SB16 versus reference denosumab in postmenopausal women with osteoporosis: 18-month outcomes of a phase III randomized clinical trial.

Purpose: This study evaluated the efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of SB16 versus reference denosumab (DEN) up to 18 months in postmenopausal osteoporosis (PMO) patients, and assessed outcomes after switching from DEN to SB16 compared to those who continued with DEN or SB16.

Methods: 457 PMO patients were initially randomized, with 407 re-randomized at Month 12 to either continue DEN (DEN+DEN), switch to SB16 (DEN+SB16), or continue SB16 (SB16 + SB16) through Month 18. Efficacy was assessed by the percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck.

Biosimilar SB17 versus reference ustekinumab in moderate to severe plaque psoriasis after switching: phase 3 study results up to week 52.

Introduction: SB17 is a biosimilar to reference ustekinumab (UST). We compared the efficacy, safety, and immunogenicity of SB17 to UST up to Week 52, including switching from UST to SB17.

Methods: Subjects were randomized to receive 45 mg of SB17 or UST subcutaneously up to Week 40.

A randomized, double-blind, phase III study assessing clinical similarity of SB17 (proposed ustekinumab biosimilar) to reference ustekinumab in subjects with moderate-to-severe plaque psoriasis.

Background: Ustekinumab (UST) is a safe and effective treatment for moderate-to-severe psoriasis.

Objectives: To compare efficacy, safety, pharmacokinetics (PK), and immunogenicity of the proposed UST biosimilar SB17 with reference UST in subjects with moderate-to-severe plaque psoriasis.

Methods: In this randomized double-blind study, subjects were randomized to receive 45 mg of SB17 or UST subcutaneously at week 0, 4, and every 12 weeks.

Usability of Prefilled Syringe and Autoinjector for SB4 (An Etanercept Biosimilar) in Patients with Rheumatoid Arthritis.

Introduction: This study aimed to compare the usability of subcutaneous administration of SB4 (an etanercept biosimilar) via prefilled syringe (PFS) and autoinjector (AI) based on injection site pain, patient preference, and safety in patients with rheumatoid arthritis (RA).

Methods: This was an open-label, single-arm, multicenter study to evaluate the usability and safety of the AI and PFS of SB4. Adult patients with RA received two injections of SB4 via the PFS, followed by six injections by the AI every week, up to 8 weeks.

Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study.

Objectives: Efficacy, safety and immunogenicity results from the phase III study of SB2, a biosimilar of reference infliximab (INF), were previously reported through 54 weeks. This transition period compared results in patients with rheumatoid arthritis (RA) who switched from INF to SB2 with those in patients who maintained treatment with INF or SB2.

Methods: Patients with moderate to severe RA despite methotrexate treatment were randomised (1:1) to receive SB2 or INF at weeks 0, 2 and 6 and every 8 weeks thereafter until week 46.

Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results.

Objectives: SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage.

A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy.

Objectives: To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy.

Methods: This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg.

Genetics of serum concentration of IL-6 and TNFα in systemic lupus erythematosus and rheumatoid arthritis: a candidate gene analysis.

Elevated concentrations of inflammatory mediators are characteristic of autoimmune disease accompanied by chronic or recurrent inflammation. We examined the hypothesis that mediators of inflammation known to be elevated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are associated with genetic polymorphism previously identified in studies of inflammatory disease. Serum interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) concentrations in patients with SLE (n = 117) or RA (n = 164) and in inflammatory disease-free control subjects (n = 172) were measured by multiplex ELISA.

Independent impact of gout on the risk of diabetes mellitus among women and men: a population-based, BMI-matched cohort study.

Objective: Evidence on the potential independent impact of gout on the risk of diabetes is limited to a single study of men with a high cardiovascular risk profile. Our objective was to examine this relation in the general population, particularly among women.

Methods: We conducted a sex-stratified matched cohort study using data from The Health Improvement Network (THIN), an electronic medical records database representative of the UK general population.

The comparative safety of tumor necrosis factor inhibitors in rheumatoid arthritis: a meta-analysis update of 44 trials.

Objective: The study objective was to evaluate and update the safety data from randomized controlled trials of tumor necrosis factor inhibitors in patients treated for rheumatoid arthritis.

Methods: A systematic literature search was conducted from 1990 to May 2013. All studies included were randomized, double-blind, controlled trials of patients with rheumatoid arthritis that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab treatment.

Allopurinol initiation and all-cause mortality in the general population.

Background: Allopurinol is the most commonly used urate-lowering therapy, with rare but potentially fatal adverse effects. However, its impact on overall mortality remains largely unknown. In this study, we evaluated the impact of allopurinol initiation on the risk of mortality among individuals with hyperuricaemia and among those with gout in the general population.

Associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis.

Objective: To investigate the associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis (RA).

Methods: We conducted a prospective study consisting of 662 patients with RA who were followed up to 7 years from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study. Smoking and alcohol consumption were assessed through yearly questionnaires.

Diabetes incidence in psoriatic arthritis, psoriasis and rheumatoid arthritis: a UK population-based cohort study.

