Background and aims Patients infected with the SARS-CoV-2 usually report fever and respiratory symptoms. However, multiple gastrointestinal (GI) manifestations such as diarrhoea and abdominal pain have been described. The aim of this study was to evaluate the prevalence of GI symptoms, elevated liver enzymes and mortality of patients with COVID-19. Methods A systematic review and meta-analysis of published studies that included a cohort of patients infected with SARS-CoV-2 were performed from 1 December 2019 to 15 December 2020. Data were collected by conducting a literature search using PubMed, Embase, Scopus, and Cochrane according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We analysed pooled data on the prevalence of individual GI symptoms and elevated liver enzymes and performed subanalyses to investigate the relationship between GI symptoms/elevated liver enzymes, geographical location, mortality, and intensive care unit (ICU) admission. Results The available data of 78 798 patients positive for SARS-CoV-2 from 158 studies were included in our analysis. The most frequent manifestations were diarrhoea (16.5%, 95% CI 14.2% to 18.4%), nausea (9.7%, 95% CI 9.0% to 13.2%) and elevated liver enzymes (5.6%, 95% CI 4.2% to 9.1%). The overall mortality and GI mortality were 23.5% (95% CI 21.2% to 26.1%) and 3.5% (95% CI 3.1% to 6.2%), respectively. Subgroup analysis showed non-statistically significant associations between GI symptoms/elevated liver enzymes and ICU admissions (OR=1.01, 95% CI 0.55 to 1.83). The GI mortality was 0.9% (95% CI 0.5% to 2.2%) in China and 10.8% (95% CI 7.8% to 11.3%) in the USA. Conclusion GI symptoms/elevated liver enzymes are common in patients with COVID-19. Our subanalyses showed that the presence of GI symptoms/elevated liver enzymes does not appear to affect mortality or ICU admission rate. Furthermore, the proportion of GI mortality among patients infected with SARS-CoV-2 varied based on geographical location.

Crohn’s disease (CD) and ulcerative colitis (UC), known as inflammatory bowel diseases (IBD), are characterized by chronic inflammation of the gastrointestinal tract. Over the last two decades, numerous medications have been developed and repurposed to induce and maintain remission in IBD patients. Despite the approval of multiple drugs, the major recurring issues continue to be primary non-response and secondary loss of response, as well as short- and long-term adverse events. Most clinical trials show percentages of response under 60%, possibly as a consequence of strict inclusion criteria and definitions of response. That is why these percentages appear to be more optimistic in real-life studies. A therapeutic ceiling has been used as a term to define this invisible bar that has not been crossed by any drug yet. This review highlights novel therapeutic target agents in phases II and III of development, such as sphingosine-1-phosphate receptor modulators, selective Janus kinase inhibitors, anti-interleukins, and other small molecules that are currently under research until 1 January 2023. Emerging treatments for CD and UC that have just received approval or are undergoing phase III clinical trials are also discussed in this review.

Background: The medical treatment of fistulizing Crohn’s disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical treatment of fistulizing CD. The purpose of this study is to compare the efficacy of biologic therapies in inducing response and remission in fistulizing CD. Methods: We performed a systematic review of the EMBASE, MEDLINE, and Cochrane Central databases from inception to December 2021. Inclusion criteria were any randomized controlled trials (RCTs) that evaluated the efficacy of biologic therapies against an active comparator or placebo for induction of response or remission in adults with fistulizing CD. The proportion of patients with fistula response or remission, as defined by each clinical trial, was our primary study outcome. A Bayesian random-effects network meta-analysis was used to measure treatment effects and results were reported as odds ratio (OR) and 95% confidence interval (CI). Results: In our analysis, 10 studies were included, and all were RCTs. Infliximab was superior to adalimumab in inducing response (OR, 0.24; 95% CI, 0.06-0.99) but not in inducing remission (OR, 0.31; 95% CI, 0.04-2.27). Tumor necrosis factor antagonists were superior to placebo in the induction of response (OR, 0.51; 95% CI, 0.35-0.750) and remission (OR, 0.36; 95% CI, 0.22-0.58). Infliximab was superior to placebo in inducing response (OR, 0.36; 95% CI, 0.17-0.75) and remission (OR, 0.17; 95% CI, 0.03-0.87). Ustekinumab was superior to placebo in inducing response (OR, 0.48; 95% CI, 0.26-0.860) but not in inducing remission (OR, 0.50; 95% CI, 0.13-1.93). When comparing biologic therapies against each other, there was no statistical difference in inducing remission. Vedolizumab was not superior to placebo in inducing remission (OR, 0.32; 95% CI, 0.04-2.29). Certolizumab was not superior to placebo in inducing response (OR, 0.78; 95% CI, 0.40-1.55) or remission (OR, 0.78; 95% CI, 0.40-1.55). Conclusions: Tumor necrosis factor antagonists are effective in inducing response and remission in fistulizing CD. Infliximab was superior to adalimumab for inducing response but not for inducing remission. Ustekinumab is effective in the induction of response but not in the induction of remission. When compared against each other, biologic therapies showed no significant difference in the induction of remission. Based on the available data, infliximab is the preferred first-line treatment. As for other biologics, the limited published data do not allow us to make firm recommendations. This study supports current practice and emphasizes the need for dedicated RCTs to evaluate the efficacy of biologic therapies in fistulizing CD.

The clinical impact of histological remission on short- and long-term clinical outcomes in patients with inflammatory bowel disease (IBD) is not well established. We assessed risk of clinical relapse, hospitalization, and need for surgery in patients achieving histological remission in comparison with active histological disease. A systematic review was conducted using MEDLINE, Scopus, Cochrane CENTRAL, EMBASE, and conference abstracts from inception to November 2022. Our main outcome was the rate of clinical relapse in patients with IBD who reached histological remission vs patients with active histological disease. Secondary outcomes were clinical complications of IBD such as hospitalization and need for surgery. The endpoints were investigated at 2 time points, 6 to 12 months (short term) and >12 months (long term). Short-term outcome analysis showed that the risk of clinical relapse was significantly higher in ulcerative colitis patients with active histological disease in comparison with patients at histological remission (risk ratio [RR], 2.41; 95% confidence interval [CI], 1.69-3.44; P < .01). The risk of hospitalization in ulcerative colitis patients was not significant among the 2 groups (RR, 4.22; 95% CI, 0.91-19.62; P = .07). Long-term outcome analysis demonstrated that the risk of clinical relapse (RR, 2.07; 95% CI, 1.55-2.76; P < .01), need for surgery (RR, 3.14; 95% CI, 1.53-6.45; P < .01), and hospitalization (RR, 2.52; 95% CI, 1.59-4.00; P < .01) was significantly higher in patients with active histological disease. Histological remission in IBD represents an important therapeutic goal that is not yet routinely pursued in clinical practice. In our study, patients who achieved histological remission have more favorable outcomes than those with active histological disease in ulcerative colitis.

Graphical abstract Biologic and new small molecule therapies have been shown to be effective in treating patients with moderate to severe inflammatory bowel disease (IBD), both Crohn’s disease and ulcerative colitis. The risk of major adverse cardiovascular events (MACE), such as heart attack or heart failure, due to taking these medications in patients with IBD is not well established. The aim of this systematic review and meta-analysis is to estimate the risk of MACE in patient with IBD on biologic or small molecule therapies during induction and maintenance phases of randomized controlled trials.