Neeraj Narula

McMaster University | McMaster · Division of Gastroenterology

Background The pathogenesis of inflammatory bowel disease (IBD) which includes Crohn’s disease (CD) and ulcerative colitis (UC), is believed to involve activation of the intestinal immune system in response to the gut microbiome among genetically susceptible hosts. IBD has been historically regarded as a disease of developed nations, though in the...

Background To date, no studies have used Artificial Intelligence (AI) to produce standard endoscopic scores for Crohn’s Disease (CD). These scores are essential to clinical practice and have a major cost in clinical trials. Purpose We aimed to re-examine the components of the Simple Endoscopic Score for Crohn’s Disease (SES-CD) and Modified Multip...

Discrepancies in phase two and three studies can result in significant patient and financial burden, as well as the nonapproval of potentially efficacious drugs. We aimed to determine whether this discrepancy exists for clinical trials in inflammatory bowel disease (IBD). Electronic databases (MEDLINE and Embase) and clinical trial repositories wer...

Background and aims: Evaluating histologic outcomes in ulcerative colitis (UC) has become common in recent clinical trials. In this study, we explored the additional value of the combined endpoint of histo-endoscopic mucosal improvement (HEMI) compared to endoscopic improvement (EI) at post-induction (week 14) and post-maintenance (one-year). Met...

Objectives: Perform a systematic review to investigate whether patients with Crohn's disease (CD) and permanent ileostomy (PI) have been included in clinical trials evaluating biologics and small molecules. Results: Of the 81 induction and maintenance trials assessing biologics and oral small molecules in CD, none permitted the enrollment of pat...

Background: Rates of enrolment in clinical trial in inflammatory bowel disease (IBD) have decreased dramatically in recent years. This leads to delays, increased costs, and failures to develop novel treatments. Aims: The aim of this work is to describe the current bottlenecks of IBD clinical trial enrolment and propose solutions. Methods: A ta...

Background Differences in one-year outcomes among early compared to delayed responders to vedolizumab have been demonstrated in ulcerative colitis. However, it is unclear whether differences exist with ustekinumab, and what factors differentiate delayed responders from non-responders. Methods This was a post-hoc analysis of patient-level data from...

Background Several medications have been considered to contribute to the aetiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and risk of developing IBD using the Prospective Urban Rural Epidemiology (PURE) cohort. Methods This was a prospective cohort study of 133,137 individuals between the ag...

Background Scoring indices used in clinical trials for moderate-severe ulcerative colitis (UC) may lack specificity as a prognostic tool. We developed and internally validated a prognostic scoring index for UC patients on therapy that considers baseline patient-reported outcomes, biomarkers, endoscopy, and histology for achieving one-year endoscopi...

Introduction: Several studies have been published on the association between food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC) with some variability in results. We performed a systematic literature review and meta-analysis to study this association. Methods: From Pubmed, Medline and Embase until October 2022, we ident...

Background Indirect treatment comparisons using patient-level data are increasing in popularity within inflammatory bowel disease research. We compared the efficacy of adalimumab and vedolizumab for biologic-naïve moderate–severe ulcerative colitis (UC) using indirect comparisons of phase 3 clinical trials and compared the results to the RCT VARSIT...

Background: We aimed to evaluate the real-world effectiveness and safety of tofacitinib for the treatment of ulcerative colitis (UC). Methods: REMIT-UC is a Canadian multicenter cohort study. Standardized data collection was performed on 334 consecutive adult UC outpatients treated with tofacitinib. The primary outcomes were achievement of clini...

Background: Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and risk of developing IBD using the Prospective Urban Rural Epidemiology (PURE) cohort. Methods: This was a prospective cohort study of 133,137 individuals between the...

Background: In placebo-controlled clinical trials for Crohn's disease (CD), some placebo-treated patients demonstrate improvement. However, it is unclear what factors contribute to placebo response and remission. Methods: This was a post hoc analysis of 3 placebo-controlled clinical trial programs (GEMINI-2, UNITI-1/2, and CLASSIC-1) of moderate...

