Maintenance of remission with combination etanercept-DMARD therapy versus DMARDs alone in active rheumatoid arthritis: results of an international treat-to-target study conducted in regions with limited biologic access.

In this transglobal, randomized, double-blind, placebo-controlled, treat-to-target study, the maintenance of efficacy was compared between biologic-and biologic-free-disease-modifying antirheumatic drug (DMARD) combination regimens after low disease activity (LDA) was achieved with biologic DMARD induction therapy. Patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy received open-label etanercept 50 mg subcutaneously once weekly plus methotrexate with or without other conventional synthetic (cs) DMARDs for 24 weeks. Patients achieving LDA [disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) <3.

Correction: The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.

[This corrects the article DOI: 10.1371/journal.pone.

The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.

Objective: To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes.

Methods: This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6-24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose.

The prevalence and clinical characteristics of nonradiographic axial spondyloarthritis among patients with inflammatory back pain in rheumatology practices: a multinational, multicenter study.

Background: Patients with ankylosing spondylitis (AS), who by definition have radiographic sacroiliitis, typically experience symptoms for a decade or more before being diagnosed. Yet, even patients without radiographic sacroiliitis (i.e.

Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double-blind, placebo-controlled trial.

Objective: To assess the efficacy of etanercept in the treatment of early active nonsteroidal antiinflammatory drug (NSAID)-refractory nonradiographic axial spondyloarthritis (SpA).

Methods: The study population consisted of patients who met the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA but not the modified New York radiographic criteria for ankylosing spondylitis (as assessed by a radiologist at the central trial site), had a symptom duration of >3 months but <5 years, had a score of ≥4 on the Bath Ankylosing Spondylitis Disease Activity Index, and had been treated unsuccessfully with ≥2 NSAIDs. Patients were randomized to receive etanercept 50 mg/week or placebo and continued background NSAID treatment for 12 weeks (double-blind study); during the subsequent open-label period, all patients received etanercept 50 mg/week.

Effect of golimumab on carotid atherosclerotic disease measures and cardiovascular events in inflammatory arthritides.

Objective: The objective of this study was to assess the effect of golimumab on carotid ultrasound measures and cardiovascular serious adverse events (SAEs) in patients with inflammatory arthritides.

Methods: An exploratory carotid artery ultrasound substudy was performed in the GO-BEFORE study of methotrexate (MTX)-naive rheumatoid arthritis patients, with ultrasounds performed at weeks 0, 24, and 52 to measure common carotid artery intima-media thickness, distensibility coefficient, interadventitial diameter, and plaque count. Cardiovascular SAEs reported over 2 years of follow-up were assessed in 5 golimumab phase 3 clinical trials of patients with rheumatoid arthritis (GO-BEFORE, GO-FORWARD, and GO-AFTER), psoriatic arthritis (GO-REVEAL), and ankylosing spondylitis (GO-RAISE).

Risk of tuberculosis with anti-tumor necrosis factor-α therapy: substantially higher number of patients at risk in Asia.

Aim: To assess the potential risk of tuberculosis (TB) in patients treated with anti-tumor necrosis factor-alpha (TNF-α) agents in Asia.

Methods: Absolute risk increase (ARI) of TB was estimated for three widely used anti-TNF-α therapies using published standardized incidence ratios (SIR) from the French Research Axed on Tolerance of bIOtherapies registry and incidence (absolute risk [AR]) of TB in Asia. Assuming an association of increased TB risk with anti-TNF-α therapy and country TB AR (incidence), the ARI of TB by country was calculated by multiplying the SIR of the anti-TNF-α therapy by the country's TB AR.

The effect of golimumab on haemoglobin levels in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.

Objective: To evaluate the effect of golimumab on haemoglobin levels in patients with RA, PsA or AS.

Methods: Secondary analysis was performed on integrated data from five randomized controlled studies: three RA, one PsA and one AS (2303 patients total). Golimumab 50 or 100 mg was injected s.

Changes in biomarkers after therapeutic intervention in temporal arteries cultured in Matrigel: a new model for preclinical studies in giant-cell arteritis.

Background: Search for therapeutic targets in giant-cell arteritis (GCA) is hampered by the scarcity of functional systems. We developed a new model consisting of temporal artery culture in tri-dimensional matrix and assessed changes in biomarkers induced by glucocorticoid treatment.

