Clinical outcomes of patients with giant cell arteritis treated with tocilizumab in real-world clinical practice: decreased incidence of new visual manifestations.

Background: Placebo-controlled clinical trials have demonstrated the efficacy of tocilizumab (TCZ) for remission maintenance and glucocorticoid sparing in patients with giant cell arteritis (GCA). However, limited data exist on the effectiveness and safety of TCZ for GCA in real-world clinical practice.

Methods: This was a retrospective, single-center analysis of patients with GCA treated with intravenous or subcutaneous TCZ (2010-2018).

Magnetic Resonance Imaging (MRI) Results Following Discontinuation of Methotrexate in Rheumatoid Arthritis Treated with Subcutaneous Tocilizumab: The COMP-ACT MRI Substudy.

Objective: To assess differences in joint damage and inflammation using magnetic resonance imaging (MRI) between patients with rheumatoid arthritis (RA) who achieved low disease activity with tocilizumab (TCZ) + methotrexate (MTX) and subsequently continued or discontinued MTX.

Methods: In the COMP-ACT trial, US patients with RA received subcutaneous TCZ 162 mg + MTX. Those who achieved 28-joint count Disease Activity Score calculated with erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.

Adverse Events in Giant Cell Arteritis and Rheumatoid Arthritis Patient Populations: Analyses of Tocilizumab Clinical Trials and Claims Data.

Introduction: The safety profile of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) is well established. TCZ was approved to treat giant cell arteritis (GCA) in 2017 in the USA and Europe, and its safety profile in patients with GCA continues to be defined. The objective of this analysis was to examine incidence rates (IRs) of adverse events of special interest (AESI) occurring during the TCZ clinical development program and in healthcare claims data in patients with GCA or RA.

Impact of tocilizumab administered intravenously or subcutaneously on patient-reported quality-of-life outcomes in patients with rheumatoid arthritis.

Objective: Randomised controlled trials (RCTs) have shown tocilizumab (TCZ) administered intravenously or subcutaneously with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to be superior to csDMARDs alone for improving rheumatoid arthritis (RA) disease activity. This study evaluated the effect of TCZ-intravenous and TCZ-subcutaneous on patient-reported outcomes (PROs) in three RCT populations.

Methods: OPTION (NCT00106548), BREVACTA (NCT01232569) and SUMMACTA (NCT01194414) were independent RCTs evaluating the efficacy and safety of TCZ-intravenous and/or TCZ-subcutaneous with csDMARDs in patients with RA.

Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab: Results From a Randomized, Controlled Trial.

Objective: To evaluate whether tocilizumab (TCZ) monotherapy is noninferior to treatment with TCZ plus methotrexate (MTX) for maintaining clinical responses in patients with rheumatoid arthritis (RA) in whom low disease activity is achieved with TCZ plus MTX.

Methods: Patients with RA who experienced an inadequate response to MTX received MTX plus TCZ 162 mg subcutaneously. At 24 weeks, patients who achieved a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) of ≤3.

Impact of tocilizumab monotherapy on patient-reported outcomes in patients with rheumatoid arthritis from two randomised controlled trials.

Objective: Two randomised controlled trials, AMBITION (NCT00109408) and ADACTA (NCT01119859), showed tocilizumab (TCZ) monotherapy superior to methotrexate (MTX) and adalimumab (ADA) monotherapy, respectively, for improving rheumatoid arthritis (RA) disease activity. This study compared the benefit of TCZ versus MTX or ADA monotherapy for improving patient-reported outcomes (PROs) in patients with RA.

Methods: PROs included patient global assessment (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and Short Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) and eight domain scores.

GSK-3 kinases enhance calcineurin signaling by phosphorylation of RCNs.

The conserved RCN family of proteins can bind and directly regulate calcineurin, a Ca(2+)-activated protein phosphatase involved in immunity, heart growth, muscle development, learning, and other processes. Whereas high levels of RCNs can inhibit calcineurin signaling in fungal and animal cells, RCNs can also stimulate calcineurin signaling when expressed at endogenous levels. Here we show that the stimulatory effect of yeast Rcn1 involves phosphorylation of a conserved serine residue by Mck1, a member of the GSK-3 family of protein kinases.