Two prospective, multicenter studies for the identification of biomarker signatures for early detection of pulmonary hypertension (PH): The CIPHER and CIPHER-MRI studies.

A blood test identifying patients at increased risk of pulmonary hypertension (PH) could streamline the investigative pathway. The prospective, multicenter CIPHER study aimed to develop a microRNA-based signature for detecting PH in breathless patients and enrolled adults with a high suspicion of PH who had undergone right heart catheterization (RHC). The CIPHER-MRI study was added to assess the performance of this CIPHER signature in a population with low probability of having PH who underwent cardiac magnetic resonance imaging (cMRI) instead of RHC.

Electrocardiogram Detection of Pulmonary Hypertension Using Deep Learning.

Background: Pulmonary hypertension (PH) is life-threatening, and often diagnosed late in its course. We aimed to evaluate if a deep learning approach using electrocardiogram (ECG) data alone can detect PH and clinically important subtypes. We asked: does an automated deep learning approach to ECG interpretation detect PH and its clinically important subtypes?

Methods And Results: Adults with right heart catheterization or an echocardiogram within 90 days of an ECG at the University of California, San Francisco (2012-2019) were retrospectively identified as PH or non-PH.

Efficacy and safety of the human anti-IL-1β monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study.

Background: Canakinumab is a fully human anti-interleukin IL-1beta monoclonal antibody, being investigated for the treatment of rheumatoid arthritis (RA). This multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study investigated the efficacy and safety of canakinumab in patients with active RA despite ongoing therapy at stable doses of methotrexate.

Methods: Patients were randomized to receive one of four regimens, in addition to methotrexate, for 12 weeks: canakinumab 150 mg subcutaneously (SC) every 4 weeks (q4wk), canakinumab 300 mg SC (2 injections of 150 mg SC) every 2 weeks, a 600 mg intravenous loading dose of canakinumab followed by 300 mg SC every 2 weeks', or placebo SC every 2 weeks.

Use of canakinumab in the cryopyrin-associated periodic syndrome.

Background: The cryopyrin-associated periodic syndrome (CAPS) is a rare inherited inflammatory disease associated with overproduction of interleukin-1. Canakinumab is a human anti-interleukin-1beta monoclonal antibody.

Methods: We performed a three-part, 48-week, double-blind, placebo-controlled, randomized withdrawal study of canakinumab in patients with CAPS.

A comparison of the blood pressure changes of lumiracoxib with those of ibuprofen and naproxen.

The 52-week Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) investigated the gastrointestinal and cardiovascular safety profile of lumiracoxib 400 mg once daily compared with 2 traditional nonsteroidal anti-inflammatory drugs (NSAIDs): ibuprofen 800 mg 3 times daily and naproxen 500 mg twice daily. Data from TARGET were analyzed to examine the effect of lumiracoxib compared with ibuprofen and naproxen on blood pressure (BP), incidence of de novo and aggravated hypertension, prespecified edema events, and congestive heart failure. Lumiracoxib resulted in smaller changes in BP as early as week 4.

Efficacy and tolerability of lumiracoxib 200 mg once daily for treatment of primary dysmenorrhea: results from two randomized controlled trials.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are established as treatment for managing pain associated with primary dysmenorrhea. However, the efficacy and tolerability of lumiracoxib 200 mg once daily (q.d.

Effect of risk factors on complicated and uncomplicated ulcers in the TARGET lumiracoxib outcomes study.

Background & Aims: Selective cyclooxygenase-2 inhibitors were developed to reduce the gastrointestinal risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs). The Therapeutic Arthritis Research and Gastrointestinal Event Trial was the largest study to evaluate primarily the gastrointestinal safety outcomes of selective cyclooxygenase-2 inhibitors. Data from the Therapeutic Arthritis Research and Gastrointestinal Event Trial were used to identify risk factors and investigate the safety of lumiracoxib in subgroups.

Evaluation of the patient acceptable symptom state in a pooled analysis of two multicentre, randomised, double-blind, placebo-controlled studies evaluating lumiracoxib and celecoxib in patients with osteoarthritis.

Unlabelled: Patient Acceptable Symptom State (PASS) is an absolute threshold proposed for symptomatic variables in osteoarthritis (OA) to determine the point beyond which patients consider themselves well and, as such, are satisfied with treatment. Two large previously reported studies of knee OA have shown that both lumiracoxib and celecoxib were superior to placebo in terms of conventional outcome measures. To assess the clinical relevance of these results from the patient's perspective, the same data pooled from these two studies were analysed with respect to the PASS.