Objective: The objective of this study was to evaluate the incidence of diabetes among patients with PsA and RA in the general population.

Methods: We conducted a cohort study using an electronic medical records database representative of the UK general population (1986-2010). We estimated hazard ratios (HRs) for incident diabetes in PsA, psoriasis and RA cohorts compared with age- and sex-matched comparison cohorts without the corresponding conditions, adjusting for BMI, smoking, alcohol use, co-morbidities and glucocorticoids at baseline.

Inflammation and hypertension in rheumatoid arthritis.

Objective: Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients with rheumatoid arthritis (RA), but the underlying mechanisms are unclear. We examined the hypothesis that mediators of inflammation and markers of cardiovascular risk are associated with HTN in RA.

Methods: We compared measures of inflammation [serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), homocysteine, and leptin concentrations] and insulin resistance [homeostasis model assessment index (HOMA)] in RA patients with (n = 90) and without HTN (n = 79).

The risk of pulmonary embolism and deep vein thrombosis in rheumatoid arthritis: a UK population-based outpatient cohort study.

Background: Recent hospital-based studies have suggested a sixfold increased risk of pulmonary embolism (PE) in rheumatoid arthritis (RA) in the year following admission. We evaluated the risk of PE and deep vein thrombosis (DVT) and associated time trend among RA patients (84.5% without a history of hospitalisation during the past year) derived from the general population.

The risk of cardiovascular disease in systemic sclerosis: a population-based cohort study.

Objectives: To evaluate the risk of incident myocardial infarction (MI), stroke and peripheral vascular disease (PVD) in individuals with systemic sclerosis (SSc) in a general population context.

Methods: We conducted a cohort study using a UK primary care database containing records from 1986 to 2011. SSc diagnoses, outcomes and cardiovascular risk factors were identified from electronic medical records.

Risk factors for pseudogout in the general population.

Objective. To evaluate the association between the purported risk factors for chondrocalcinosis and gout and the risk of pseudogout in the general population. Methods.

The epidemiology of uric acid and fructose.

During the past few decades, the mean serum uric acid levels and the prevalence of hyperuricemia in the general population appear to have increased. Correspondingly, the prevalence and incidence of gout have doubled. Potential reasons behind these trends include the increasing prevalence of obesity and metabolic syndrome, Western lifestyle factors, increased prevalence of medical conditions (eg, renal conditions, hypertension, and cardiovascular disorders), and use of medications that increase uric acid levels (eg, diuretics and low-dose aspirin).

Free fatty acids are associated with insulin resistance but not coronary artery atherosclerosis in rheumatoid arthritis.

Background: Free fatty acids (FFAs) affect insulin signaling and are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines such as interleukin-6 (IL-6) increase lipolysis and thus levels of FFAs. We hypothesized that increased IL-6 concentrations are associated with increased FFAs resulting in insulin resistance and atherosclerosis in rheumatoid arthritis (RA).

Cystatin C, renal function, and atherosclerosis in rheumatoid arthritis.

Objective: We examined the hypothesis that cystatin C, a novel marker of renal function, is elevated in rheumatoid arthritis (RA) and is associated with inflammation and coronary atherosclerosis.

Methods: We measured serum cystatin C, creatinine, tumor necrosis factor-α and interleukin 6 concentrations, coronary artery calcium score (CACS), and Modified Diet in Renal Disease estimated glomerular filtration rate in 167 patients with RA and 91 controls.

Results: Cystatin C was higher in RA patients [median (IQR) 1.

Macrophage activation and coronary atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis.

Objective: Activation of macrophages may contribute to increased atherosclerosis and coronary artery disease in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Neopterin, a pteridine derivative, is a novel marker of monocyte and macrophage activation that is associated with atherosclerosis and cardiovascular risk in the general population. We examined the hypothesis that macrophage activation is associated with accelerated atherosclerosis in SLE and RA.

Interaction between oxidative stress and high-density lipoprotein cholesterol is associated with severity of coronary artery calcification in rheumatoid arthritis.

Objective: To test the hypothesis that oxidative stress is increased in patients with rheumatoid arthritis (RA) due to increased inflammation and contributes to the pathogenesis of atherosclerosis.

Methods: The independent association between urinary F₂-isoprostane excretion, a measure of oxidative stress, and RA was tested using multiple linear regression models in 169 patients with RA and 92 control subjects, frequency matched for age, race, and sex. The relationship between F₂-isoprostane excretion and coronary calcium, a marker of atherosclerosis, was examined in multivariable proportional odds logistic regression models that also assessed the interactions between oxidative stress and low-density lipoprotein and high-density lipoprotein (HDL) cholesterol.

Adipocytokines, insulin resistance, and coronary atherosclerosis in rheumatoid arthritis.

Objective: The prevalence of subclinical coronary atherosclerosis is increased in patients with rheumatoid arthritis (RA), and the increased risk is associated with insulin resistance. Adipocytokines have been linked to obesity, insulin resistance, inflammation, and coronary heart disease in the general population. This study was undertaken to examine the hypothesis that adipocytokines affect insulin resistance and coronary atherosclerosis among patients with RA.