Acute Gastroenteritis in the Etiology of Inflammatory Bowel Disease: Systematic Review and Meta-Analysis

Introduction Inflammatory bowel disease (IBD) consists of a spectrum of disorders including ulcerative colitis (UC) and Crohn’s disease (CD), with a rising incidence worldwide. However, despite this prevalence the etiology of IBD remains uncertain. It has been suggested that an episode of gastroenteritis may precipitate IBD. Methods Studies were identified using a literature search of Pubmed/Medline and Embase/Ovid. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The primary outcome was incidence of new-onset IBD after gastro-enteritis. Secondary outcomes included incidence of IBD after bacterial, viral, and parasitic gastro-intestinal infections. Results Eleven studies (n=923,608 patients) were included. Four studies assessed patients with gastroenteritis, subsequently developing IBD as the primary outcome. Patients with gastroenteritis had a higher incidence of subsequent IBD but this did not reach statistical significance (OR 3.81, 95%CI 0.52-27.85, p=0.19, see Figure 2). Seven studies examined the incidence of antecedent gastroenteritis (primary outcome) in patients with a confirmed diagnosis of IBD, compared to the controlled population. There was no difference between incidence of antecedent gastroenteritis across the two population groups (OR 1.07, 95%CI 0.55-2.08, p=0.85). There was no association between IBD and bacterial, viral or parasitic infections. Conclusion In summary, our meta-analysis has shown that there is considerable heterogeneity in the literature regarding the role of gastroenteritis in the development of IBD. Further higher quality studies need to be performed to ascertain the true nature of this.

A Patient-Prioritized Agenda for Information Needs During the COVID-19 Pandemic: A Qualitative Study of Patients With Inflammatory Bowel Disease

Background Patients with inflammatory bowel disease (IBD) may be at risk for complications due to the COVID-19 pandemic. We performed a qualitative study to better understand IBD patient experiences and concerns when navigating the COVID-19 pandemic, with the goal of prioritizing patients’ information needs. Methods We conducted a series of semistructured virtual focus groups at 6 months, then member checking focus groups 1 year into the COVID-19 pandemic. We included questions on patients’ experiences navigating the pandemic with IBD, differences in their experience as compared to peers, their concerns and fears, as well as preferred information sources. Transcribed focus groups were coded and content analyzed to summarize key areas of interest and identify themes. We focused on 4 areas in our content analysis process: fears, challenges, information preferences, and research questions. Results A total of 26 IBD patient participants were included in the initial focus groups. Findings highlighted the many challenges faced by patients during the COVID-19 pandemic, ranging from access (bathrooms, medications, healthcare) to significant fears and concerns surrounding medications used for IBD worsening risks of COVID-19. Research questions of importance to patients centered on understanding risks for COVID-19 complications, particularly pertaining to medication utilization, with a shift over time toward understanding COVID-19 vaccination. In our member checking focus groups (n = 8 participants), themes were reiterated, with a central focus of research questions pertaining to COVID-19 vaccination. Conclusions Information needs for patients during the COVID-19 pandemic centered upon understanding disease-specific risks. Identified challenges and fears will inform future research agendas and communication with patients.

The effect of early versus delayed initiation of adalimumab on remission rates in patients with Crohn’s disease with poor prognostic factors: The MODIFY study

Background Data on the effectiveness of anti–tumour necrosis factor medications in patients with Crohn’s disease with poor prognostic factors are scarce. This study aimed to generate real-world evidence on the effect of early (≤24 months after diagnosis) versus delayed (>24 months) initiation of adalimumab on the 26-week remission rate (Harvey-Bradshaw Index ≤4) in these patients. Methods This multicentre, retrospective, chart-review study performed in 10 Greek hospitals enrolled adult patients with moderate to severe Crohn’s disease (Harvey-Bradshaw Index ≥8) with ≥3 poor prognosis factors who were initiated on adalimumab ≥12 months before enrolment. A sample size of 164 patients (early:delayed cohort allocation ratio, 30:70) was required to address the primary endpoint. Results Eligible patients (n=171) were consecutively enrolled. In the early versus delayed cohorts, the 26-week remission rates (off steroids) using the last-observation-carried-forward imputation method were 60.7% (37/61) versus 47.2% (50/106), respectively (Δ=13.5%, p=0.044). The respective remission rates were 61.2% versus 42.4% among anti–tumour necrosis factor–naive patients (p=0.023) and 58.3% versus 53.2% among anti–tumour necrosis factor–experienced patients (p=0.374). The 52-week remission rates using as-observed data were 78.8% and 60.3%, and the intestinal resection rates were 6.5% and 11.9% in the early versus delayed ADL cohorts, respectively. Conclusions Patients with Crohn’s disease with poor prognostic factors who received early versus delayed treatment with adalimumab achieved higher clinical response and remission rates. This effect was more pronounced in those patients who were bio-naive and steroid-dependent/refractory with concurrent extraintestinal manifestations than those who were not.