Background and Aims Perianal fistulizing disease is a common complication of Crohn’s disease (CD), for which new therapies are urgently needed. To assist design of clinical trials for novel therapeutics, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to quantify placebo rates and identify factors influenci...

Background: This analysis evaluates the association between baseline patient-reported symptom (PRS) severity in Crohn's disease (CD), including abdominal pain, stool frequency, general well-being, and achievement of clinical and endoscopic outcomes. We compared baseline PRS to baseline endoscopic scores for the prediction of endoscopic remission (...

Background and Aims Most pharmaceutical clinical trials for inflammatory bowel disease (IBD) are placebo-controlled and require effect size estimation for a drug relative to placebo. We compared expected effect sizes in sample size calculations (SSCs) to actual effect sizes in IBD clinical trials. Methods MEDLINE, EMBASE, CENTRAL, and the Cochrane...

Background We evaluated whether postinduction ulcer size and patient-reported outcome (PRO) severity are associated with the achievement of 1-year endoscopic remission (ER) in patients with Crohn’s disease (CD). Methods This post hoc analysis combined data from several clinical trials including 283 patients with baseline ulcers ≥5 mm with repeat e...

Objective: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). Methods: This study utilized a retrospective, multicenter, multinational, consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant me...

Background: There remains limited data supporting the efficacy of dietary therapy in adults with Crohn's disease (CD). This was a pilot study of the McMaster Elimination diet for CD (MED-CD), which excludes several potentially detrimental ingredients commonly found in the Western diet. Methods: Prospective study in adults with mild-moderately ac...

Although inflammatory bowel disease [IBD] affects an increasingly diverse patient population, most patients in IBD clinical trials are White. Acknowledging current barriers and taking meaningful action is required at multiple levels to improve racial diversity across clinical trials in IBD. Ultimately, improving racial diversity in trials can in tu...

Introduction: It is uncertain whether patients with ulcerative colitis (UC) and delayed symptomatic response to therapy have as robust and durable a response as earlier responders to therapy. We compared clinical outcomes of early and delayed responders to vedolizumab and adalimumab for patients with moderate-severe UC. Methods: This was a post-...

The endoscopic scoring of ulcerative colitis is routinely used for both individual patient management and as an endpoint in clinical trials. The most commonly used scoring system is the Mayo endoscopic sub-score which scores endoscopic disease activity on a scale between 0 and 3. With only four possible scores and consideration of only the most inv...

Background and Aims Treatment options for proctitis are limited. To assist trial design for novel therapeutics, we conducted a systematic review and meta-analysis of proctitis randomized controlled trials (RCTs) to quantify placebo rates and identify factors influencing them. Methods We searched MEDLINE, EMBASE and CENTRAL from inception to June 2...

Background There is a need to better understand the positioning of biologic therapies for long-term outcomes in biologic-naïve Crohn’s disease (CD). We assessed the comparative effectiveness of infliximab and ustekinumab among induction responders for 1-year outcomes. Methods This post hoc analysis included data from 220 biologic-naïve CD particip...

Background High placebo response rates in clinical trials of ulcerative colitis (UC) have been previously reported. However, patient-level analyses have not been performed. We assessed factors associated with clinical and endoscopic placebo response among placebo-treated patients in clinical trials of UC. Methods Post-hoc analysis of pooled clinic...

Background: Patient-reported outcomes (PROs) are increasingly emphasized as endpoints in clinical trials of ulcerative colitis (UC). However, the prognostic value of early improvement in PROs for long-term outcomes remains unclear. Methods: This was a post-hoc analysis of 611 vedolizumab-treated or adalimumab-treated patients in the VARSITY tria...

Background The terminal ileum poses a predilection for Crohn’s disease (CD) but is less susceptible to undergo healing to treatment with biologics and small molecules. This study aimed to evaluate histologic features associated with endoscopic remission (ER). Methods This is a post hoc analysis of patients with moderately to severely active CD, de...

