New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in ...perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort.
We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method.
Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively.
Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.
Mucosal healing (MH) is now considered as a major treatment goal in clinical trials and clinical practice for patients with inflammatory bowel disease (IBD). MH is associated with sustained clinical ...remission, steroid-free remission, and reduced rates of hospitalization and surgery. There is a well-known disconnect between clinical symptoms and mucosal lesions that is more pronounced in CD. More stringent therapeutic goals have been discussed recently such as deep remission defined as clinical remission associated with MH. Recent international guidelines from the IOIBD recommended deep remission as a treatment goal in clinical practice. However there is no validated definition of deep remission in IBD. Also, the efficacy of available drugs to induce and maintain deep remission in IBD is poorly known. Finally, whether deep remission is the best way to modify the course of IBD and whether it should be achieved before considering drug de-escalation have to be formally evaluated in upcoming disease-modification trials.
Cholera toxin (CT), a virulence factor elaborated by Vibrio cholerae, is sufficient to induce the severe diarrhea characteristic of cholera. The enzymatic moiety of CT (CtxA) increases cAMP synthesis ...in intestinal epithelial cells, leading to chloride ion (Cl−) efflux through the CFTR Cl− channel. To preserve electroneutrality and osmotic balance, sodium ions and water also flow into the intestinal lumen via a paracellular route. We find that CtxA-driven cAMP increase also inhibits Rab11/exocyst-mediated trafficking of host proteins including E-cadherin and Notch signaling components to cell-cell junctions in Drosophila, human intestinal epithelial cells, and ligated mouse ileal loops, thereby disrupting barrier function. Additionally, CtxA induces junctional damage, weight loss, and dye leakage in the Drosophila gut, contributing to lethality from live V. cholerae infection, all of which can be rescued by Rab11 overexpression. These barrier-disrupting effects of CtxA may act in parallel with Cl− secretion to drive the pathophysiology of cholera.
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•Cholera toxin disrupts Rab11/exocyst-mediated protein trafficking to cell junctions•Cholera toxin inhibits Notch signaling in Drosophila and in human intestinal cells•Elevating Rab11 rescues Ctx-induced weight loss and junctional defects in the gut•Elevating Rab11 rescues Ctx-dependent lethality of V. cholerae infection in flies
Mucosal healing (MH) has emerged as an important treatment goal for patients with IBD. Historically, the therapeutic goals of induction and maintenance of clinical remission seemed insufficient to ...change the natural history of IBD. Evidence has now accumulated to show that MH can alter the course of IBD, as it is associated with sustained clinical remission, and reduced rates of hospitalization and surgical resection. In patients with ulcerative colitis, MH may represent the ultimate therapeutic goal because inflammation is limited to the mucosa. In patients with Crohn's disease, which is a transmural disease, MH could be considered as a minimum therapeutic goal. This Review focuses on the definition of MH and discusses the ability of each available IBD medication to induce and maintain MH. The importance of achieving MH is also discussed and literature that demonstrates improvement of disease course with MH is reviewed. Finally, we discuss how best to integrate the treatment end point of MH into clinical practice for the management of patients with IBD.
Summary
Background
The prevalence of inflammatory bowel diseases (IBD) is high in women of childbearing age. Achieving clinical remission from conception to delivery using current medications is a ...major issue in IBD.
Aims
To assess maternal and neonatal complications and management of vedolizumab or ustekinumab) in pregnant women with IBD receiving these agents.
Methods
We performed a retrospective cohort study among GETAID centres including women with IBD who received ustekinumab or vedolizumab during pregnancy or within the 2 months before conception and compared outcomes to women exposed to anti‐TNF treatment during pregnancy.
Results
Seventy‐three pregnancies in 68 women with IBD were analysed: 29 on ustekinumab resulting in 26 (90%) live births, two (7%) spontaneous abortions and one (3%) elective termination; 44 on vedolizumab resulting in 38 (86%) live births, five (11%) spontaneous abortions and one (3%) medical interruption. The control group included 88 pregnancies exposed to anti‐TNF in 76 women with IBD. The median age at conception, the proportion of women who smoked or in clinical activity at conception was comparable between groups. Only the proportion of patients exposed to >2 anti‐TNF agents was significantly increased among the ustekinumab and vedolizumab groups compared to control group (22% and 10% vs 3%, P < 0.005). Rates of prematurity, spontaneous abortion, congenital malformations and maternal complications were comparable between groups.
