Asthma-Related Outcomes in Patients Initiating Extrafine Ciclesonide or Fine-Particle Inhaled Corticosteroids.

Purpose: Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone).

Methods: This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS.

Efficacy and safety of fixed-dose combination therapy, alogliptin plus metformin, in Asian patients with type 2 diabetes: A phase 3 trial.

This study evaluated the efficacy and safety of 26 weeks of twice-daily (BID) alogliptin + metformin fixed-dose combination (FDC) therapy in Asian patients with type 2 diabetes. Patients aged 18 to 75 years with hemoglobin A1c (HbA1c) of 7.5% to 10.

Efficacy and Safety of Vedolizumab in Ulcerative Colitis and Crohn's Disease Patients Stratified by Age.

Introduction: The efficacy and safety of vedolizumab, a gut-selective αβ integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18-80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials.

Methods: Safety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years.

Managing glycaemia in older people with type 2 diabetes: A retrospective, primary care-based cohort study, with economic assessment of patient outcomes.

Aims: To describe the relative health and economic outcomes associated with different second-line therapeutic approaches to manage glycaemia in older type 2 diabetes patients requiring escalation from metformin monotherapy.

Materials And Methods: The Clinical Practice Research Datalink database was used to inform a retrospective observational cohort study of patients with type 2 diabetes treated with metformin monotherapy requiring escalation (addition or switch) to a second-line oral regimen from January 1, 2008 to December 31, 2014. Primary outcomes included time to first event (any event, myocardial infarction [MI], stroke, or composite of MI/stroke [major adverse cardiovascular event; MACE]) and total event rate.

Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease in Patients Naïve to or Who Have Failed Tumor Necrosis Factor Antagonist Therapy.

Background: Vedolizumab is a gut-selective α4β7 integrin antagonist for the treatment of moderately to severely active Crohn's disease (CD). Aims of this study were to characterize the efficacy and safety of vedolizumab induction and maintenance therapy in patients who were naïve to tumor necrosis factor-alpha (TNF-α) antagonist therapy (TNF-naïve) or who had discontinued TNF-α antagonist therapy because of inadequate response (i.e.

Effect of Multiple Oral Doses of the Potent CYP3A4 Inhibitor Clarithromycin on the Pharmacokinetics of a Single Oral Dose of Vonoprazan: A Phase I, Open-Label, Sequential Design Study.

Background And Objectives: This phase I, open-label, sequential design study assessed the effect of multiple oral doses of the potent cytochrome P450 (CYP) 3A4 inhibitor clarithromycin on the pharmacokinetics of a single oral dose of vonoprazan.

Methods: During the 10-day treatment period, 16 healthy male subjects received vonoprazan 40 mg on days 1 and 8, and clarithromycin 1000 mg on days 3-9, with the pharmacokinetics of both examined. Primary endpoints included the maximum observed plasma concentration (C ) and area under the plasma concentration-time curve (AUC) of vonoprazan and its major metabolites (M-I, M-II, M-III, and M-IV-Sul).

Effects of vedolizumab on health-related quality of life in patients with ulcerative colitis: results from the randomised GEMINI 1 trial.

Background: Health-related quality of life (HRQL) is often diminished in patients with ulcerative colitis.

Aim: To evaluate the effects of vedolizumab on HRQL in patients with ulcerative colitis.

Methods: Using maintenance phase data from the GEMINI 1 study, an analysis of covariance model was used to calculate mean differences between the vedolizumab and placebo groups in changes from baseline to week 52 for 3 HRQL instruments: The Inflammatory Bowel Disease Questionnaire (IBDQ), 36-Item Short Form Health Survey (SF-36), and EQ-5D.

The Cost-Effectiveness of Alogliptin Versus Sulfonylurea as Add-on Therapy to Metformin in Patients with Uncontrolled Type 2 Diabetes Mellitus.

Introduction: ENDURE (ClinicalTrials.gov identifier, NCT00856284), a multicenter, double-blind, active-controlled study of 2639 patients with uncontrolled type 2 diabetes mellitus (T2DM), found that metformin in combination with alogliptin (12.5 and 25 mg doses), when compared to standard add-on therapy (sulfonylurea, SU), exerted sustained antihyperglycemic effects over 2 years.

