Ocrelizumab exposure in relapsing-remitting multiple sclerosis: 10-year analysis of the phase 2 randomized clinical trial and its extension.

Open-label extension (OLE) studies help inform long-term safety and efficacy of disease-modifying therapies in multiple sclerosis (MS). We report exploratory analyses from a phase 2 trial on the longest follow-up to date of ocrelizumab-treated patients with relapsing-remitting MS (RRMS). The primary treatment period (PTP) comprised four 24-week treatment cycles; participants were randomized to double-blind ocrelizumab (2000 mg or 600 mg), placebo, or interferon β-1a (open label) for one cycle, then dose-blinded ocrelizumab 1000 mg or 600 mg for the remaining cycles.

Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study.

Background: The envelope protein of human endogenous retrovirus W (HERV-W-Env) is expressed by macrophages and microglia, mediating axonal damage in chronic active MS lesions.

Objective And Methods: This phase 2, double-blind, 48-week trial in relapsing-remitting MS with 48-week extension phase assessed the efficacy and safety of temelimab; a monoclonal antibody neutralizing HERV-W-Env. The primary endpoint was the reduction of cumulative gadolinium-enhancing T1-lesions in brain magnetic resonance imaging (MRI) scans at week 24.

COVID-19 in ocrelizumab-treated people with multiple sclerosis.

Background: There are limited data on the impact of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on people with multiple sclerosis (MS).

Objective: To better understand SARS-CoV-2 infection in ocrelizumab-treated people with MS.

Methods: Internal Roche/Genentech data sources: Cases of COVID-19 from ongoing Roche/Genentech clinical trials and from post-marketing use of ocrelizumab until July 31, 2020 were identified and assessed using descriptive statistics.

Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis.

Background: Antithrombotic (anticoagulant or antiplatelet) therapy is withheld from some patients with cerebral cavernous malformations, because of uncertainty around the safety of these drugs in such patients. We aimed to establish whether antithrombotic therapy is associated with an increased risk of intracranial haemorrhage in adults with cerebral cavernous malformations.

Methods: In this population-based, cohort study, we used data from the Scottish Audit of Intracranial Vascular Malformations, which prospectively identified individuals aged 16 years and older living in Scotland who were first diagnosed with a cerebral cavernous malformation during 1999-2003 or 2006-10.

A placebo randomized controlled study to test the efficacy and safety of GNbAC1, a monoclonal antibody for the treatment of multiple sclerosis - Rationale and design.

Background: GNbAC1, a humanized monoclonal antibody, is an innovative treatment currently in development for multiple sclerosis (MS) which, contrary to the immunomodulation/immunosuppressive mechanism of action of most of the MS drugs, targets specifically a protein of endogenous retroviral origin supposed to be critical in MS pathogenesis.

Methods: This trial is a randomized placebo controlled 4-arm study with the objective of demonstrating the efficacy of repeated doses of GNbAC1 on the cumulative number of T1 Gd-enhancing lesions measured from Week 12 to 24 in patients with relapsing remitting MS (RRMS). Two hundred sixty patients with RRMS are planned to be included.

Antithrombotic therapy and bleeding risk in a prospective cohort study of patients with cerebral cavernous malformations.

Background And Purpose: Cerebral cavernous malformations (CCMs) are one of the most frequently diagnosed vascular malformations of the brain and constitute a potential source of intracranial hemorrhage. In CCM patients suffering ischemic stroke or heart disease, the use of anticoagulants or antiplatelet therapy is generally avoided by fear of hemorrhagic complications, but no systematic studies exist to support this hypothesis.

Methods: We prospectively followed-up consecutive patients with a diagnosis of one or more CCMs in a prospective database since 2008.

Short course of radiation therapy in elderly patients with glioblastoma multiforme.

Purpose: The optimal schedule of irradiation in elderly patients suffering from glioblastoma multiforme (GBM) is unsettled.

Materials And Methods: This study reviewed the charts of 28 consecutive GBM patients aged 70 years or more with a Karnofsky Performance Status (KPS) greater than or equal to 70 who received a short course of radiotherapy (40 grays in 15 fractions over three weeks).

Results: The median age at surgery was 74.

Pro- and anticoagulatory factors under sodium valproate-therapy in children.

Objective: To evaluate sodium valproate-induced hemostatic side effects in children.

Methods: A variety of both pro- and anticoagulatory parameters were longitudinally investigated in 80 children before therapy and up to 720 days after initiation of sodium valproate (VPA) therapy.

Results: VPA caused a significant reduction in platelet count (309,000/ micro l +/- 122,000 before treatment to 261,000/ micro l +/- 150,000 under VPA therapy, p = 0.

[Recommendations for blood studies and clinical monitoring in early detection of valproate-associated liver failure. Results of a consensus conferences 9 May - 11 May 1997 in Berlin].

Valproate is a frequently used antiepileptic drug. It is associated with rare but serious adverse effects like liver failure. The first symptom is impairment of the patient's well being.

[Old wine in new bottles: the "promille-killer" Party Plus].

We report about the allegedly new sobering up preparation called PARTY-PLUS, the ingredients of which resemble very much those of the inefficient "drink with a sobering up effect NEUKAMM-lemonade". In a drinking experiment Verum vs. Placebo (a light mineral water) the inefficiency of the alcohol elimination kinetics is proved once again, especially with regards to the extent of success suggested in advertising.

[The legal consequences of alcohol-induced accidents at work and in street traffic].

The publisher describes the possible problems arising, in addition to the legal consequences from an accident after alcohol consumption. The publisher refers to accidents at work or on the road during which personal injury or material damage is caused.

pNAT and CYP2D6 gene polymorphism in epileptic patients.

Certain anticonvulsant drugs require N-acetylation as a major route of metabolic clearance. Single point mutations of the polymorphic N-acetyltransferase gene (pNAT) are the primary cause for impaired drug acetylation. Pharmacokinetic parameters are altered in slow acetylator phenotypes and this may compromise drug safety.

[Anticonvulsant bromide therapy once and today].

During the past two decades, Bromides have undergone a renaissance as anticonvulsants. In this paper 6 indications for a modern bromide therapy are proposed. Guidelines referring to the concrete application of the drug, proposals concerning the dosage and any side effects are described.

[Wasted years--politics and the promille limit].

Already as early as 1955 the German Federal Board of Health pointed out that the legal treatment of drunken drivers according to traffic (criminal) law regulations was not in accord with the proven effects of alcohol upon the human system and traffic safety. The Board of Health therefore recommended a revision of the regulation. The acceptable percent of alcohol in the blood of a driver should not exceed 0.