Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir with low-dose ribavirin in patients with chronic hepatitis C virus genotype 1a infection without cirrhosis.

Patients infected with hepatitis C virus (HCV) treated with interferon-free direct-acting antivirals may still require ribavirin. However, ribavirin is associated with adverse events that can limit its use. This open-label, multicentre, Phase 3 study evaluated the safety and efficacy of ombitasvir/paritaprevir/ritonavir + dasabuvir (OBV/PTV/r + DSV) with low-dose ribavirin for 12 weeks in genotype 1a-infected patients without cirrhosis. The primary efficacy endpoint was sustained virologic response at post-treatment Week 12 (SVR12). The primary safety endpoint was haemoglobin <10 g/dL during treatment and decreased from baseline. Overall, 105 patients enrolled. The SVR12 rate was 89.5% (n/N = 94/105; 95% CI, 83.7-95.4). The study did not achieve noninferiority versus the historic SVR12 rate for OBV/PTV/r + DSV plus weight-based ribavirin. Five patients experienced virologic failure, four discontinued, and two had missing SVR12 data. Excluding nonvirologic failures, the SVR12 rate was 94.9% (n/N = 94/99). One patient met the primary safety endpoint. OBV/PTV/r + DSV plus low-dose ribavirin offers an alternative option for patients in whom full-dose ribavirin may compromise tolerability, although noninferiority to the weight-based ribavirin regimen was not met.

Once-daily Mesalamine Formulation for Maintenance of Remission in Ulcerative Colitis: A Randomized, Placebo-controlled Clinical Trial.

GOALS: To evaluate the efficacy and safety of mesalamine granules 1.5 g once daily for maintenance of ulcerative colitis (UC) remission. BACKGROUND: Mesalamine is a first-line treatment for induction and maintenance of UC remission. STUDY: A phase 3, randomized, double-blind, placebo-controlled trial of patients with a history of mild to moderate UC, currently in remission, who received mesalamine granules once daily for 6 months. The primary efficacy endpoint was percentage of patients maintaining UC remission at 6 months. RESULTS: A significantly greater percentage of patients receiving mesalamine granules versus placebo were in remission at 6 months (79.9% vs. 66.7%; P=0.03). A greater percentage of patients receiving mesalamine granules maintained a revised Sutherland Disease Activity Index (SDAI)≤2 with no individual component of revised SDAI>1 and rectal bleeding=0 at 6 months (72.0% vs. 58.1%; P=0.04). No significant differences between groups were observed for change from baseline to 6 months for total SDAI score or its components (ie, stool frequency, rectal bleeding, mucosal appearance, physician's rating of disease). Mesalamine granules treatment resulted in a significantly longer remission duration versus placebo (P=0.02) and decreased patients' risk of relapse by 43% (hazard ratio=0.57; 95% confidence interval, 0.35-0.93; P=0.02). Mesalamine granules were well tolerated, and adverse events related to hepatic, renal, and pancreatic function-potential concerns with long-term treatment-occurred at a rate similar to placebo. CONCLUSIONS: Once-daily mesalamine granules are efficacious and safe for the maintenance of UC remission.

Long-Term Benefit of Mesalamine Granules for Patients Who Achieved Corticosteroid-Induced Ulcerative Colitis Remission.

BACKGROUND: Patients with ulcerative colitis (UC) who achieve remission with corticosteroids often relapse after tapering or discontinuation; alternative treatments limiting steroid exposure and UC relapse would be beneficial. It remains uncertain whether patients with corticosteroid-induced remission experience benefit with mesalamine granules (MG), a locally acting aminosalicylate extended-release capsule formulation for maintenance of UC remission in adults. AIMS: Efficacy and safety of MG 1.5 g once daily was evaluated in patients with UC in corticosteroid-induced remission. METHODS: Data from patients with previous corticosteroid use to achieve baseline UC remission were analyzed from two 6-month randomized, double-blind, placebo-controlled trials and a 24-month open-label extension (OLE). Six-month relapse-free rates were assessed using the revised Sutherland Disease Activity Index. UC-related adverse events (AEs) were recorded during the 30 months. RESULTS: Included were 158 steroid-treated patients in UC remission (MG, n = 105; placebo, n = 53) and 74/105 MG-treated patients who continued MG in the OLE. A significantly larger percentage of patients remained relapse-free at 6 months with MG (77.1 %) versus placebo (54.7 %; P = 0.006), with a 55 % reduction in relapse risk (hazard ratio [HR] 0.45; 95 % CI 0.25-0.79). There was a similar (49.2 %) reduction in risk of UC-related AEs at 6 months (HR 0.51; 95 % CI 0.31-0.84; P = 0.009) that was sustained during the OLE. CONCLUSIONS: MG 1.5 g once daily administered for maintenance of corticosteroid-induced remission was associated with low risk of relapse and UC-related AEs. CLINICALTRIALS.GOV: NCT00744016, NCT00767728, and NCT00326209.