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

Background: Biological therapies are increasingly used to treat ulcerative colitis (UC).

Aim: To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy.

Methods: A systematic literature review was undertaken to identify studies of biologics approved for UC.

Long-term Efficacy of Vedolizumab for Ulcerative Colitis.

Background And Aims: The GEMINI long-term safety [LTS] study is a continuing phase 3 trial investigating the safety and efficacy of vedolizumab, an α4β7 integrin antagonist for ulcerative colitis [UC] and Crohn's disease. We provide an interim analysis of efficacy in patients with UC.

Methods: Patients from the C13004 and GEMINI 1 studies and a cohort of vedolizumab-naïve patients received open-label vedolizumab every 4 weeks.

Long-term Efficacy of Vedolizumab for Crohn's Disease.

Background And Aims: Vedolizumab is a gut-selective α4β7 integrin antagonist therapy for ulcerative colitis and Crohn's disease. The GEMINI long-term safety [LTS] trial is an ongoing open-label study investigating the safety of vedolizumab. We present interim exploratory analyses of efficacy in patients with Crohn's disease.

Efficacy of Vedolizumab Induction and Maintenance Therapy in Patients With Ulcerative Colitis, Regardless of Prior Exposure to Tumor Necrosis Factor Antagonists.

Background & Aims: The efficacy and safety of vedolizumab, a humanized immunoglobulin G1 monoclonal antibody against the integrin α4β7, were demonstrated in multicenter, phase 3, randomized, placebo-controlled trials in patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease. We analyzed data from 1 of these trials to determine the effects of vedolizumab therapy in patients with UC, based on past exposure to anti-tumor necrosis factor-α (TNF) antagonists.

Methods: We performed a post hoc analysis of data from the GEMINI 1 study, collected from 464 patients who received vedolizumab or placebo but had not received a previous TNF antagonist (naive to TNF antagonists) and 367 patients with an inadequate response, loss of response, or intolerance to TNF antagonists (failure of TNF antagonists).

Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes: retrospective cohort study using datasets from four European countries.

Objective:  To evaluate the association between pioglitazone use and bladder cancer risk in patients with type 2 diabetes.

Design:  Retrospective cohort study using propensity score matched cohorts.

Settings:  Healthcare databases from Finland, the Netherlands, Sweden, and the United Kingdom.

Phase IV randomized preference study in patients eligible for calcium and vitamin D supplementation.

Introduction/objectives: Preference for supplement formulation helps determine an individual's adherence to long-term medication and can improve clinical benefit for chronic illnesses such as osteoporosis. This study compared the preference, acceptability and tolerability of a reformulation of Calcichew D3 500 mg/400 IU and Calcichew D3 500 mg/800 IU (Takeda UK Ltd, Wobrun Green, UK) with Adcal-D3 500 mg/400 IU (ProStrakan Ltd, Galashiels, UK) and Kalcipos-D 500 mg/800 IU (Meda Pharmaceuticals Ltd, Bishop's Stortford, UK), respectively.

Method: This phase IV, randomized, open-label, two-period, cross-over study was conducted at nine sites in the UK and Germany.

Exploratory Literature Meta-Analysis to Characterize the Relationship Between Early and Longer Term Body Weight Loss for Antiobesity Compounds.

The presented analysis was performed to characterize the relationship between treatment-related early (week 4) and longer term (3-6 months) weight loss to understand the potential utility of 4-week proof-of-mechanism studies in the early decision-making process during clinical development of new antiobesity compounds. A regression-based meta-analysis was performed leveraging publically available clinical outcomes data to (1) characterize the within-trial relationship between treatment-related early and longer term body weight loss and (2) identify and quantify key covariate effects on this relationship. Data from 89 randomized clinical trials with 209 treatment arms, representing observations from 54 461 patients and 9 treatments, were available for the meta-analysis.

An Overview of the Mechanism of Action of the Monoclonal Antibody Vedolizumab.

Vedolizumab is a novel therapeutic monoclonal antibody recently approved for the treatment of moderately to severely active ulcerative colitis and Crohn's disease in adults who have failed at least one conventional therapy. An integrin antagonist, vedolizumab binds to the αβ integrin which is expressed specifically by a subset of gastrointestinal-homing T lymphocytes. The binding of αβ integrin to mucosal addressin cell adhesion molecule-1 expressed on the surface of mucosal endothelial cells is a crucial component of the gut-selective homing mechanism for lymphocytes.

