Cardiovascular Safety of Tocilizumab Versus Etanercept in Rheumatoid Arthritis: A Randomized Controlled Trial.

Objective: To assess the risk of major adverse cardiovascular events (MACE) in patients with rheumatoid arthritis (RA) treated with tocilizumab compared to those treated with the tumor necrosis factor inhibitor etanercept.

Methods: This randomized, open-label, parallel-group trial enrolled patients with active seropositive RA (n = 3,080) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs and who had at least 1 cardiovascular (CV) risk factor. Patients were randomly assigned 1:1 to receive open-label tocilizumab at 8 mg/kg/month or etanercept at 50 mg/week.

Glucocorticoid Dosages and Acute-Phase Reactant Levels at Giant Cell Arteritis Flare in a Randomized Trial of Tocilizumab.

Objective: This study was undertaken to evaluate glucocorticoid dosages and serologic findings in patients with giant cell arteritis (GCA) flares.

Methods: Patients with GCA were randomly assigned to receive double-blind dosing with either subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week prednisone taper (TCZ-QW + Pred-26), every-other-week TCZ plus 26-week prednisone taper (TCZ-Q2W + Pred-26), placebo plus 26-week prednisone taper (PBO + Pred-26), or placebo plus 52-week prednisone taper (PBO + Pred-52). Outcome measures were prednisone dosage, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare.

Health-related quality of life in patients with giant cell arteritis treated with tocilizumab in a phase 3 randomised controlled trial.

Background: Patients with giant cell arteritis (GCA) treated with tocilizumab (TCZ) every week or every other week and prednisone tapering achieved superior rates of sustained remission to patients treated with placebo and prednisone tapering in a randomised controlled trial. Health-related quality of life (HRQOL) in patients from this trial is now reported.

Methods: Exploratory analyses of SF-36 PCS and MCS and domain scores, PtGA and FACIT-Fatigue were performed in patients treated with weekly subcutaneous TCZ 162 mg plus 26-week prednisone taper (TCZ-QW + Pred-26) or placebo plus 26-week or 52-week prednisone tapers (PBO + Pred-26 or PBO + Pred-52).

No difference in cardiovascular risk of tocilizumab versus abatacept for rheumatoid arthritis: A multi-database cohort study.

Objectives: While tocilizumab may increase serum lipid levels, recent studies do not suggest a link between tocilizumab use and clinical cardiovascular risk in patients with rheumatoid arthritis (RA).

Methods: To compare cardiovascular safety of tocilizumab with abatacept, we conducted a cohort study using data from Medicare (2010-2013), IMS PharMetrics (2011-2014) and MarketScan (2011-6/2015). RA patients aged ≥18 years who newly started tocilizumab or abatacept entered the cohort on the day of their first use of tocilizumab or abatacept after a continuous enrollment period for ≥365 days.

Trial of Tocilizumab in Giant-Cell Arteritis.

Background: Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis.

Methods: In this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks.

Cardiovascular Safety of Tocilizumab Versus Tumor Necrosis Factor Inhibitors in Patients With Rheumatoid Arthritis: A Multi-Database Cohort Study.

Objective: While tocilizumab (TCZ) is known to increase low-density lipoprotein (LDL) cholesterol levels, it is unclear whether TCZ increases cardiovascular risk in patients with rheumatoid arthritis (RA). This study was undertaken to compare the cardiovascular risk associated with receiving TCZ versus tumor necrosis factor inhibitors (TNFi).

Methods: To examine comparative cardiovascular safety, we conducted a cohort study of RA patients who newly started TCZ or TNFi using claims data from Medicare, IMS PharMetrics, and MarketScan.

Serious adverse effects associated with glucocorticoid therapy in patients with giant cell arteritis (GCA): A nested case-control analysis.

Objective: Giant cell arteritis (GCA) is an inflammatory vasculitis preferentially affecting large and medium-sized arteries. High-dose oral glucocorticoids (GCs) are the mainstay of GCA therapy. Using data from the UK Clinical Practice Research Datalink (CPRD), we examined the risk of oral GC-related serious adverse events (SAEs) in a UK population of patients with giant cell arteritis (GCA).

Newly diagnosed vs. relapsing giant cell arteritis: Baseline data from the GiACTA trial.

Objective: To report entry criteria and clinical features of patients with newly diagnosed and relapsing giant cell arteritis (GCA) enrolled in a randomized trial of tocilizumab, an interleukin-6 receptor-alpha inhibitor.

Methods: Newly diagnosed GCA was defined as diagnosis ≤6 weeks before baseline. Relapsing GCA was defined as diagnosis >6 weeks before baseline with ≥2 consecutive weeks of prednisone ≥40mg/day.