Background: We compared the Simple Endoscopic Score for Crohn's Disease (SES-CD) and Modified Multiplied SES-CD (MM-SES-CD) scores with the Rutgeerts score for predicting clinical recurrence (CR) of postoperative Crohn's disease (CD). Methods: This post hoc analysis of the prospective, multicenter, randomized, double-blind, placebo-controlled tr...

Background and Study AimsThis study aimed to identify whether ulcerative colitis (UC) patients who develop colorectal cancer (CRC) present at earlier stages of CRC and have improved survival if prior to their CRC diagnosis, they underwent intermittent follow-up colonoscopies compared to those who have no follow-up colonoscopies.Methods Patients wit...

Background It is unclear whether improvement in patient‐reported outcomes (PROs) relative to baseline symptom burden in Crohn’s disease (CD) is associated with subsequent endoscopic remission. Aim To evaluate the relationship between dominant PRO resolution post‐induction and achievement of clinical and endoscopic remission. Methods This post‐hoc...

Background and aims: We compared the efficacy of adalimumab, infliximab, ustekinumab, and vedolizumab on the ability to achieve endoscopic healing (EH) after one-year of therapy in moderate-severe Crohn's disease (CD). Methods: Pooled analysis of patient-level data from 299 patients with CD from four clinical trials. Proportions of patients trea...

LINKED CONTENT This article is linked to Wong et al papers. To view these articles, visit https://doi.org/10.1111/apt.16805 and https://doi.org/10.1111/apt.16843

Background Transitioning from pediatric to adult health care is associated with significant psychosocial and clinical morbidity. Adolescents not only transition their medical care, but also experience vast changes in the physical, social, and psychological spheres of their lives. The medical team must help navigate these changes to provide optimal...

Background The modified multiplier of the Simple Endoscopic Score for Crohn’s Disease (MM-SES-CD) is a novel internally validated endoscopic scoring tool that quantifies the endoscopic burden of Crohn’s Disease (CD). The MM-SES-CD considers the same endoscopic parameters and anatomical locations of the commonly used SES-CD, but acknowledges the dif...

Background and aims Current endoscopic scoring indices such as the Simple Endoscopic Score for Crohn’s Disease (SES-CD) quantify the degree of mucosal inflammation in Crohn’s disease (CD) but lack prognostic potential. The Modified Multiplier of the SES-CD (MM-SES-CD) quantifies the endoscopic burden of CD and can be accessed online (https://www.mc...

Objectives 5-aminosalicylate (mesalazine; 5-ASA) is an established first-line treatment for mild-to-moderate ulcerative colitis (UC). This study aimed to model the benefits of optimising 5-ASA therapy. Methods A decision tree model followed 10 000 newly diagnosed patients with mild-to-moderately active UC through induction and 1 year of maintenanc...

Background We compared the efficacy of adalimumab, infliximab, ustekinumab, and vedolizumab for achieving endoscopic healing (EH) in the ileum and colon after one-year of therapy in Crohn’s disease (CD). Methods A pooled analysis of patient-level data from 344 patients with CD from four clinical trial programs was performed. Patients who received...

Background Prevention of post-operative recurrence in Crohn’s disease (CD) is important to avoid further complications requiring additional surgeries. The Rutgeerts’s score is currently the gold standard assessment in clinical trials of post-operative CD. However, the Simplified Endoscopic Score for CD (SES-CD) has not been validated or used clinic...

Background Clinical remission, defined by the Mayo Clinic Score (MCS) or modified MCS, is the accepted regulatory endpoint in drug development for ulcerative colitis (UC). Whilst histologic remission is a more stringent outcome, recent trials have reported numerically higher rates compared to endoscopic or clinical remission rates at the same timep...

