Functional gastrointestinal symptoms in patients with inflammatory bowel disease: A clinical challenge

Description The purpose of this clinical practice update review is to describe key principles in the diagnosis and management of functional gastrointestinal (GI) symptoms in patients with inflammatory bowel disease (IBD). Methods The evidence and best practices summarized in this manuscript are based on relevant scientific publications, systematic reviews, and expert opinion where applicable. Best practice advice 1 A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging). Best practice advice 2 In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management. Best practice advice 3 Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation. Best practice advice 4 Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns. Best practice advice 5 A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy. Best practice advice 6 Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms. Best practice advice 7 Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation. Best practice advice 8 Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD. Best practice advice 9 Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided. Best practice advice 10 Probiotics may be considered for treatment of functional symptoms in IBD. Best practice advice 11 Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder. Best practice advice 12 Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD. Best practice advice 13 Physical exercise should be encourage in IBD patients with functional GI symptoms. Best practice advice 14 Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD

Protein glycosylation as a diagnostic and prognostic marker of chronic inflammatory gastrointestinal and liver diseases

Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of immune cells, and alterations have been associated with inflammatory conditions. For example, specific glycans regulate T-cell activation, structures, and functions of immunoglobulins; interactions between microbes and immune and epithelial cells; and malignant transformation in the intestine and liver. We review the effects of protein glycosylation in regulation of gastrointestinal and liver functions, and how alterations in glycosylation serve as diagnostic or prognostic factors, or as targets for therapy

COVID-19 and Inflammatory Bowel Disease: Lessons Learned, Practical Recommendations, and Unanswered Questions

On March 11, 2020 the World Health Organization declared the 2019 novel coronavirus (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) epidemic a global pandemic. Physicians, scientists, and patients scrambled to gain an understanding of the implications of this dire situation, and societies and organizations tried to provide guidance of best practices and precautions. In the inflammatory bowel disease community (IBD), the International Organization for the study of IBD (IOIBD) convened their expert members and performed a RAND panel assessment to develop recommendations for patients and providers. Others developed an international open registry to collect data about patients with IBD who developed Coronavirus Disease (COVID-19), the Surveillance Epidemiology of COVID-19 Under Research Exclusion (SECURE-IBD), in order to collect evidence on how COVID-19 impacted IBD patients. To date, SECURE-IBD has amassed 3,493 cases with outcomes3 and published initial analyses. In addition, there were multiple articles published with individual or multi-center experiences, city or regional experiences, and many case reports about IBD or immunemediated disease outcomes. Separately, there was significant activity by translational and basic scientists working to define and describe the pathophysiology of SARS-CoV-2 infections

De-escalation of immunomodulator and biological therapy in inflammatory bowel disease.

Treatment strategies for inflammatory bowel disease (IBD) focus on the induction and long-term maintenance of deep remission to avoid complications of active disease and improve long-term outcomes. Medical therapies for IBD, notably the increasingly widespread use of biological therapy, are often effective at controlling disease, but these drugs are associated with substantial adverse events, which together with other factors-including increasing treatment costs and patient preferences-leads to concerns regarding indefinite use of medical therapy. Consequently, the need to consider the safety and feasibility of drug de-escalation once IBD remission has been achieved is clear. Here, we review the current evidence surrounding de-escalation of immunomodulator and biological therapy in Crohn's disease and ulcerative colitis. We discuss strategies for de-escalation, including the selection of patients who are appropriate for treatment de-escalation and the use of proactive drug monitoring, and review the evidence on subsequent optimal follow-up. We conclude by proposing an algorithm to guide de-escalation decisions, and highlight future perspectives, including the potential effect of emerging medication and personalised medicine for these diseases

Treat to Target: A Proposed New Paradigm for the Management of Crohn's Disease.

