Assessment of prolonged safety and tolerability of erenumab in migraine patients in a long-term open-label study (APOLLON).

Background: Efficacy and safety of human monoclonal antibody erenumab used for migraine prophylaxis have been shown in clinical studies. APOLLON is an open-label, multi-center, single arm study, which permits dose adjustments of erenumab and includes an option for a drug holiday. The findings contribute to the accumulating long-term evidence regarding erenumab's tolerability and safety profile in individuals experiencing episodic and chronic migraines.

Migraine patients in Germany - need for medical recognition and new preventive treatments: results from the PANORAMA survey.

Background: Migraine is a primary headache disorder characterized by recurrent attacks that may have a significant impact on patients' daily life. Treatment options must often be re-evaluated in light of efficacy, tolerability and compliance issues. Few data on commonly applied treatment algorithms and treatment failures have existed in Germany in 2017/2018.

Multiple Sclerosis Therapy With Disease-Modifying Treatments in Germany: The PEARL (ProspEctive phArmacoeconomic cohoRt evaluation) Noninterventional Study Protocol.

Background: Patients with multiple sclerosis (MS) require long-term therapy and have a wide variety of needs for health-related support. The efficacy and safety of MS therapy, as assessed by both clinicians and patients, are important parameters that need to be considered. However, few studies combine data on efficacy and safety outcomes with pharmacoeconomic data.

Acceptance of the extracare program by Beta interferon-treated patients with multiple sclerosis: results of the explore study.

Background: To gain full benefit from disease-modifying therapies such as interferon β-1b, patients with multiple sclerosis (MS) need to adhere to treatment in the long term. Treatment adherence requires high patient satisfaction with treatment and care.

Objectives: Our aim was to evaluate the satisfaction of patients with MS receiving interferon β-1b Extavia with the patient care program Extracare.

[Interferon-β1b in multiple sclerosis therapy: more than 20 years clinical experience].

The introduction of interferon-β1b in 1993 in the USA and 2 years later in Europe made it possible for the first time to alter the course of the disease in patients with relapsing-remitting multiple sclerosis (MS). Subsequently, interferon-β1b was approved for the treatment of patients with active secondary progressive MS (1999) and early relapsing-remitting MS following a first demyelinating event (clinically isolated syndrome, CIS) (2006). Here we provide an overview of the clinical experience gathered during more than 20 years of interferon-β use focusing on long-term efficacy and safety and the impact of early initiation of treatment.

[Fingolimod compassionate use program: case study on the concept of a therapy option for multiple sclerosis prior to marketing approval].

Background: In order to meet the needs of therapy of multiple sclerosis (MS) new immune therapies with a user-friendly application and better effectiveness together with good tolerability are necessary.

Compassionate Use: With respect to its potential to improve MS therapy, patients with a high medical need were given access to Fingolimod even before marketing approval. Therefore, a compassionate use program unique in the field of MS was initiated.

Randomised multicentre trial on safety and efficacy of rivastigmine in cognitively impaired multiple sclerosis patients.

Background: Cognitive decline has been recognised as a frequent symptom in multiple sclerosis (MS). Cholinesterase inhibitors (ChEIs) are employed for the treatment of Alzheimer's disease, but there is some evidence that ChEIs might also be effective in MS patients with cognitive deficits, particularly deficits of memory function.

Objective: The aim of this study was to evaluate efficacy on memory function and safety of the ChEI rivastigmine in MS patients with cognitive deficits as measured by the change from baseline of the total recall score of the selective reminding test (SRT) after 16 weeks of treatment.

B7-H1-deficiency enhances the potential of tolerogenic dendritic cells by activating CD1d-restricted type II NKT cells.

Background: Dendritic cells (DC) can act tolerogenic at a semi-mature stage by induction of protective CD4(+) T cell and NKT cell responses.

Methodology/principal Findings: Here we studied the role of the co-inhibitory molecule B7-H1 (PD-L1, CD274) on semi-mature DC that were generated from bone marrow (BM) cells of B7-H1(-/-) mice and applied to the model of Experimental Autoimmune Encephalomyelitis (EAE). Injections of B7-H1-deficient DC showed increased EAE protection as compared to wild type (WT)-DC.

The role of dendritic cells in CNS autoimmunity.

Multiple sclerosis (MS) is a chronic immune-mediated, central nervous system (CNS) demyelinating disease. Clinical and histopathological features suggest an inflammatory etiology involving resident CNS innate cells as well as invading adaptive immune cells. Encephalitogenic myelin-reactive T cells have been implicated in the initiation of an inflammatory cascade, eventually resulting in demyelination and axonal damage (the histological hallmarks of MS).

