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. The PANORAMA survey was designed to explore and characterize the migraine healthcare landscape and to demonstrate the medical treatment need at that time in Germany. METHODS: Three different questionnaires were used to assess the profile of the 119 participating centers, characterize migraine patients at centers and evaluate qualitative aspects of the current migraine healthcare situation from a physician´s professional perspective. Data were analyzed as observed and summarized by descriptive statistics. RESULTS: The results demonstrate that once referred to a migraine specialist, the majority of patients continue to be treated at a specialist. At specialized centers, 41.6 % of migraine patients receive prophylactic treatment. 45.4 % of prophylactic treatments are initiated with a beta-blocker and 28.1 % with an anti-epileptic. Pivotal factors to initiate prophylactic treatment are migraine attack frequency and intensity (58.0 %). Treatment decisions are largely based on prior / concomitant diseases and physical constitution of the patient (52.1 %). Following an inadequate treatment, most patients either switch substance class or discontinue prophylactic treatment. CONCLUSIONS: PANORAMA gives a comprehensive overview of the migraine healthcare landscape in Germany in 2017/2018, elucidates a lack of common treatment algorithms and reveals a high demand for defined therapy strategies and new prophylactic treatment going forwards.

[Interferon-ß1b in multiple sclerosis therapy: more than 20 years clinical experience]. / Interferon-ß1b in der Multiple-Sklerose-Therapie : Mehr als 20 Jahre klinische Erfahrung.

The introduction of interferon-ß1b 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-ß1b 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-ß use focusing on long-term efficacy and safety and the impact of early initiation of treatment. Furthermore, the following aspects will be discussed: putative mechanisms of action of interferon-ß, indications for a disease-modifying therapy, clinical relevance of neutralizing antibodies, importance of adherence in MS therapy, high versus low frequency therapy, combination therapies with interferon-ß and safety of interferon-ß in children and adolescents with MS and during pregnancy.

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. METHODS: Efficacy and safety of rivastigmine were analysed in a 16-week, multicentre, double-blind, randomised, placebo-controlled study, followed by an optional one-year open-label treatment phase. Effects of rivastigmine and placebo were compared by an analysis of covariance. RESULTS: In total, 86 patients were enrolled. Patients who received rivastigmine (n = 43) showed a non-significant increase in total recall score (sum of all words immediately recalled over all six trials) over placebo (n = 38) after 16 weeks of treatment (p = 0.2576). Other outcome measures provided no evidence supporting benefits of rivastigmine. Treatment with rivastigmine was well tolerated. CONCLUSIONS: With the results of this study, the need for an effective therapy in cognitively impaired MS patients is still required. Thus, intensive and continued clinical research is required to explore therapeutic options for cognitive deficits in MS patients.

[Fingolimod compassionate use program: case study on the concept of a therapy option for multiple sclerosis prior to marketing approval]. / Fingolimod-Compassionate-use-Programm : Fallstudie zum Konzept einer Therapieoption bei Multipler Sklerose vor Zulassung und Markteinführung.

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. In total 137 centers participated (75 % outpatient neurologists and 25 % hospitals). Within 19 weeks 135 patients were enrolled to receive Fingolimod. The patients in the compassionate use program can be representatively described as showing hardly controllable disease activity and progression with currently available, often poorly tolerated therapy. The compassionate use program for these patients offered better control of the disease with Fingolimod. The adverse events were as expected. CONCLUSIONS: The Fingolimod compassionate use program demonstrated the need for this new therapeutic option. Patients who were not yet sufficiently treated were provided with an effective therapy with a good safety profile and a user-friendly administration form.

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. In addition, in vitro analysis was performed by flow cytometry. RESULTS: ICOS and ICOS-L mRNA was found to be significantly upregulated in samples from patients with GBS, CIDP, and VN compared to HNs. Immunohistochemistry identified T lymphocytes as the cellular source of ICOS, whereas macrophages expressed the corresponding ligand ICOS-L. Further analysis revealed that the distribution of ICOS-expressing T cells did not differ between acute and chronic inflamed PNS diseases. Correspondingly, the expression pattern of ICOS-L was similar in the inflamed tissues but differed significantly when compared to HNs. CONCLUSIONS: Inducible costimulator, expressed by T lymphocytes, and inducible costimulator ligand, expressed by macrophages within the peripheral nerve, might not only be relevant in inducing an acute immune response but might also be critically involved in perpetuating inflammation in chronically immune-mediated disorders of the peripheral nervous system.