Background Current endoscopic scoring indices such as the Simple Endoscopic Score for Crohn’s Disease (SES-CD) quantify the degree of mucosal inflammation in Crohn’s disease (CD) but lack prognostic potential. The Modified Multiplier of the Simple Endoscopic Score for Crohn’s Disease (MM-SES-CD) is an internally validated endoscopic scoring tool th...

Background Biosimilar infliximab (INF-B) has been approved in Canada for Inflammatory Bowel Disease (IBD) for over five years, but real-world descriptions of therapy persistence (discontinuation/switching) comparing INF-B to bio-originator (INF-O) are still scarce. Our objectives are to describe and compare therapy discontinuation/switching of INF-...

Background & Aims We have previously validated a clinical decision support tool (CDST) (vedolizumab CDST [VDZ-CDST]) for clinical and endoscopic remission with VDZ in ulcerative colitis (UC). We aim to expand the validation for predicting histoendoscopic mucosal improvement (HEMI) with VDZ vs adalimumab (ADA). Methods In a post hoc analysis of a c...

Objectives To understand current thinking and clinical decision-making in the treatment and management of patients with mild-to-moderate ulcerative colitis (UC). Methods This multinational, survey-based study was conducted in 2021. Two meetings were held, involving 11 IBD specialists, that used a series of questions and discussion to identify all...

Background and goals: The role of early proactive therapeutic drug level monitoring for anti-tumor necrosis factor therapies is unclear. We aimed to determine whether a week 2 serum trough level in patients with inflammatory bowel disease (IBD) using adalimumab may predict clinical outcomes. Materials and methods: This was a retrospective study...

Background and Aims This study evaluated the minimal clinically important short-term improvement in the Modified Multiplier Simple Endoscopic Score for crohn’s Disease [MM-SES-CD], a novel modified scoring system of the SES-CD, which reliably predicted 1-year endoscopic remission [ER]. Methods This post-hoc analysis of two CD clinical trial progra...

Background Corticosteroids (CS) have been used extensively to induce remission in Crohn’s disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We propose...

Background: Many Crohn's disease patients treated with anti-tumor necrosis factor (TNF) therapies suffer from loss of response over time and require dose escalation. The aim of this study was to evaluate the efficacy and safety of treating anti-TNF experienced Crohn's disease patients with higher maintenance regimens of adalimumab. Methods: In a...

The association between artificial sweetener (AS) consumption and the risk of organ-specific cancers has been debated for decades. We hypothesized that AS consumption is associated with reduced risk of gastrointestinal (GI) cancers. We aimed to test this hypothesis by conducting a systematic review with meta-analysis of the association between AS a...

Background/Aim Helicobacter pylori infects approximately 50% of individuals worldwide. Successful H. pylori eradication is associated with reduced risk of gastric cancer and peptic ulcer disease, among other conditions. We hypothesized that host genetic determinants, especially those affecting gastric pH, might contribute to eradication therapy fai...

Objective To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD). Design Prospective cohort study. Setting 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). Partic...

Background & aims: The prognostic value of histologic scores, grades, and individual histologic sub-components, alone or in combination with endoscopy, for predicting endoscopic improvement (EI) and histo-endoscopic mucosal improvement (HEMI) during maintenance therapy in ulcerative colitis (UC) remains uncertain. Methods: Post-hoc analysis of p...

Introduction Comparative effectiveness studies are needed to help position therapies for ulcerative colitis (UC). We compared the efficacy of infliximab vs. vedolizumab for moderate to severe biologic-naïve UC using patient-level data from clinical trial program datasets. Methods This was a post-hoc analysis of three UC clinical trial programs whi...

This post hoc analysis of the UNITI studies found ustekinumab (UST) did not significantly improve overall extraintestinal manifestations (EIMs) of Crohn's disease compared to placebo-treated patients at weeks 6 and 52. Background and Aims The UNITI trials demonstrated that UST was effective in inducing and maintaining clinical remission in Crohn's...