Incidence of outcomes potentially associated with corticosteroid therapy in patients with giant cell arteritis.

Objective: Giant cell arteritis (GCA) is an inflammatory disorder of blood vessels that preferentially affects large- and medium-sized arteries. High-dose oral corticosteroids (CS) are the mainstay of GCA therapy. Using data from the UK Clinical Practice Research Datalink, we quantified and compared the incidence of selected potentially CS-associated adverse outcomes in patients with and without GCA.

Corticosteroid-related adverse events in patients with giant cell arteritis: A claims-based analysis.

Objective: Corticosteroids (CS) are standard treatment for giant cell arteritis (GCA), but concerns persist over toxicities associated with long-term use. In this retrospective study of medical claims data, we estimated risks for adverse events (AEs) in CS-treated GCA patients.

Methods: Cox regression analyses with CS use as a time-dependent variable were conducted on data from the 2003 to 2012 Truven Health Analytics MarketScan Database.

Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis.

Objective: Compare changes in lipids and lipid-associated cardiovascular (CV) risk markers in patients with rheumatoid arthritis (RA) treated with tocilizumab or adalimumab.

Methods: Post-hoc analysis was performed in patients with RA who received tocilizumab intravenously every 4 weeks or adalimumab subcutaneously every 2 weeks for 24 weeks in the ADACTA trial. Lipid and lipid-associated CV risk biomarkers, including high-density lipoprotein-associated serum amyloid-A (HDL-SAA), secretory phospholipase A2 IIA (sPLA2 IIA) and lipoprotein(a) (Lp(a)), were measured at baseline and at week 8.

Development and implementation of a double-blind corticosteroid-tapering regimen for a clinical trial.

We describe the design and operationalization of a blinded corticosteroid-tapering regimen for a randomized trial of tocilizumab in giant cell arteritis (GCA). To our knowledge, no clinical trial in any disease has ever employed a blinded corticosteroid-tapering regimen, but this was necessary to the design of our trial which is likely to be relevant to other investigations of steroid-sparing regimens. Two standardized corticosteroid-tapering regimens are required for this GCA trial: a 6-month regimen in 3 arms (taken with tocilizumab 162 mg subcutaneously weekly or every other week or with placebo) and a 12-month regimen with placebo (fourth arm).

An evaluation of risk factors for major adverse cardiovascular events during tocilizumab therapy.

Objective: To evaluate associations between lipid levels, inflammation, and rheumatoid arthritis (RA) disease activity, at baseline and during treatment, with the risk of major adverse cardiovascular events (MACE) in tocilizumab-treated patients with RA.

Methods: In retrospective post hoc analyses, data were pooled for 3,986 adult patients with moderate to severe RA who received ≥1 dose of tocilizumab (4 mg/kg or 8 mg/kg) intravenously every 4 weeks in randomized controlled trials and extension studies. Cox proportional hazards modeling was used to evaluate associations between baseline characteristics and posttreatment changes in laboratory and disease characteristics (week 24) and change in disease activity and laboratory values from baseline to week 24 with the risk of future MACE during extended followup.

Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics.

Introduction: Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Currently, the relationship between pathogenic molecular drivers of disease in RA and therapeutic response is poorly understood.

Methods: We analyzed synovial tissue samples from two RA cohorts of 49 and 20 patients using a combination of global gene expression, histologic and cellular analyses, and analysis of gene expression data from two further publicly available RA cohorts.

Humoral immune response to vaccines in patients with rheumatoid arthritis treated with tocilizumab: results of a randomised controlled trial (VISARA).

Objective: To evaluate the effect of tocilizumab (TCZ), an interleukin 6 receptor inhibitor, on humoral immune responses to immunisations in patients with rheumatoid arthritis (RA).

Methods: Patients with RA with inadequate response/intolerance to one or more anti-tumour necrosis factor-α agents were randomly assigned (2:1) to TCZ 8 mg/kg intravenously every 4 weeks plus methotrexate (MTX) or MTX alone up until week 8. Serum was collected before vaccination at week 3, antibody titres were evaluated at week 8, and then all patients received TCZ+MTX through week 20.

Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial.

Background: Roughly a third of patients with rheumatoid arthritis treated with biological treatments receive them as monotherapy. Tocilizumab--an inhibitor of interleukin 6 receptor signalling--has been studied as monotherapy in several clinical trials. We assessed the efficacy and safety of tocilizumab monotherapy compared with adalimumab monotherapy for patients with rheumatoid arthritis.