International audience: The traditional management of CD, based on progressive, step-wise treatment intensification with re-evaluation of response according to symptoms, does not improve long-term outcomes of CD and places patients at risk for bowel damage. The introduction of novel therapies and the development of new approaches to treatment in rheumatoid arthritis led to better outcomes for patients. Prominent among these is a "treat to target" strategy that is based on regular assessment of disease activity using objective clinical and biological outcome measures and the subsequent adjustment of treatments. This approach is complementary to the concept of early intervention in high risk patients. This review evaluates current literature on this topic and proposes a definition for the concept treating to targets for Crohn's disease

Agreement of site and central readings of ileocolonoscopic scores in Crohn's disease: comparison using data from the EXTEND trial

Background and AimsCentralized endoscopic scoring may reduce variability, but evidence is lacking in patients with Crohn’s disease. We assessed the agreement of endoscopic scorings between site endoscopists and one central reader by using data from the adalimumab Crohn’s disease clinical trial EXTEND.MethodsAgreement between readers for Crohn’s Disease Endoscopic Index of Severity (CDEIS)–scored endoscopies from 6 sites and Simple Endoscopic Score for Crohn’s Disease (SES-CD)–scored endoscopies from 19 sites in EXTEND was evaluated at baseline and weeks 12 and 52. Agreement on total scores was calculated by using intraclass correlation coefficient (ICC). Kappa statistic or Spearman correlation coefficient measured the agreement between readers for each ileocolonic segment on CDEIS variables including deep ulceration, surface involved, and ulcerated surface and SES-CD variables including ulcerated surface, size of ulcers, and affected surface.ResultsICCs on mean scores at baseline and weeks 12 and 52 were 0.78, 0.92, and 0.86 (CDEIS), and 0.77, 0.86, and 0.82 (SES-CD), respectively. Site endoscopists consistently reported higher scores. High agreement was observed for most segments and all time points for CDEIS variables and SES-CD large ulcers. Weak agreement occurred for the right side of the colon at all time points for CDEIS deep ulceration and SES-CD large ulcers and at baseline and week 12 for CDEIS ulcerated surface. Fair/moderate agreement occurred for SES-CD ulcerated surface and moderate/high agreement for affected surface for all segments and time points.ConclusionsSite and central readers showed high agreement on total CDEIS and SES-CD scores overall, whereas variability for individual segments was observed. Weakest agreement occurred at baseline, with a greater difference for SES-CD than for CDEIS score. (Clinical trial registration number: NCT00348283.

The impact of vedolizumab on COVID-19 outcomes among adult IBD patients in the SECURE-IBD registry

Introduction The impact of immune-modifying therapies on outcomes of Coronavirus disease of 2019 (COVID-19) is variable. The purpose of this study was to determine the impact of vedolizumab (VDZ), a gut-selective anti-integrin, on COVID-19 outcomes in inflammatory bowel disease (IBD) patients. Methods Using data from the Surveillance of Coronavirus Under Research Exclusion for IBD (SECURE-IBD), an international registry of IBD patients with confirmed COVID-19, we studied the impact of VDZ on COVID-19 hospitalization and severe COVID-19 (intensive care unit stay, mechanical ventilation and/or death). Results Of 3,647 adult patients on any IBD medication in the registry, 457 (12.5%) patients were on VDZ. On multivariable analyses using backward selection of covariates, VDZ use was not associated with hospitalization or severe COVID-19 when comparing to patients on all other medications [adjusted odds ratio (aOR) 0.87; 95% confidence interval (CI) 0.71, 1.1 and aOR 0.95; 95% CI 0.53; 1.73, respectively]. On comparing VDZ monotherapy to anti-TNF monotherapy, the odds for hospitalization, but not severe COVID-19, were higher (aOR CI 1.39; 95% CI 1.001, 1.90 and aOR 2.92; 95% CI 0.98, 8.71, respectively). In an exploratory analysis, VDZ monotherapy, compared to anti-TNF monotherapy, was associated with new-onset GI symptoms at the time of COVID-19, especially among patients whose IBD was in remission. Conclusions COVID-19 outcomes among IBD patients on VDZ are comparable to those on all other therapies. Hospitalization, but not severe COVID-19, is more likely with VDZ monotherapy than with anti-TNF monotherapy. Overall, VDZ appears to be safe in IBD patients with COVID-19

