Low immunogenicity of tocilizumab in patients with rheumatoid arthritis

Objective Subcutaneous (SC) and intravenous formulations of tocilizumab (TCZ) are available for the treatment of patients with rheumatoid arthritis (RA), based on the efficacy and safety observed in clinical trials. Anti-TCZ antibody development and its impact on safety and efficacy were evaluated in adult patients with RA treated with intravenous TCZ (TCZ-IV) or TCZ-SC as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Methods Data from 5 TCZ-SC and 8 TCZ-IV phase III clinical trials and 1 TCZ-IV clinical pharmacology safety study (>50 000 samples) were pooled to assess the immunogenicity profile of TCZ-SC and TCZ-IV (8974 total patients). The analysis included antidrug antibody (ADA) measurement following TCZ-SC or TCZ-IV treatment as monotherapy or in combination with csDMARDs, after dosing interruptions or in TCZ-washout samples, and the correlation of ADAs with clinical response, adverse events or pharmacokinetics (PK). Results The proportion of patients who developed ADAs following TCZ-SC or TCZ-IV treatment was 1.5% and 1.2%, respectively. ADA development was also comparable between patients who received TCZ monotherapy and those who received concomitant csDMARDs (0.7–2.0%). ADA development did not correlate with PK or safety events, including anaphylaxis, hypersensitivity or injection-site reactions, and no patients who developed ADAs had loss of efficacy. Conclusions The immunogenicity risk of TCZ-SC and TCZ-IV treatment was low, either as monotherapy or in combination with csDMARDs. Anti-TCZ antibodies developed among the small proportion of patients had no evident impact on PK, efficacy or safety

Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

Background: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. Methods: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. Conclusions: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.

Visual Impairment in Patients with Giant Cell Arteritis Treated with Tocilizumab in Real-World Clinical Practice

The GiACTA trial demonstrated the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) [1]. However, the effectiveness of TCZ for prevention of specific GCA-related visual manifestations is currently unknown. The incidence of GCA-related visual manifestations was analyzed in patients treated with TCZ in a real-world setting

Visual Impairment in Patients with Giant Cell Arteritis Treated with Tocilizumab in Real-World Clinical Practice

The GiACTA trial demonstrated the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) [1]. However, the effectiveness of TCZ for prevention of specific GCA-related visual manifestations is currently unknown. The incidence of GCA-related visual manifestations was analyzed in patients treated with TCZ in a real-world setting

Visual Impairment in Patients with Giant Cell Arteritis Treated with Tocilizumab in Real-World Clinical Practice

The GiACTA trial demonstrated the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) [1]. However, the effectiveness of TCZ for prevention of specific GCA-related visual manifestations is currently unknown. The incidence of GCA-related visual manifestations was analyzed in patients treated with TCZ in a real-world setting

Concomitant Use of Statins in Tocilizumab-Treated Patients with Rheumatoid Arthritis: A Post Hoc Analysis

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s40744-016-0049-8">https://link.springer.com/article/10.1007/s40744-016-0049-8</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

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

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

A scalable polymer-free method for transferring graphene onto arbitrary surfaces

An efficient and reliable transfer for graphene onto the substrates of interests acts as the crucial bridge between the graphene synthesis and applications. The main reason that this issue has not been fully addressed is the use of a polymer medium to protect the one-atom-thick material during the transfer process. Here we demonstrate a general and scalable method to transfer chemical-vapor-deposited graphene onto arbitrary surfaces without any polymers, which yields the transfer of macroscopically and microscopically clean, continuous and uniform graphene samples onto a wide variety of substrates, as well as the scalable layer-by-layer graphene epitaxial structures. Moreover, the transferred graphene exhibits an overall 100% enhancement in the electrical conductivity compared with the conventional method, so that various high-performance flexible transparent electrodes can be demonstrated. We believe that this new transfer technique will offer the opportunities to the industrialization of next generations of flexible electronics and other graphene-based disruptive technologies. (C) 2020 Elsevier Ltd. All rights reserved

Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial

F. Hoffmann La-Roche Ltd, Basel, Switzerlan