A framework for longitudinal latent factor modelling of treatment response in clinical trials with applications to Psoriatic Arthritis and Rheumatoid Arthritis.

Objective: Clinical trials involve the collection of a wealth of data, comprising multiple diverse measurements performed at baseline and follow-up visits over the course of a trial. The most common primary analysis is restricted to a single, potentially composite endpoint at one time point. While such an analytical focus promotes simple and replicable conclusions, it does not necessarily fully capture the multi-faceted effects of a drug in a complex disease setting.

VertXNet: an ensemble method for vertebral body segmentation and identification from cervical and lumbar spinal X-rays.

Accurate annotation of vertebral bodies is crucial for automating the analysis of spinal X-ray images. However, manual annotation of these structures is a laborious and costly process due to their complex nature, including small sizes and varying shapes. To address this challenge and expedite the annotation process, we propose an ensemble pipeline called VertXNet.

A deep learning approach to private data sharing of medical images using conditional generative adversarial networks (GANs).

Clinical data sharing can facilitate data-driven scientific research, allowing a broader range of questions to be addressed and thereby leading to greater understanding and innovation. However, sharing biomedical data can put sensitive personal information at risk. This is usually addressed by data anonymization, which is a slow and expensive process.

Quantification of pre-existing radiographic damage and its relationship with joint activity and long-term clinical outcomes with secukinumab therapy in patients with psoriatic arthritis.

Background: Psoriatic arthritis (PsA) patient data from two phase 3 secukinumab trials (FUTURE 1, 5) were analysed to quantify the prevalence and extent of pre-existing radiographic damage (RD) at baseline; investigate the association of RD with swollen/tender joint counts (SJC/TJC) at baseline; and investigate the extent to which RD at baseline correlated with response to secukinumab.

Methods: Pooled data (N = 1554) provided baseline radiographic bone erosion and joint space narrowing (JSN) scores at pre-specified locations per the van der Heijde-modified total Sharp score (vdH-mTSS) for PsA and swollen and tender joint scores in the same joints at multiple visits. Overall patient RD and individual joints RD bone erosion and JSN scores were assessed.

Clinically relevant patient clusters identified by machine learning from the clinical development programme of secukinumab in psoriatic arthritis.

Objectives: Identify distinct clusters of psoriatic arthritis (PsA) patients based on their baseline articular, entheseal and cutaneous disease manifestations and explore their clinical and therapeutic value.

Methods: Pooled baseline data in PsA patients (n=1894) treated with secukinumab across four phase 3 studies (FUTURE 2-5) were analysed to determine phenotypes based on clusters of clinical indicators. Finite mixture models methodology was applied to generate clinical clusters and mean longitudinal responses were compared between secukinumab doses (300 vs 150 mg) across identified clusters and clinical indicators through week 52 using machine learning (ML) techniques.

Secukinumab Efficacy in Psoriatic Arthritis: Machine Learning and Meta-analysis of Four Phase 3 Trials.

Background: Using a machine learning approach, the study investigated if specific baseline characteristics could predict which psoriatic arthritis (PsA) patients may gain additional benefit from a starting dose of secukinumab 300 mg over 150 mg. We also report results from individual patient efficacy meta-analysis (IPEM) in 2049 PsA patients from the FUTURE 2 to 5 studies to evaluate the efficacy of secukinumab 300 mg, 150 mg with and without loading regimen versus placebo at week 16 on achievement of several clinically relevant difficult-to-achieve (higher hurdle) endpoints.

Methods: Machine learning employed Bayesian elastic net to analyze baseline data of 2148 PsA patients investigating 275 predictors.

Secukinumab provides sustained low rates of radiographic progression in psoriatic arthritis: 52-week results from a phase 3 study, FUTURE 5.

Objective: To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study.

Methods: Patients with active PsA, stratified by prior anti-TNF use (naïve or inadequate response), were randomized to s.c.

Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis.

Methods: In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4.

One-year efficacy and safety results of secukinumab in patients with rheumatoid arthritis: phase II, dose-finding, double-blind, randomized, placebo-controlled study.

Objective: To evaluate the longer-term safety and efficacy of secukinumab, a fully human monoclonal antiinterleukin-17A antibody, in patients with rheumatoid arthritis.

Methods: In this 52-week, double-blind, placebo-controlled (up to Week 20) study (NCT00928512), patients responding inadequately to disease-modifying antirheumatic drugs (DMARD) or biologics were randomized to receive monthly subcutaneous injections of secukinumab (25, 75, 150, or 300 mg), or placebo. The efficacy and safety results up to Week 20 have been reported previously.

Long-term tegaserod treatment for dysmotility-like functional dyspepsia: results of two identical 1-year cohort studies.

Background: Functional dyspepsia (FD) is a chronic disorder that adversely affects health-related quality of life (HRQoL). Published information on its long-term management is minimal and treatment options are limited.

Aim: The aim of this study was to evaluate safety, efficacy and HRQoL with tegaserod 6 mg twice daily over 1 year in women with FD who completed one of two 6-week, randomized, placebo-controlled, double-blind studies.

Tegaserod treatment for dysmotility-like functional dyspepsia: results of two randomized, controlled trials.

Objectives: Therapies for dysmotility-like functional dyspepsia (FD) are limited. We studied tegaserod, a selective serotonin type 4 receptor agonist, in patients with FD.

Methods: Two identical multicenter, double-blind, randomized, placebo-controlled trials enrolled women >/=18 yr with recurring mid-upper abdominal discomfort characterized by postprandial fullness, early satiety, and/or bloating.

Tegaserod for female patients suffering from IBS with mixed bowel habits or constipation: a randomized controlled trial.

Objectives: Though the greatest proportion of irritable bowel syndrome (IBS) patients report a mixed bowel pattern (IBS-Mixed), no available therapies have been rigorously evaluated in this subgroup. This study aimed to evaluate the efficacy and safety of the 5-HT(4) agonist tegaserod in women with IBS-Mixed and IBS with constipation (IBS-C).

Methods: This prospective, double-blind, randomized, placebo-controlled, multicenter study was conducted in 100 centers in North America, South America, and Europe.

Omeprazole-induced slowing of gastrointestinal transit in mice can be countered with tegaserod.

Omeprazole, besides suppressing gastric acid, causes delayed gastric emptying, which may be associated with aggravated dyspeptic symptoms. Effects of omeprazole on small intestinal transit are unknown. In this study, we evaluated in mice if (a) omeprazole affects transit of a meal through the stomach and small intestine and (b) co-treatment with the promotility agent, tegaserod, can prevent the slowing effect of omeprazole.