Deficiency of the negative immune regulator B7-H1 enhances inflammation and neuropathic pain after chronic constriction injury of mouse sciatic nerve.

Peripheral nerve injury induces a profound local inflammatory response that involves T cells and macrophages and augments the generation of neuropathic pain. The mechanisms underlying immune cell activation or inhibition in the peripheral nervous system, however, are unknown. The co-inhibitory molecule B7-H1 (PD-L1, CD274) attenuates immune cell proliferation and cytokine production and protects from inflammation-induced tissue damage.

Accelerated course of experimental autoimmune encephalomyelitis in PD-1-deficient central nervous system myelin mutants.

It is assumed that the onset and course of autoimmune inflammatory central nervous system (CNS) disorders (eg, multiple sclerosis) are influenced by factors that afflict immune regulation as well as CNS vulnerability. We challenged this concept experimentally by investigating how genetic alterations that affect myelin (primary oligodendrocyte damage in PLPtg mice) and/or T-cell regulation (deficiency of PD-1) influence both the onset and course of an experimental autoimmune CNS inflammatory disease [MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE)]. We observed that double pathology was associated with a significantly earlier onset of disease, a slight increase in the neurological score, an increase in the number of infiltrating cells, and enhanced axonal degeneration compared with wild-type mice and the respective, single mutant controls.

The level of B7 homologue 1 expression on brain DC is decisive for CD8 Treg cell recruitment into the CNS during EAE.

DC in the CNS have emerged as the major rate-limiting factor for immune invasion and subsequent neuroinflammation during EAE. The mechanism of how this is regulated by brain-localized DC remains unknown. Here, we describe the ability of brain-localized DC expressing B7-H1 molecules to recruit CD8(+) T cells to the site of inflammation.

Intracerebral dendritic cells critically modulate encephalitogenic versus regulatory immune responses in the CNS.

Dendritic cells (DCs) appear in higher numbers within the CNS as a consequence of inflammation associated with autoimmune disorders, such as multiple sclerosis, but the contribution of these cells to the outcome of disease is not yet clear. Here, we show that stimulatory or tolerogenic functional states of intracerebral DCs regulate the systemic activation of neuroantigen-specific T cells, the recruitment of these cells into the CNS and the onset and progression of experimental autoimmune encephalomyelitis (EAE). Intracerebral microinjection of stimulatory DCs exacerbated the onset and clinical course of EAE, accompanied with an early T-cell infiltration and a decreased proportion of regulatory FoxP3-expressing cells in the brain.

B7-H1 restricts neuroantigen-specific T cell responses and confines inflammatory CNS damage: implications for the lesion pathogenesis of multiple sclerosis.

The co-inhibitory B7-homologue 1 (B7-H1/PD-L1) influences adaptive immune responses and has been proposed to contribute to the mechanisms maintaining peripheral tolerance and limiting inflammatory damage in parenchymal organs. To understand the B7-H1/PD1 pathway in CNS inflammation, we analyzed adaptive immune responses in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced EAE and assessed the expression of B7-H1 in human CNS tissue. B7-H1(-/-) mice exhibited an accelerated disease onset and significantly exacerbated EAE severity, although absence of B7-H1 had no influence on MOG antibody production.

Modulation of T-effector function by imatinib at the level of cytokine secretion.

Objective: Recently, evidence was provided, that the selective tyrosine kinase inhibitor imatinib mesylate (imatinib) has immunomodulatory or suppressive effects. However, the discussion about imatinib's influence on immune cells is still controversial. The aim of this study was to clarify the effect of imatinib on CD8+ and CD4+ T-cell effector functions.

Expression of CD28-related costimulatory molecule and its ligand in inflammatory neuropathies.

Background: Activation of effector T lymphocytes, mediated in part by costimulatory molecules, is an important mechanism in the pathogenesis of immune-mediated diseases of the peripheral nervous system (PNS).

Objective: To analyze the expression and distribution pattern of the inducible costimulator (ICOS), a recently identified costimulatory molecule implicated in T-cell activation, and its unique ligand (ICOS-L), in inflammatory disorders of the PNS.

Methods: We studied RNA and protein expression in sural nerve biopsy specimens from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and vasculitic neuropathy (VN) vs patients with hereditary neuropathies (HNs) serving as a noninflammatory control using reverse-transcriptase PCR and immunohistochemistry.