Conclusion
We report 73 pregnancies in patients receiving vedolizumab or ustekinumab without a negative signal on maternal or neonatal outcomes. Further prospective studies are needed on the outcomes of pregnancies with new biologic drugs.
Summary
Background
Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate‐to‐severe ulcerative colitis (UC), but few real‐world data are currently available.
Aim
To ...assess short‐term effectiveness and safety of ustekinumab in patients with UC.
Methods
From January to September 2019, all patients with UC treated with ustekinumab in 20 French GETAID centres were retrospectively included. The primary outcome was steroid‐free clinical remission (partial Mayo Clinic score ≤2) at weeks 12‐16 without a rectal bleeding subscore >1.
Results
Among the 103 patients included, 70% had been previously exposed to ≥2 anti‐TNF agents and 85% to vedolizumab. At weeks 12‐16, steroid‐free clinical remission and clinical remission rates were 35.0% and 39.8% respectively; the absence of rectal bleeding with normal stool frequency was noted in 19.4% of patients. Two patients discontinued ustekinumab before the week 12‐16 visit and underwent surgery. In multivariable analysis, a partial Mayo Clinic score >6 at inclusion (18.6% vs 46.7%, P = 0.003) and a history of both exposure to anti‐TNF and vedolizumab therapies (27.3% vs 80.0%, P = 0.001) were negatively associated with steroid‐free clinical remission at weeks 12‐16. Adverse events occurred in 7.8% of patients and serious adverse events in 3.9% of patients.
Conclusion
In a cohort of highly refractory patients with UC with multiple prior drug failures, ustekinumab provided steroid‐free clinical remission in one‐third of cases at weeks 12‐16. Clinical severity and previous use of anti‐TNF and vedolizumab therapies were associated with ustekinumab failure at weeks 12‐16.
Summary
Background
Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real‐life long‐term data are currently available.
Aims
To assess the ...real‐world effectiveness and safety of ustekinumab in patients with UC.
Methods
From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score ≤2.
Results
We included 103 patients with UC (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) with an insufficient response to immunosuppressants, anti‐TNFs and/or vedolizumab. At week 52, 45 (44%) patients had discontinued ustekinumab mainly due to lack of effectiveness (n = 41). The cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7% and 58.4% after 3, 6, 9 and 12 months respectively. The overall steroid‐free clinical remission rate at week 52 was 32% of whom 71% had subscores of null for rectal bleeding and stool frequency. Ten patients underwent colectomy within a median of 6.7 4.3‐10.6 months. Adverse effects were observed in 15 (16.9%) patients; 4 (4.5%) were severe, including one patient who died from a myocardial infarction.
Conclusion
After 52 weeks, over one‐half of patients with refractory UC were still treated by ustekinumab and one‐third were in steroid‐free clinical remission.
Among 103 patients with ulcerative colitis treated with ustekinumab, one‐third achieved steroid‐free clinical remission and less than 10% were referred to surgery, after a 1‐year follow‐up period.
https://doi.org/10.1111/apt.16544
Natural history of eosinophilic gastroenteritis Pineton de Chambrun, Guillaume; Gonzalez, Florent; Canva, Jean-Yves ...
Clinical gastroenterology and hepatology,
11/2011, Letnik:
9, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Eosinophilic gastroenteritis (EGE) is a rare gastrointestinal disorder; little is known about its natural history. We determined the clinical features and long-term outcomes of patients with EGE.
We ...reviewed files from 43 patients diagnosed with EGE who were followed from January 1988 to April 2009. The diagnosis was made according to standard criteria after other eosinophilic gastrointestinal disorders were excluded. We analyzed data on initial clinical presentation and long-term outcomes.
EGE was classified as mucosal, subserosal, or muscular in 44%, 39%, and 12% of cases, respectively. Disease location was mostly duodenal (62%), ileal (72%), or colonic (88%); it was less frequently esophageal (30%) or gastric (38%). Blood eosinophilia (numbers >500/mm(3)) was observed in 74% of cases. Spontaneous remission occurred in 40% of patients; the majority of treated patients (74%) received oral corticosteroids, which were effective in most cases. After a median follow-up period of 13 years (0.8-29 years), we identified 3 different courses of disease progression: 18 patients (42%; 9 with subserosal disease) had an initial flare of the disease without relapse, 16 (37%) had multiple flares that were separated by periods of full remission (recurring disease), and 9 (21%) had chronic disease.