Methods: Temporal artery sections from 28 patients with GCA and 22 controls were cultured in Matrigel for 5 days in the presence or the absence of dexamethasone.

Effects of subcutaneous and intravenous golimumab on inflammatory biomarkers in patients with rheumatoid arthritis: results of a phase 1, randomized, open-label trial.

Objective: To evaluate the effects of the anti-TNF-α monoclonal antibody golimumab, administered by s.c. injection or i.

Effects of golimumab, an anti-tumour necrosis factor-α human monoclonal antibody, on lipids and markers of inflammation.

Objectives: To assess the effect of golimumab, with or without methotrexate (MTX), on serum lipids and inflammatory markers of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) in two phase 3, randomised, placebo-controlled trials (GO-BEFORE and GO-FORWARD).

Methods: Patients in GO-BEFORE (n=637, MTX-naïve) and GO-FORWARD (n=444, MTX-inadequate response) were randomised to placebo+MTX, golimumab 100 mg+placebo, golimumab 50 mg+MTX, or golimumab 100 mg+MTX. Subcutaneous injections (placebo and golimumab) were given every 4 weeks.

Increased IL-17A expression in temporal artery lesions is a predictor of sustained response to glucocorticoid treatment in patients with giant-cell arteritis.

Background: Interleukin 17A (IL-17A) exerts pivotal proinflammatory functions in chronic inflammatory and autoimmune diseases.

Objective: To investigate IL-17A expression in temporal artery lesions from patients with giant-cell arteritis (GCA), and its relationship with disease outcome.

Methods: Fifty-seven patients with biopsy-proven GCA were prospectively evaluated, treated and followed for 4.

Comprehensive tuberculosis screening program in patients with inflammatory arthritides treated with golimumab, a human anti-tumor necrosis factor antibody, in Phase III clinical trials.

Objective: Reactivation of Mycobacterium tuberculosis infection is a major complication in patients treated with anti-tumor necrosis factor (anti-TNF) agents. We report on the 5 cases of active tuberculosis (TB) that developed in the Golimumab Phase III Program (3 with rheumatoid arthritis, 1 with psoriatic arthritis, and 1 with ankylosing spondylitis) through 1 year among 2,210 patients receiving golimumab.

Methods: Data from global studies were used for an in-depth evaluation of the 5 cases of TB through week 52.

Effect of golimumab on patient-reported outcomes in rheumatoid arthritis: results from the GO-FORWARD study.

Objective: To evaluate the effect of golimumab on physical function, general health, and fatigue in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.

Methods: In the multicenter, randomized, placebo-controlled GO-FORWARD study, 444 adults with active RA despite MTX received subcutaneous placebo + MTX (crossover to golimumab 50 mg at Week 24), golimumab 100 mg + placebo, golimumab 50 mg + MTX, or golimumab 100 mg + MTX every 4 weeks. Physical function and general health were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and Physical and Mental Component Summary (PCS, MCS) scores of the Medical Outcomes Study Short Form-36 questionnaire (SF-36), respectively, through Week 52.

Golimumab in psoriatic arthritis: one-year clinical efficacy, radiographic, and safety results from a phase III, randomized, placebo-controlled trial.

Objective: Golimumab, administered subcutaneously every 4 weeks, has been shown to be effective in reducing the signs and symptoms of active psoriatic arthritis (PsA) through week 24 of the GO-REVEAL study. Herein we report 1-year clinical, radiographic, and safety findings.

Methods: Adult patients with active PsA (≥3 swollen and ≥3 tender joints) were randomly assigned to receive subcutaneous placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks through week 20.

Interferon-γ release assay versus tuberculin skin test prior to treatment with golimumab, a human anti-tumor necrosis factor antibody, in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.

Objective: To evaluate the performance of an interferon-γ release assay (IGRA) versus the standard tuberculin skin test (TST) as a screening tool for latent tuberculosis (TB) infection prior to the initiation of anti-tumor necrosis factor therapy in patients with autoimmune inflammatory diseases.

Methods: This integrated analysis involved screening of patients with rheumatoid arthritis, those with psoriatic arthritis, and those with ankylosing spondylitis from phase III trials of golimumab. The IGRA used to screen for latent TB was the QuantiFERON-TB Gold In-Tube test.