Factors Associated With Short- and Long-Term Outcomes of Therapy for Crohn’s Disease

Background & AimsOur post hoc analysis assessed the association of early (at weeks 26–30) clinical, endoscopic, biologic, and pharmacokinetic outcomes with corticosteroid-free remission at week 50 (CSFR50); CSFR50 was observed in 55.2% and 65.4% of patients treated with infliximab, alone or in combination with azathioprine, respectively.MethodsWe analyzed data from 203 patients: 96 received infliximab monotherapy and 107 received combination therapy. Receiver operating characteristic analysis was used to set cut-off points for the week 30 trough serum infliximab concentration (SIC30) and percentage change, from baseline, in the C-reactive protein (CRP) level at week 26, to predict CSFR50. Univariate and multivariate procedures analyzed predictive parameters of CSFR50 (odds ratio [OR] and 95% confidence interval [CI]). Mucosal healing (MH, zero ulcers) and CRP normalization (<8.0 mg/L) also were assessed.ResultsTrough SIC30 was higher in patients with than without CSFR50. Patients given combination therapy had higher trough SIC30s than those given monotherapy. Median trough SIC30 was significantly higher in patients with than without CSFR50 among those on infliximab monotherapy (2.14 vs 0.80 μg/mL; P = .006), but not for those on combination therapy (3.56 vs 3.54 μg/mL; P=.31). In patients with increased baseline levels of CRP (n = 120), corticosteroid-free remission at week 26 (CSFR26) (OR, 4.09; 95% CI, 1.65–10.11), and trough SIC30s of 3.0 μg/mL or greater (OR, 3.20; 95% CI, 1.38–7.42) were associated significantly with CSFR50. In patients evaluable for MH (n = 123), trough SIC30s of 3.0 μg/mL or greater (OR, 3.34; 95% CI, 1.53–7.28) and CRP normalization (OR, 2.69; 95% CI, 1.10–6.54) were associated significantly with MH at week 26 (MH26). Furthermore, CSFR26 (OR, 4.43; 95% CI, 1.81–10.82) and MH26 (OR, 3.01; 95% CI, 1.33–6.81) were associated significantly with CSFR50.ConclusionsTrough SIC30 is associated positively with MH26; CSFR26 and MH26 are independent predictors of CSFR50. Trough SIC30 of 3.0 μg/mL or greater early during maintenance treatment is an important determinant of clinical and endoscopic Crohn’s disease outcomes. ClinicalTrials.gov number, NCT00094458

Presence of Comorbidities Associated with Severe Coronavirus Infection in Patients with Inflammatory Bowel Disease

Background Comorbidities increase the risk of coronavirus disease 2019 (COVID-19) hospitalization and mortality. As many comorbidities are common in patients with inflammatory bowel diseases (IBD), we sought to investigate the effects of comorbidities in these patients on infection severity. Aim To evaluate association between individual comorbidities and COVID-19 infection severity among patients with IBD. Methods Data were obtained from SECURE-IBD, an international registry created to evaluate COVID-19 outcomes in patients with IBD. We used multivariable regression to analyze associations between eleven non-IBD comorbidities and a composite primary outcome of COVID-19-related hospitalization or death. Comorbidities were first modeled individually, adjusting for potential confounders. Next, to determine the independent effect of comorbidities, we fit a model including all comorbidities as covariates. Results We analyzed 2,035 patients from 58 countries (mean age 42.7 years, 50.6% male). A total of 538 patients (26.4%) experienced severe COVID-19. All comorbidities but a history of stroke and obesity were associated with severe infection in our initial analysis, with adjusted odds ratios ranging from 1.9 to 3.7. In a model including all comorbidities significantly associated with the composite outcome in the initial analysis, as well as other confounders, most comorbidities remained significant, with the highest risk in chronic kidney disease and chronic obstructive pulmonary disease. Conclusion Many non-IBD comorbidities are associated with a two to threefold increased risk of COVID-19 hospitalization or death among patients with IBD. These data can be used to risk-stratify and guide treatment and lifestyle decisions during the ongoing pandemic