The clinical presentation of EGE is heterogeneous and varies in histologic pattern; about 40% of patients resolve the disease spontaneously, without relapse. Approximately 50% have a more complex disease, which is characterized by unpredictable relapses and a chronic course.
Background
Nearly 20% of patients who undergo hiatal hernia (HH) repair and anti-reflux surgery (ARS) report recurrent HH at long-term follow-up and may be candidates for redo surgery. Current ...literature on redo-ARS has limitations due to small sample sizes or single center experiences. This type of redo surgery is challenging due to rare but severe complications. Furthermore, the optimal technique for redo-ARS remains debatable. The purpose of the current multicenter study was to review the outcomes of redo-fundoplication and to identify the best ARS repair technique for recurrent HH and gastroesophageal reflux disease (GERD).
Methods
Data on 975 consecutive patients undergoing hiatal hernia and GERD repair were retrospectively collected in five European high-volume centers. Patient data included demographics, BMI, techniques of the first and redo surgeries (mesh/type of ARS), perioperative morbidity, perioperative complications, duration of hospitalization, time to recurrence, and follow-up. We analyzed the independent risk factors associated with recurrent symptoms and complications during the last ARS. Statistical analysis was performed using GraphPad Prism
®
and R software
®
.
Results
Seventy-three (7.49%) patients underwent redo-ARS during the last decade; 71 (98%) of the surgeries were performed using a minimally invasive approach. Forty-two (57.5%) had conversion from Nissen to Toupet. In 17 (23.3%) patients, the initial Nissen fundoplication was conserved. The initial Toupet fundoplication was conserved in 9 (12.3%) patients, and 5 (6.9%) had conversion of Toupet to Nissen. Out of the 73 patients, 10 (13%) underwent more than one redo-ARS. At 8.5 (1–107) months of follow-up, patients who underwent reoperation with Toupet ARS were less symptomatic during the postoperative period compared to those who underwent Nissen fundoplication (
p
= 0.005, OR 0.038). Patients undergoing mesh repair during the redo-fundoplication (21%) were less symptomatic during the postoperative period (
p
= 0.020, OR 0.010). The overall rate of complications (Clavien-Dindo classification) after redo surgery was 11%. Multivariate analysis showed that the open approach (
p
= 0.036, OR 1.721), drain placement (
p
= 0.0388, OR 9.308), recurrence of dysphagia (
p
= 0.049, OR 8.411), and patient age (
p
= 0.0619, OR 1.111) were independent risk factors for complications during the last ARS.
Conclusions
Failure of ARS rarely occurs in the hands of experienced surgeons. Redo-ARS is feasible using a minimally invasive approach. According to our study, in terms of recurrence of symptoms, Toupet fundoplication is a superior ARS technique compared to Nissen for redo-fundoplication. Therefore, Toupet fundoplication should be considered in redo interventions for patients who initially underwent ARS with Nissen fundoplication. Furthermore, mesh repair in reoperations has a positive impact on reducing the recurrence of symptoms postoperatively.
Abstract Background We aimed to evaluate clinical symptoms in subjects with irritable bowel syndrome receiving Saccharomyces cerevisiae in a randomized double-blind placebo-controlled clinical trial. ...Methods Overall, 179 adults with irritable bowel syndrome (Rome III criteria) were randomized to receive once daily 500 mg of Saccharomyces cerevisiae , delivered by one capsule ( n = 86, F: 84%, age: 42.5 ± 12.5), or placebo ( n = 93, F: 88%, age: 45.4 ± 14) for 8 weeks followed by a 3-week washout period. After a 2-week run-in period, cardinal symptoms (abdominal pain/discomfort, bloating/distension, bowel movement difficulty) and changes in stool frequency and consistency were recorded daily and assessed each week. A safety assessment was carried out throughout the study. Results The proportion of responders, defined by an improvement of abdominal pain/discomfort, was significantly higher ( p = 0.04) in the treated group than the placebo group (63% vs 47%, OR = 1.88, 95%, CI: 0.99–3.57) in the last 4 weeks of treatment. A non-significant trend of improvement was observed with Saccharomyces cerevisiae for the other symptoms. Saccharomyces cerevisiae was well tolerated and did not affect stool frequency and consistency. Conclusion Saccharomyces cerevisiae is well tolerated and reduces abdominal pain/discomfort scores without stool modification. Thus, Saccharomyces cerevisiae may be a new promising candidate for improving abdominal pain in subjects with irritable bowel syndrome.
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