Remimazolam can be administered safely under the supervision of endoscopists for outpatient colonoscopy, and it allows faster recovery of neuropsychiatric function compared with placebo (midazolam rescue) and midazolam. (Clinical trial registration number: NCT02290873.).

In patients with chronic constipation, lubiprostone produced a bowel movement in the majority of individuals within 24 h of initial dosing, with sustained improvement in frequency as well as other constipation symptoms over 4 weeks of treatment.

No abstract

Two 750-mg FCM infusions are safe and superior to oral iron in increasing Hb levels in IDA patients with inadequate oral iron response.

SUMMARY Background Gluten-free diet (GFD) is the only management available for celiac disease (CeD), a permanent immune intolerance to gluten. Nexvax2® is the first therapeutic vaccine designed to treat CeD. The adjuvant-free formulation of peptides is intended to engage and render gluten-specific CD4+ T cells unresponsive to further antigenic stimulation. We have assessed safety and pharmacodynamics of Nexvax2® in patients with CeD on GFD. Methods In two randomized, double-blind, placebo-controlled, phase 1 studies at 12 community sites in Australia, New Zealand and the United States, we screened for HLA-DQ2·5+ CeD patients (aged 18–70 years) on GFD. The screening and post-treatment periods included either a crossover, placebo-controlled, oral gluten challenge (OGC) to mobilize and assess T cells responsive to Nexvax2 or, for the final cohort in each study, endoscopy and duodenal histology without OGC. Participants and study staff were masked to the gluten content of food provided for each interval of the OGCs. One of two sequences of active and placebo challenges was assigned (1:1) by central randomization using a simple block method. The sequence of challenges was active/placebo then active/placebo, or placebo/active then active/placebo for the OGCs in the screening and post-treatment periods, respectively. Participants with a negative interferon (IFN)-γ release assay (IGRA) to Nexvax2 peptides after the screening OGC, or Marsh score >1 were discontinued before dosing. There was temporal allocation of participants to sequential cohorts assessing multiple fixed intradermal doses of Nexvax2 (60µg, 90µg, or 150µg weekly in the 3-dose study; or 150µg, or 300µg two-times weekly in the 16-dose study) in 0.1 mL 0.9% sodium chloride. A maximum tolerated dose (MTD) was administered in the final biopsy cohort in each study. Participants within each cohort were assigned to receive Nexvax2 or placebo by central randomization (2:1, respectively) using simple block method in SAS software Version 9·2. Participants, investigators, and study staff were masked to the treatment assignment, except for the study pharmacist. The primary endpoint was the number and percentage of adverse events in the treatment period. Other safety outcomes included duodenal histology, gastrointestinal symptoms, plasma cytokines, and immune cell frequencies. The main pharmacodynamic endpoint was IGRA to Nexvax2 peptides. All participants who received Nexvax2 or placebo, the safety population, were included in an intention to treat analysis for the primary endpoint. Additional post hoc analyses were also performed. Both trials were completed and closed before data analysis. Trials were registered with Australian New Zealand Clinical Trials Registry, numbers ACTRN12612000355875 and ACTRN12613001331729. Findings Participants were screened from November 28, 2012 to August 14, 2014, and August 3, 2012 to September 10, 2013, for the 3-dose and 16-dose studies respectively. Across both studies, 136 (80%) of 169 volunteers met initial eligibility crite...

The combination of natalizumab plus infliximab was well tolerated. Several positive trends suggested that treating patients not in remission with infliximab plus natalizumab had greater efficacy than treatment with infliximab alone.

Nonalcoholic steatohepatitis, a chronic liver disease without an approved therapy, is associated with lipotoxicity and insulin resistance and is a major cause of cirrhosis and hepatocellular carcinoma.Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial. ARREST, a 52-week, doubleblind, placebo-controlled, phase 2b trial randomized 247 non-alcoholic steatohepatitis (NASH) patients (101, 98, 48 in aramchol 400mg, 600mg, placebo, respectively; NCT 02279524). The primary endpoint was a decrease in hepatic triglycerides by magnetic resonance spectroscopy at 52 weeks with a dose of 600 mg of aramchol. Key secondary endpoints included liver histology and ALT. Aramchol 600 mg produced a placebo-corrected decrease in liver triglycerides without meeting the prespecified significance (-3.1, 95%CI -6.4 to 0.2, p=0.06), precluding further formal statistical analysis. NASH resolution without worsening fibrosis was achieved in 16.7% (13/78) of aramchol 600 mg versus 5% (2/40) of the placebo arm (OR=4.74, 95% CI:0.1-22.7) and fibrosis improvement Vlad Ratziu, Study Design, Patient Recruitment and Treatment, Data Analyses and Interpretation, member of study advisory committee, Manuscript Writing

Background: Interleukin‐11 is a mesenchymally derived cytokine with pleiotropic activities. A pilot study suggested therapeutic benefit of recombinant human interleukin‐11 (rhIL‐11) in patients with Crohn's disease. Aim: To determine the safety and preliminary estimate of efficacy of rhIL‐11 in treating active Crohn's disease. Methods: Patients with mild to moderately active Crohn's disease, defined as a Crohn's disease activity index (CDAI) ≥ 220 and ≤ 450, were enrolled in a multicentre trial. Stable doses of 5‐aminosalicylates, antibiotics, 6‐mercaptopurine or azathioprine were permitted with appropriate wash‐in periods. Oral, intravenous or rectally administered corticosteroids were not allowed. Patients were randomized to 6 weeks of subcutaneous injection with rhIL‐11 15 μg/kg or placebo weekly, or rhIL‐11 7.5 μg/kg or placebo twice weekly. The primary end‐point was per cent change in CDAI at week 6; the major secondary end‐point was the proportion of patients in remission, defined as a 100 point decrease in CDAI and absolute CDAI ≤ 150. Results: Baseline characteristics were similar among the 148 evaluated patients (49 placebo, 49 rhIL‐11 15 μg/kg once weekly, 50 rhIL‐11 7.5 μg/kg twice weekly). Treatment was well‐tolerated, with mild injection site reactions occurring more frequently among patients treated with rhIL‐11. Headache, oedema, and increased platelet count occurred significantly more often in the rhIL‐11 7.5 μg/kg twice weekly group, but not the 15 μg/kg once weekly group. There was a trend toward decreased mean per cent change in CDAI in the rhIL‐11 15 μg/kg once weekly group vs. placebo (–31.5% vs. – 18.5%, 95% confidence interval for the difference – 27.9–1.6%). A significantly greater proportion of patients receiving rhIL‐11 15 μg/kg once weekly achieved remission compared to placebo (36.7% vs. 16.3%, 95% confidence interval for the difference 3.4–37.4%; 16.4% for rhIL‐11 7.5 μg/kg, N.S.). Conclusions: Weekly subcutaneous injection with rhIL‐11 15 μg/kg is safe and effective in inducing remission in a subset of patients with active Crohn's disease.