOI: https://doi.org/10.1016/j.cgh.2021.07.005