Gastrointestinal tolerability of lumiracoxib in patients with osteoarthritis and rheumatoid arthritis.

Background & Aims: The aim of this study was to evaluate the gastrointestinal safety of lumiracoxib, a novel selective cyclooxygenase-2 inhibitor.

Methods: Results from 15 Phase II and III randomized studies of lumiracoxib in osteoarthritis and rheumatoid arthritis were pooled. Patients received lumiracoxib (200/400 mg/day), celecoxib (200/400 mg/day), rofecoxib (25 mg once daily), diclofenac (75 mg twice daily), ibuprofen (800 mg 3 times daily), naproxen (500 mg twice daily), or placebo.

Cardiovascular safety of lumiracoxib: a meta-analysis of all randomized controlled trials > or =1 week and up to 1 year in duration of patients with osteoarthritis and rheumatoid arthritis.

Background: The cardiovascular (CV) safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors has been the subject of considerable debate.

Objective: The objective of this study was to determine the risk of CV events with lumiracoxib by meta-analysis of all completed, randomized controlled trials (RCTs) of > or =1 week and up to 1 year in duration of patients with osteoarthritis and rheumatoid arthritis.

Methods: The Novartis Lumiracoxib Clinical Trial Database, which includes all clinical studies conducted to date with lumiracoxib, was reviewed.

Lumiracoxib in the treatment of osteoarthritis, rheumatoid arthritis and acute postoperative dental pain: results of three dose-response studies.

Objectives: Overview of three dose-response studies demonstrating the efficacy of lumiracoxib, a novel COX-2 selective inhibitor, for chronic pain associated with osteoarthritis (0A), or rheumatoid arthritis (RA) and acute pain following dental extraction.

Methods: OA and RA: 4-week, randomized, placebo- and active-controlled studies of similar design. Patients (OA, n = 583; RA, n = 571) received lumiracoxib 50 mg, 100 mg or 200 mg twice daily (bid), lumiracoxib 400 mg once daily (od), diclofenac 75 mg bid or placebo.

Gastroduodenal safety and tolerability of lumiracoxib compared with Ibuprofen and celecoxib in patients with osteoarthritis.

Objective: To compare the incidence of gastroduodenal ulcers in patients with osteoarthritis (OA) treated with therapeutic doses of the novel COX-2 selective inhibitor, lumiracoxib (COX189, Prexige), and the standard nonsteroidal antiinflammatory drug (NSAID) ibuprofen. The COX-2 selective inhibitor celecoxib was included as an active control.

Methods: In this randomized, multicenter, double-blind, parallel-group study, eligible patients were randomized to receive lumiracoxib 200 mg (n = 264) or 400 mg (n = 260) once daily (qd), ibuprofen 800 mg (n = 260) 3 times daily (tid), or celecoxib 200 mg qd (n = 258) for 13 weeks.

Efficacy and safety of four doses of lumiracoxib versus diclofenac in patients with knee or hip primary osteoarthritis: a phase II, four-week, multicenter, randomized, double-blind, placebo-controlled trial.

Objective: To compare the efficacy and tolerability of the novel cyclooxygenase 2-selective inhibitor lumiracoxib with placebo and diclofenac in osteoarthritis (OA).

Methods: Adults (n=583) with knee or hip OA were randomized to receive for 4 weeks lumiracoxib 50, 100, or 200 mg twice daily or 400 mg once daily; placebo; or diclofenac 75 mg twice daily. Efficacy assessments included overall joint pain intensity and Western Ontario and McMaster Universities Osteoarthritis Index subscales; tolerability was evaluated by adverse event and physician reporting.

Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial.

Background: The potential for cyclo-oxygenase 2 (COX2)-selective inhibitors to increase the risk for myocardial infarction is controversial. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs, naproxen and ibuprofen.

Methods: 18325 patients age 50 years or older with osteoarthritis were randomised to lumiracoxib 400 mg once daily (n=9156), naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) in two substudies of identical design.

Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial.

Background: Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with non-selective non-steroidal anti-inflammatory drugs, but evidence is limited, and the possibility that these inhibitors increase cardiovascular events has been raised. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs, naproxen and ibuprofen.

Methods: 18325 patients age 50 years or older with osteoarthritis were randomised to lumiracoxib 400 mg once daily (n=9156), naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) for 52 weeks, in two substudies of identical design (lumiracoxib vs ibuprofen or naproxen).