Home Infusions for Inflammatory Bowel Disease are Safe: United States Experience and Patient Perspectives

Background Home-infusions (HI) for biologic medications are an option for inflammatory bowel disease (IBD) patients in the United States (US). We aimed to describe the population receiving HI and report patient experience with HI. Methods We conducted a retrospective cohort study in the Quintiles-IMSLegacy PharMetrics Adjudicated Claims Database from 2010-2016 to describe the population receiving infliximab and vedolizumab HI and determine predictors for an urgent/emergent visit post-HI. We then administered a cross-sectional survey to IBD-Partners Internet-based cohort participants to assess knowledge and experience with infusions. Results We identified claims for 11,892 conventional infliximab patients, 1,573 home infliximab patients, 438 conventional vedolizumab patients and 138 home vedolizumab patients. There were no differences in demographics or median charges with infliximab home and conventional infusions. Home vedolizumab infusions had a greater median charge than conventional vedolizumab infusion. Less than 4% of patients had an urgent/emergent visit post-HI. Charlson comorbidity index >0 (OR:1.95, 95% CI:1.01-3.77) and Medicaid (OR:3.01, 95%CI:1.53-5.94) conferred significantly higher odds of urgent/emergent visit post-HI. In IBD-Partners, 644 IBD patients responded; 56 received HI. The majority chose HI to save time and preferred HI to conventional infusions. Only 2 patients reported an urgent/emergent visit for HI-related problems. Conclusions HI appears to be safe in IBD patients receiving infliximab and vedolizumab. However, patients with fewer resources and more co-morbidities are at increased risk for an urgent/emergent visit post-HI. The overall patient experience with HI is positive. Expansion of HI may result in decreased therapy-related logistic burden for carefully selected patients.

Palliative Care in Inflammatory Bowel Disease: A New Partnership

Background Palliative care is being increasingly recognized for benefitting patients with a wide spectrum of chronic serious medical conditions. Methods Care models and principles of palliative care for patient with inflammatory bowel disease were explored. Results The use of a structured and systematic approach for emotionally laden conversations and the “Total Pain” paradigm are examples of palliative care expertise that can be applied through either primary or consultative palliative care models. Conclusions Palliative care should be considered in clinical practice and as a topic for further scholarly investigation to further define its role and benefits.

Retrospective Cohort Study Comparing Infliximab-dyyb and Infliximab in Biologic Naïve Patients with Inflammatory Bowel Disease in the United States

Background Real-world assessments of biosimilars are needed to understand their effectiveness and safety in practice settings that may differ from those seen in clinical trials or healthcare systems in different countries. Objective To assess the effectiveness and safety of a biosimilar (infliximab-dyyb) and its reference product (infliximab) in patients with inflammatory bowel disease (IBD) in the United States (US). Methods We conducted a retrospective cohort study of biologic-naïve patients with IBD who started treatment with infliximab-dyyb or infliximab. The study included 3,206 patients identified through electronic health records in a US integrated healthcare delivery system. The effectiveness outcome was a composite of IBD-related surgery, IBD-related emergency room visit, and IBD-related hospitalization within 12 months of initiation. Safety outcomes included incidence of any or serious infection, cancer, acute liver dysfunction, and tuberculosis. We used a non-inferiority test with an upper-limit margin of 10% to analyze effectiveness. Doubly robust methods incorporating Cox proportional hazard regression with standardized inverse probability of treatment weighting were used to analyze both effectiveness and safety outcomes. Results The composite effectiveness outcome occurred in 107 of 870 patients (12.3%) in the infliximab-dyyb and 379 of 2,336 patients (16.2%) in the infliximab groups. Infliximab-dyyb was non-inferior (P < .01) and was not different (HR 0.81;CI 0.65-1.01;P = .06) to infliximab. Safety outcomes were not different between infliximab-dyyb and infliximab for any infections (HR 1.01;CI 0.86-1.17;P = .95), serious infections (HR 0.83;CI 0.54-1.26;P = .38), cancers (HR 0.83;CI 0.44-1.54;P = .55), and tuberculosis (HR 0.59;CI 0.10-3.55;P = .57). Conclusion Initiation of infliximab-dyyb was non-inferior to infliximab among biologic-naïve patients with IBD in an US integrated healthcare delivery system. Lay summary In this US-based, retrospective, multi-center, cohort study of 3,206 biologic-na�ve patients with IBD, treatment with the biosimilar infliximab-dyyb was non-inferior to reference product infliximab for the effectiveness composite of IBD-related surgery, IBD-related emergency room visit, and IBD-related hospitalization.

Development of a novel drug delivery system to deliver drugs directly to the colonic mucosa, resulting in improved efficacy and reduced systemic exposure for the treatment of ulcerative colitis

Despite recent drug approvals for the treatment of inflammatory bowel diseases (IBD), there remains a high unmet need for new technologies that can increase drug efficacy by improving site-specific drug delivery while reducing systemic exposure. These technologies must address challenges with formulation; in particular, drugs that are liquid, peptides or proteins are difficult to formulate using existing delayed and extended oral release technologies. They also have the potential to improve efficacy and reduce systemic exposure for certain drugs by delivering higher doses directly to the site of inflammation. A novel drug delivery system (DDS2) is being developed for delivery at a pre-specified part of the gastrointestinal tract. This autonomous mechanical capsule uses an algorithm based on reflected light to deliver soluble formulations of drugs to the predefined location. This system has significant advantages over other traditional delayed release oral formulations because it functions independently of human physiological variables such as pH and transit time and can deliver liquid formulations, peptides, and proteins. Such a system can ensure a predictable high luminal drug exposure and limited degradation or systemic absorption in the upper gastrointestinal tract and would therefore be ideal for treatment of disorders such as IBD and colon cancer.