Background and Aim Vedolizumab is a novel monoclonal antibody used in patients with inflammatory bowel disease, often affecting women of child-bearing age. We aimed to compare maternal and fetal adverse outcomes in pregnancies of women with inflammatory bowel disease exposed to vedolizumab versus those on other treatment. Methods We performed a sy...

Biologic treatment options for Crohn's disease (CD) are increasing and providers will need enhanced support in integrating these therapies into routine practice. Using phase 3 clinical trial programs in CD, we have previously built and validated clinical decision support tools for achieving clinical remission (CREM) with vedolizumab and ustekinumab...

Background and aims: Crohn's disease (CD) patients who previously failed anti-TNF therapy are at higher risk of treatment failure with subsequent biologics. This study aims to determine the effectiveness and safety of higher maintenance dose regimens of adalimumab compared to standard doses in CD patients who failed anti-TNF. Methods: In this re...

Background Early life exposures impact immune system development and therefore the risk of immune-mediated diseases, including inflammatory bowel disease (IBD). We systematically reviewed the impact of pre-, peri‑, and postnatal exposures up to the age of five years on subsequent IBD diagnosis. Methods We identified case-control and cohort studies...

Introduction: Cost-effectiveness of biomarker- vs endoscopy-based treat-to-target monitoring in Crohn's disease (CD) is unknown. Methods: A microsimulation model for CD was built to simulate biomarker (fecal calprotectin) vs endoscopy-based monitoring in a treat-to-target fashion. Published literature in combination with patient-level data from...

LINKED CONTENT This article is linked to Mesonero et al paper. To view this article, visit https://doi.org/10.1111/apt.16315

Background and Aims Comparative effectiveness have become increasingly important to help position therapies for inflammatory bowel disease. We compared the efficacy and rapidity of onset of action of infliximab vs. ustekinumab induction therapy for moderate to severe biologic-naïve Crohn’s disease (CD) using patient-level data from randomized contr...

Background and aims: The Simple Endoscopic Score for Crohn's disease (SES-CD) is the primary tool for measurement of mucosal inflammation in clinical trials but lacks prognostic potential. We set to develop and validate a modified multiplier of the SES-CD (MM-SES-CD), which takes into consideration each individual parameter's prognostic value for...

Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease (CD) related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programs examining outcomes with inflix...

Background The relationship between older age and extraintestinal manifestations (EIMs) in patients with inflammatory bowel disease (IBD) remains unknown. Aims This study aims to determine whether older age is associated with increased risk of EIMs in IBD patients. Methods This was a retrospective study of IBD patients seen at the McMaster Univer...

Technological advances now permit self-management strategies using mobile applications which could greatly benefit patient care. The purpose of this study was to investigate whether the use of the inflammatory bowel disease (IBD) digital health monitoring platform, HealthPROMISE, leads to better quality of care and improved health outcomes in IBD p...

Background: Histologic remission in ulcerative colitis (UC) patients may be associated with positive outcomes. It is unclear whether UC patients in endoscopic remission obtain additional benefit from achieving histologic remission. Aim: To evaluate the relationship between time to relapse and histological activity among UC patients in endoscopic...

Background and Aims It is unclear however whether early symptom improvement in Crohn’s disease (CD) provides any prognostic information for patients long-term. This paper aims to investigate the relationship between early patient reported outcomes (PROs) after completion of induction of infliximab and their relationship with long-term clinical remi...

Background: Medications used to treat inflammatory bowel disease (IBD) have significantly improved patient outcomes and delayed time to surgery. However, some of these therapies are recognized to increase the general risk of infection and have an unclear impact on postoperative infection risk. Objectives: To assess the impact of perioperative IB...

Objectives: There is need for biomarkers as predictors of outcome to medical treatment in Crohn's disease. The purpose of this study was to evaluate the predictive performance of fecal calprotectin for short- and long-term clinical and endoscopic outcomes. Methods: This post-hoc analysis of the UNITI/IM-UNITI studies (NCT01369329, NCT01369342, a...