The paradigm for treatment for ulcerative colitis (UC) is shifting from resolving symptoms toward objective measures such as mucosal healing (MH). However, it is unclear whether MH is associated with ...improved long-term outcomes. We performed a systematic review and meta-analysis to identify and analyze studies comparing long-term outcomes of patients with MH with those without MH.
We performed a systematic search of 3 large databases to identify prospective studies of patients with active UC that included outcomes of patients found to have MH at the first endoscopic evaluation after initiation of UC therapy (MH1) compared with those without MH1. The primary outcome was clinical remission after at least 52 weeks. Secondary outcomes included proportions of patients who were free of colectomy or corticosteroids and rate of MH after at least 52 weeks.
We analyzed 13 studies comprising 2073 patients with active UC. Patients with MH1 had pooled odds ratio of 4.50 for achieving long-term (after at least 52 weeks) clinical remission (95% confidence interval CI, 2.12-9.52), 4.15 for remaining free of colectomy (95% CI, 2.53-6.81), 8.40 for achieving long-term MH (95% CI, 3.13-22.53), and 9.70 for achieving long-term corticosteroid-free clinical remission (95% CI, 0.94-99.67), compared with patients without MH1. We found no difference in outcomes if patients achieved MH1 while receiving biologic versus non-biologic therapy.
In a meta-analysis, we associated MH with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission. MH is therefore appropriate goal of UC therapy.
Tumor necrosis factor-α (TNFα) antagonists have advanced the management of inflammatory bowel diseases patients leading to an improvement of patient's quality of life with the reduction of number of ...surgeries and hospitalizations. Despite these advances, many patients do not respond to the induction therapy (primary non-response-PNR) or lose response during the treatment (secondary loss of response-LOR). In this paper we will provide an overview of the definition, epidemiology and risk factors for PNR and LOR, as well as discuss the therapeutic options for managing LOR.
Changes in the colonic microbiota may play a role in the pathogenesis of ulcerative colitis (UC) and restoration of healthy gut microbiota may ameliorate disease. A systematic review and ...meta-analysis was conducted to assess fecal microbiota transplantation (FMT) as a treatment for active UC.
A literature search was conducted to identify high-quality studies of FMT as a treatment for patients with UC. The primary outcome was combined clinical remission and endoscopic remission or response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Odds ratios with 95% confidence intervals (CIs) are reported.
Overall, 4 studies with 277 participants were eligible for inclusion. Among 4 randomized controlled trials, FMT was associated with higher combined clinical and endoscopic remission compared with placebo (risk ratio UC not in remission was 0.80; 95% CI: 0.71-0.89) with a number needed to treat of 5 (95% CI: 4-10). There was no statistically significant increase in serious adverse events with FMT compared with controls (risk ratio adverse event was 1.4; 95% CI: 0.55-3.58).
Among randomized controlled trials, short-term use of FMT shows promise as a treatment to induce remission in active UC based on the efficacy and safety observed. However, there remain many unanswered questions that require further research before FMT can be considered for use in clinical practice.
Patients with cirrhosis who develop spontaneous bacterial peritonitis (SBP) have been reported to experience a high incidence of renal impairment and mortality. Renal dysfunction is possibly related ...to altered systemic hemodynamics that leads to decreased effective arterial blood volume. Albumin, a plasma volume expander, has been investigated to determine whether it plays a role in patients with SBP. The current literature suggests that albumin can reduce renal impairment and mortality in high-risk SBP patients, defined as patients with a serum bilirubin level of greater than 68.4 μmol⁄L, a blood urea nitrogen level of greater than 10.7 mmol⁄L or a serum creatinine level greater than 88.4 μmol⁄L. The rationale for albumin and other volume expanders in SBP is discussed, accompanied by a review of the current literature.
Abstract
Background
High histologic remission rates have been reported with placebos in randomized controlled trials (RCTs) evaluating ulcerative colitis (UC) therapies and have varied based on trial ...designs. We performed a systematic review and meta-analysis to quantify placebo histological remission rates and identify factors influencing those rates.
Methods
MEDLINE, EMBASE, and the Cochrane library were searched from inception of the databases until December 2021. We included placebo-controlled RCTs of adult patients with UC treated with aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. We pooled estimates using a random-effects model and performed subgroup analysis and meta-regression to evaluate the effect of different covariates on placebo rates.
Results
Thirty-three studies (30 induction and 3 maintenance) were included. The overall placebo histological remission rate was 15.7% (95% confidence interval, 12.9%-19%) across all 33 studies. High heterogeneity was observed among studies with I2 = 62.10%. The pooled estimate of histological remission was 15.8% in induction studies and 14.5% in maintenance studies. Subgroup analysis revealed statistically significant differences in placebo rates when accounting for background medications, the intervention drug class, and disease severity (P = .041, .025, and .025, respectively). There was no statistical difference between induction vs maintenance studies or between different histological scales (P = .771, and .075, respectively).
Conclusions
Placebo histological remission rates range from 13% to 19% in UC RCTs, but studies are highly heterogeneous. Factors found to influence placebo rates include presence of background medications, the drug used, and the disease severity. These observations inform future trial designs to minimize placebo rates and reduce heterogeneity.
Lay Summary
High histological remission rates have been reported with placebos in ulcerative colitis randomized control trials. This review aims to quantify placebo histological remission rates and identify factors influencing those rates to improve future trial designs.
Crohn's disease (CD) is an idiopathic inflammatory bowel disease and has no known cure. CD symptoms are treated using an array of medicines, including biological agents such as infliximab. However, ...infliximab therapy is expensive; therefore, identifying variables that can help predict response to infliximab is worthwhile. The present article reviews the impact of tobacco smoking on the efficacy of infliximab in CD. Earlier studies have speculated that smoking has a negative effect on the response to infliximab in CD, but the current literature is largely unable to identify a significant relationship between the two. Although smoking is known to have a negative effect on the course of CD, as well as other organ systems, presently, a CD patient's smoking status should not influence treatment decisions regarding infliximab therapy.
Aim
To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn’s disease (CD).
Methods
This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 ...at 10,000 IU daily (
n
= 18) compared to 1000 IU daily (
n
= 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores.
Results
High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L standard deviation (SD) 11.7 nmol/L to 160.8 nmol/L (SD 43.2 nmol/L) (
p
= 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%,
p
= 0.0844). In per-protocol analysis, clinical relapse of Crohn’s disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (
p
= 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3.
Conclusions
Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted.
Clinicaltrials.gov registration no
NCT02615288.
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