An open label, non-randomized study assessing a prebiotic fiber intervention in a small cohort of Parkinson's disease participants.

A pro-inflammatory intestinal microbiome is characteristic of Parkinson's disease (PD). Prebiotic fibers change the microbiome and this study sought to understand the utility of prebiotic fibers for use in PD patients. The first experiments demonstrate that fermentation of PD patient stool with prebiotic fibers increased the production of beneficial metabolites (short chain fatty acids, SCFA) and changed the microbiota demonstrating the capacity of PD microbiota to respond favorably to prebiotics. Subsequently, an open-label, non-randomized study was conducted in newly diagnosed, non-medicated (n = 10) and treated PD participants (n = 10) wherein the impact of 10 days of prebiotic intervention was evaluated. Outcomes demonstrate that the prebiotic intervention was well tolerated (primary outcome) and safe (secondary outcome) in PD participants and was associated with beneficial biological changes in the microbiota, SCFA, inflammation, and neurofilament light chain. Exploratory analyses indicate effects on clinically relevant outcomes. This proof-of-concept study offers the scientific rationale for placebo-controlled trials using prebiotic fibers in PD patients. ClinicalTrials.gov Identifier: NCT04512599.

The Plicator procedure for the treatment of gastroesophageal reflux disease: a registry study.

BACKGROUND: Endoscopic full-thickness plication of the gastric cardia using the Plicator is shown to be effective for the treatment of symptomatic gastroesophageal reflux disease (GERD) in both prospective and randomized controlled trials. This registry study aimed to evaluate Plicator procedure safety and efficacy among GERD patients treated in routine clinical practice at multiple academic and nonacademic centers. METHODS: An open-label, prospective multicenter trial was conducted at seven centers under institutional review board approval. Patients with symptomatic GERD completed a series of questionnaires at baseline to assess GERD symptoms, heartburn/regurgitation scores, antisecretory medication use, and treatment satisfaction. All the patients then underwent the Plicator procedure with placement of a single transmural pledgeted suture in the anterior gastric cardia. The patients were reevaluated at 12 months after plication. RESULTS: The 12-month follow-up assessment was completed by 81 patients. At 12 months, the mean GERD Health-Related Quality-of-Life score had improved significantly compared with the baseline score (12.0 vs 26.6; p < 0.001), with 66% of the subjects showing an GERD-HRQL score improved 50% or more. Statistically significant improvements also were observed in median heartburn and regurgitation symptom scores. At 12 months, the need for daily proton pump inhibitor (PPI) therapy was eliminated for 58% of the patients. At baseline, 18% of the subjects had been satisfied with their GERD symptom control while on antisecretory therapy. At 12 months, 75% of the patients were satisfied with their GERD symptom control after undergoing the Plicator procedure, and 86% would recommend the procedure to family or friends. There were no serious adverse events and no late onset of any adverse events. CONCLUSIONS: In this multicenter study, the Plicator procedure effectively improved GERD quality-of-life scores, reduced GERD symptoms and medication use, and yielded higher treatment satisfaction than with the use of chronic antisecretory therapy. These effects all were seen 12 months after plication, and no major adverse effects were observed.

Increasing efficacy and reducing side effects in treatment of chronic anal fissures: A study of topical diazepam therapy.

This is a single institution nonexperimental study intended to analyze the therapeutic efficacy of topical diazepam in treating symptoms of chronic anal fissures.Anal fissures are a common cause of anal pain. Conventional treatments include nonsteroidal anti-inflammatory drugs, topical creams, such as nitroglycerin and nifedipine, and surgery. However, these treatments are usually suboptimally efficacious or have deterring side effects.Patients at an outpatient community center with a diagnosis of a chronic anal fissure were prescribed either topical 2% (n = 19) or 4% (n = 18) diazepam cream between January 2013 and February 2015. We retrospectively analyzed their responses to treatment.All 19 patients using 2% diazepam cream experienced a positive response in pain, whereas 47.4% experienced a complete response, with a numerical rating scale (NRS) score of 0 (0-10). Eighty-eight percent of patients using 4% dose had a positive response in pain, whereas 23.5% experienced a complete response. Ninety-four percent of patients using 2% dose had a positive response in anal bleeding, whereas 68.8% experienced a complete response with an anal bleeding score (ABS) of 2 (2-9). Ninety-four percent of patients using 4% dose had a positive response in anal bleeding, whereas 64.7% experienced a complete response. Only 1 patient reported a side effect from diazepam cream-perianal pruritus.Both 2% and 4% topical diazepam provided significant pain and bleeding relief from chronic anal fissures that were refractory to conventional therapies. There were insignificant differences when assessing independent comparisons for pain and bleeding between the doses.