Significant improvement in synovitis, osteitis, and bone erosion following golimumab and methotrexate combination therapy as compared with methotrexate alone: a magnetic resonance imaging study of 318 methotrexate-naive rheumatoid arthritis patients.

Objective: To evaluate the effects of golimumab on inflammation/structural damage detected by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA).

Methods: Methotrexate (MTX)-naive RA patients (n = 637) were randomized to placebo plus MTX, golimumab 100 mg plus placebo, golimumab 50 mg plus MTX, or golimumab 100 mg plus MTX (subcutaneous golimumab every 4 weeks). Of these, 318 patients participated in an MRI substudy.

Exploratory analyses of the association of MRI with clinical, laboratory and radiographic findings in patients with rheumatoid arthritis.

Objectives: Evaluate relationships between MRI and clinical/laboratory/radiographic findings in rheumatoid arthritis (RA).

Methods: 637 methotrexate-naive patients (GO-BEFORE) and 444 patients with active RA despite methotrexate (GO-FORWARD) were randomly assigned to subcutaneous placebo + methotrexate, golimumab 100mg + placebo, golimumab 50mg + methotrexate, or golimumab 100mg + methotrexate every-4-weeks. In GO-BEFORE(n=318) and GO-FORWARD(n=240) substudies, MRI of dominant wrist/metacarpophalangeal joints were scored for synovitis, bone oedema and bone erosion (RA MRI scoring (RAMRIS) system).

Tissue and serum markers of inflammation during the follow-up of patients with giant-cell arteritis--a prospective longitudinal study.

Objective: To evaluate the association between inflammatory markers and relapse in GCA patients longitudinally assessed in a clinical trial of infliximab and glucocorticosteroids.

Methods: Forty-four newly diagnosed GCA patients in glucocorticosteroid-induced remission were randomized to receive infliximab 5 mg/kg or placebo plus daily glucocorticosteroids, tapered using a standardized schedule. Sera were analysed for inflammatory markers at multiple, pre-defined time points.

Assessment by MRI of inflammation and damage in rheumatoid arthritis patients with methotrexate inadequate response receiving golimumab: results of the GO-FORWARD trial.

Objective: To evaluate golimumab's effect on MRI-detected inflammation and structural damage in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX).

Methods: Patients (n=444) were randomly assigned to placebo plus MTX, golimumab 100 mg plus placebo, golimumab 50 mg plus MTX, or golimumab 100 mg plus MTX (subcutaneous injections every 4 weeks). A subset of 240 patients participated in an MRI substudy.

Changes in patient characteristics in anti-tumour necrosis factor clinical trials for rheumatoid arthritis: results of an analysis of the literature over the past 16 years.

Objective: To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNFα) inhibitors in rheumatoid arthritis (RA) patients.

Methods: A systematic literature review was performed using predefined inclusion criteria to identify randomised, double-blind, controlled trials that evaluated TNFα inhibitors in adult RA patients. Entry criteria and baseline clinical characteristics were evaluated over time for methotrexate-experienced and methotrexate-naive study populations.

Diabetes mellitus and insulin resistance in patients with rheumatoid arthritis: risk reduction in a chronic inflammatory disease.

Objective: To perform a systematic literature review of the potential association among molecular markers of inflammation, alterations in body composition, and insulin resistance (IR), a precursor to type 2 diabetes mellitus (DM), in rheumatoid arthritis (RA) patients. To determine the impact of tumor necrosis factor α (TNFα) as a pivotal proinflammatory cytokine in the pathophysiology of type 2 DM and RA, and the effect of antirheumatic drugs on glycemic control.

Methods: We performed a search of PubMed to identify articles on IR and body habitus in patients with RA.

Predicting the outcome of ankylosing spondylitis therapy.

Objectives: To create a model that provides a potential basis for candidate selection for anti-tumour necrosis factor (TNF) treatment by predicting future outcomes relative to the current disease profile of individual patients with ankylosing spondylitis (AS).

Methods: ASSERT and GO-RAISE trial data (n=635) were analysed to identify baseline predictors for various disease-state and disease-activity outcome instruments in AS. Univariate, multivariate, receiver operator characteristic and correlation analyses were performed to select final predictors.