Epidemiology of lactic acidosis in type 2 diabetes patients with metformin in Japan.

Purpose: To estimate the incidence of lactic acidosis (LA) and role of metformin in Japanese patients with type 2 diabetes mellitus (T2DM) treated with anti-diabetes drugs.

Methods: This retrospective propensity score matched cohort study was conducted using the Japanese Medical Data Vision claims database. T2DM patients aged 18 or above who received diabetes drugs during January 2010 through August 2014 were identified.

True alignment of preclinical and clinical research to enhance success in CNS drug development: a review of the current evidence.

Central nervous system pharmacological research and development has reached a critical turning point. Patients suffering from disorders afflicting the central nervous system are numerous and command significant attention from the pharmaceutical industry. However, given the numerous failures of promising drugs, many companies are no longer investing in or, indeed, are divesting from this therapeutic area.

COPD exacerbations by disease severity in England.

Objectives: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013.

Methods: Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years.

A phase I randomized trial to assess the effect on skin infiltrate thickness and tolerability of topical phosphodiesterase inhibitors in the treatment of psoriasis vulgaris using a modified psoriasis plaque test.

Background: Oral phosphodiesterase (PDE)4 inhibitors have shown efficacy in chronic obstructive pulmonary disease and psoriasis.

Objectives: To assess the effectiveness, local safety and tolerability, and systemic pharmacokinetics of two topical PDE4 inhibitors, roflumilast and TAK-084, in plaque psoriasis.

Methods: An intraindividual comparison of six topical products was made in 15 patients aged 18-65 years with stable chronic plaque psoriasis in an investigator-blinded, within-subject randomized study.

Association between therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors and risk of ileus: a cohort study.

Background: Three cases of ileus have been published among dipeptidyl peptidase-4 (DPP-4) inhibitor users in Japan. The purpose of this study was to estimate and compare incidence rates of ileus among alogliptin users and users of other DPP-4 inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and voglibose.

Methods: We used the Medical Data Vision database in Japan to conduct a retrospective cohort study among type 2 diabetes mellitus (T2DM) patients who were new users of alogliptin, other DPP-4 inhibitors, GLP-1 receptor agonists, or voglibose between 1 April 2010 and 30 April 2014.

Fibrin Sealant Patch (TachoSil) vs Oxidized Regenerated Cellulose Patch (Surgicel Original) for the Secondary Treatment of Local Bleeding in Patients Undergoing Hepatic Resection: A Randomized Controlled Trial.

Background: Local hemostatic agents are important for the control of bleeding during liver resection when standard surgical techniques are insufficient.

Study Design: This was a multicenter, randomized, open-label study to compare fibrin sealant patch (FSP; TachoSil; Takeda Pharma A/S) with oxidized regenerated cellulose gauze (ORCG; Surgicel Original; Ethicon) for the secondary treatment of local bleeding after hepatic resection in adult and pediatric patients. Primary end point was the proportion of adult patients with intraoperative hemostasis at the target bleeding site within 3 minutes of application of treatment.

Single-dose pharmacokinetics and safety of azilsartan medoxomil in children and adolescents with hypertension as compared to healthy adults.

Purpose: This open-label, multicenter, single-dose study characterized the pharmacokinetics and short-term safety of azilsartan medoxomil (AZL-M) in hypertensive pediatric subjects (12-16 years [cohort 1a; n = 9]; 6-11 years [cohort 2; n = 8]; 4-5 years [cohort 3; n = 3]).

Methods: Model-based simulations were performed to guide dosing, especially in 1-5-year olds, who were difficult to enroll. AZL-M was dosed according to body weight (20-60-mg tablet, cohorts 1a and 2; 0.

Designing and incorporating a real world data approach to international drug development and use: what the UK offers.

Assessments of the safety, efficacy and appropriate use of new medicines lie at the heart of treatment development and subsequent adoption in clinical practice. Highly controlled randomised clinical trials routinely inform decisions on the approval, coverage and use of a medicine. Researchers and decision makers have become increasingly aware that these experimental data alone are insufficient to address those decisions fully.