Once-daily mesalamine granules for maintaining remission of ulcerative colitis: pooled analysis of efficacy, safety, and prognostic factors.

OBJECTIVES: A capsule formulation of mesalamine granules (MG) was developed for once-daily dosing and better compliance. The study aim was to evaluate MG efficacy and tolerability in maintaining ulcerative colitis (UC) remission. METHODS: Pooled analysis of 2 identical phase 3, randomized, double-blind trials of once-daily MG 1.5 g or placebo for up to 6 months. The primary endpoint was percentage of patients remaining relapse-free at month 6 versus placebo. Relapse was defined as revised Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, UC flare, or UC-related adverse event (AE). RESULTS: Data were pooled for patients receiving MG (n = 373) and placebo (n = 189). Significantly more patients were relapse-free at 6 months with MG (79.4%) than placebo (62.4%; P < 0.001) and across subgroups based on select demographic and baseline characteristics (P < 0.05). Secondary outcome measures including rectal bleeding, physician rating of disease activity, stool frequency, total SDAI score, and relapse-free duration favored MG (P < 0.01). Common AEs with MG and placebo, respectively, were headache (10.9% and 7.6%), diarrhea (7.9% and 7.0%), and abdominal pain (6.3% and 6.5%). CONCLUSION: Once-daily MG was more efficacious than and as well tolerated as placebo in maintaining UC remission. ClinicalTrials.gov identifiers: NCT00744016 and NCT00767728.

Briakinumab for treatment of Crohn's disease: results of a randomized trial.

BACKGROUND: This study assessed the efficacy and safety of briakinumab, a human anti-IL-12/23p40 monoclonal antibody, compared with placebo for the induction and maintenance of remission in patients with moderately to severely active Crohn's disease. METHODS: In this phase 2b, multicenter, double-blind, parallel group study, 246 patients stratified by prior tumor necrosis factor-antagonist use and response, were randomized (1:1:1:3) to 4 intravenous induction regimens: placebo, 200, 400, or 700 mg briakinumab, at weeks 0/4/8. At week 12, responders in the placebo or 400-mg induction groups entered the maintenance phase with the same regimen, whereas responders in the 700-mg induction group were rerandomized (1:1:1) to receive placebo, 200, or 700 mg briakinumab at weeks 12/16/20. At week 24, patients in remission stopped receiving study drug (withdrawal phase) until relapse. Patients experiencing relapse, nonresponders, and nonremitters could enter the open-label phase. RESULTS: The primary end point of clinical remission at week 6 was not met. There were numerically greater rates of remission and response at 6, 12, or 24 weeks in patients treated with briakinumab. The safety and tolerability profile of briakinumab was similar in the induction and maintenance phases of the trial. CONCLUSIONS: Briakinumab showed a similar safety and tolerability profile to placebo in the induction and maintenance phases, and comparable rates of serious adverse events, adverse events leading to discontinuation, and malignancy. These data provide support for the potential efficacy of briakinumab and other IL-12/23 inhibitors in the treatment of moderate-to-severe Crohn's disease.

Pattern of alcohol consumption and its effect on gastrointestinal symptoms in inflammatory bowel disease.

Alcohol consumption is a potential trigger for flare in inflammatory bowel disease (IBD) flare because of alcohol's pro-oxidant effects and its deleterious effects on gut barrier function. The association with alcohol consumption and IBD flare is unclear. To test this hypothesis, we evaluated the pattern of alcohol consumption and its self-reported effect on gastrointestinal (GI) symptoms in patients with IBD. We recruited 129 consecutive patients: 52 patients with Crohn's disease, 38 patients with ulcerative colitis, and 39 patients with irritable bowel syndrome (IBS). All the participants completed a validated questionnaire on disease activity (the Crohn's disease activity index or ulcerative colitis clinical activity index, respectively) validated questionnaires to quantify alcohol consumption by National Institute of Alcohol Abuse and Alcoholism criteria, and two structured questionnaires we designed to access patients' perception of the effect of alcohol on their GI symptoms and on overall GI symptom severity. The pattern of current, light, moderate, and heavy alcohol consumption in inactive IBD was similar to the general U.S. population. Specifically, of the 90 inactive IBD patients, 56 (62%) were current drinkers, compared with 61% in the general U.S. population. Of current drinkers, 75% of IBD (N=42) and 43% of IBS (N=9) reported a worsening of GI symptoms with alcohol consumption (P=.01); however, overall GI symptom severity did not differ when compared with quantity of alcohol consumed. Patients with inactive IBD drink alcohol in quantities similar to the general population. Current drinkers with inactive IBD are more likely to report worsening of GI symptoms with alcohol than current drinkers with IBS.

Endoluminal full-thickness plication and radiofrequency treatments for GERD: an outcomes comparison.

HYPOTHESIS: Endoluminal therapies have emerged as adjuncts for the treatment of gastroesophageal reflux disease (GERD) in select patients. OBJECTIVE: To compare the effectiveness of endoscopic full-thickness plication and endoscopic radiofrequency treatments for patients with GERD. PATIENTS: A total of 126 patients who underwent either endoscopic full-thickness plication (FTP) of the gastric cardia or endoscopic radiofrequency (RF) treatment of the esophagogastric junction during a 4-year period were included (68 underwent RF and 58 underwent FTP). INTERVENTIONS: Follow-up data was obtained for 51% of patients (mean follow-up, 6 months). MAIN OUTCOME MEASURES: Comparison of medication use, symptom scores, and pH values at baseline and follow-up. RESULTS: In the RF group, patients with moderate to severe heartburn decreased from 55% to 22% (P < .01), and proton pump inhibitor (PPI) use decreased from 84% to 50% (P = .01). Decreases were also seen for dysphagia, voice symptoms, and cough. Percentage of time the pH was less than 4 was unchanged. In the FTP group, patients with moderate to severe heartburn decreased from 53% to 43% (P = .3), and PPI use decreased from 95% to 43% (P = .01). Percentage of time the pH was less than 4 decreased from 10.0% to 6.1% (P = .05). Decreases were also seen for regurgitation, voice symptoms, and dysphagia. There was no change in scores for chest pain or asthma in either group. CONCLUSIONS: For patients with GERD, RF and FTP both resulted in a decrease in both PPI use and in scores for voice symptoms and dysphagia. In addition, RF resulted in decreased heartburn and cough, while FTP resulted in the most dramatic reduction in regurgitation. Our experience indicates that both procedures are effective, providing symptomatic relief and reduction in PPI use. For patients whose chief complaint is regurgitation, FTP may be the preferred procedure.

Impact of sleep disturbances in inflammatory bowel disease.

BACKGROUND: Normal sleep is paramount for a healthy lifestyle and high quality of life. Sleep modulates the immune system and thus affects the course of several chronic inflammatory conditions. There are no reported studies that address the role of sleep disturbance in the course of inflammatory bowel disease (IBD). The aim of this study was to characterize sleep disturbance in IBD using validated measures of sleep and quality of life. METHODS: A self-administered, mail-in questionnaire package was sent to 205 subjects after a brief instruction. The questionnaire package was composed of the Pittsburgh Sleep Quality Index (PSQI), a measure of disease severity and the IBD-Quality of Life Questionnaire. A total of 119 subjects were recruited (58% response rate): 80 with inactive IBD, 24 with irritable bowel syndrome (IBS) and 15 healthy controls. RESULTS: The IBD subjects reported significantly prolonged sleep latency, frequent sleep fragmentation, higher rate of using sleeping pills, decreased day-time energy, increased tiredness and poor overall sleep quality compared to healthy controls. The abnormal sleep patterns in IBD subjects were similar to IBS subjects. The reported sleep quality was correlated with IBD disease severity score (r(2) = 0.55, P = 0.02). Both IBD and IBS subjects thought that sleep and their disease status were correlated. CONCLUSION: The results show that IBD patients have significant sleep disturbance even when their disease is not active. This problem might affect quality of life, gastrointestinal symptoms and coping ability, and might potentially modify disease severity or increase risk of flare-up. Regardless of the primary or secondary origin of this problem, sleep disturbance should be addressed in the clinical management of patients with IBD.