Ferenc Tracik

Domain-specific improvement of cognition on memantine in patients with Alzheimer's disease treated with rivastigmine.

Objective: Cholinergic therapy is used in mild-to-moderate Alzheimer’s disease (AD) and antiglutamatergic therapy in moderate-to-severe AD. Global scales, as commonly used in clinical trials, blur specifics of disease progression and drug effects. The objective was to assess combination therapy of rivastigmine plus memantine by specific neuropsychological tests in patients with mild-to-moderate AD. Methods: 12-week-short multicenter open-label pilot study. Ninety patients with mild-to-moderate AD already on stable medication with rivastigmine (3–6 mg b.i.d.) additionally received memantine for 12 weeks. Subscales of the Alzheimer’s Disease Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE) and additional neuropsychological tests (e.g. span tasks, semantic fluency) were assessed. Results: The scores in the ADAS-cog memory subscale, the MMSE score, and digit span and semantic fluency significantly improved on combination therapy. Conclusion: Memory improvement was correlated with ADAS-cog memory score at baseline and inversely with age at onset of treatment. The data suggest that improvement on combination therapy results from an improvement of attention/executive function with secondary memory improvement, which will need to be confirmed in a subsequent double-blind study on a larger number of patients.

A Double-Blind, Randomized, Placebo/Active Controlled Crossover Evaluation of the Efficacy and Safety of Ritalin® LA in Children with Attention-Deficit/Hyperactivity Disorder in a Laboratory Classroom Setting

OBJECTIVES The primary objective of this study was to demonstrate efficacy of Ritalin(®) LA 20 mg by showing superiority to placebo and noninferiority to Medikinet(®) Retard in a laboratory classroom setting. Secondary objectives included safety/tolerability and further efficacy parameters. METHODS A total of 147 children with attention-deficit/hyperactivity disorder (ADHD) diagnosed by the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and aged 6-14 (81% males) and known to be methylphenidate (MPH) responders were enrolled in this multicenter, double-blind, randomized, placebo/active-controlled, three-period (7 days each) crossover study. The Swanson, Kotlin, Agler, M-Flynn, and Pelham (SKAMP) scale was used for efficacy ratings. The mean of SKAMP Combined ratings performed at 10:30 a.m., at 12:00 a.m., and at 1:30 p.m. was defined as the primary parameter. RESULTS In all, 146 patients completed all treatment periods. Intensity and frequency of adverse events were comparable between the two formulations. Ritalin(®) LA demonstrated superiority compared to placebo (p<0.0001). The observed difference in the SKAMP scores between Ritalin(®) LA and Medikinet(®) Retard between the hours 1.5 until 4.5 did not exceed the noninferiority margin (p=0.0003); therefore, the difference is regarded as not clinically relevant. Similar results were obtained for the secondary efficacy variables. CONCLUSION Ritalin(®) LA is an efficacious, well-tolerated treatment option for children aged 6-14 with ADHD.

Effectiveness and tolerability of transdermal rivastigmine in the treatment of Alzheimer’s disease in daily practice

Background Oral cholinesterase inhibitors at doses efficacious for the treatment of Alzheimer’s disease (AD) are often prematurely discontinued due to gastrointestinal side effects. In controlled clinical trials, transdermal rivastigmine demonstrated less such effects at similar efficacy. The current study aimed to verify the validity of this data in daily practice. Methods This was a prospective, multicenter, observational study on transdermal rivastigmine in Germany. Eligible patients were those with AD who had not yet been treated with rivastigmine. Outcome measures were changes in clock-drawing test, Mini-Mental State Examination (MMSE), Caregiver Burden Scale, Clinical Global Impression (CGI), physicians’ assessments of tolerability, and the incidence of adverse events (AEs) over 4 months of treatment. Results In 257 centers 1113 patients were enrolled; 614 women and 499 men, mean age 76.5 years. In 58% of patients AD was treated for the first time and in 42% therapy was switched to transdermal rivastigmine, mostly due to lack of tolerability (13.6%) or effectiveness (26.9%). After 4 months, 67.4% of patients were on the target dose of 9.5 mg/day and 21.8% were still on 4.6 mg/day. MMSE significantly improved in patients with and without pretreatment (ΔMMSE, 0.9 ± 3.4 and 0.8 ± 3.4, respectively, both P < 0.001); the CGI score improved in 60.9% and 61.3% of patients, respectively. Overall 11.7% of patients had AEs, mainly affecting the skin or the gastrointestinal tract; in 1.1% of cases AEs were serious; 14.7% of patients discontinued therapy, 6.0% due to AEs. With rivastigmine treatment the percentage of patients taking psychotropic comedication decreased, particularly in first-time treated rivastigmine patients (from 27.1% to 22.6%; P < 0.001). Conclusion Results were in line with data from controlled clinical trials. Switching from any other oral acetylcholinesterase inhibitor to transdermal rivastigmine may improve cognition.

Fingolimod-Compassionate-use-Programm

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.

Interferon-β1b in der Multiple-Sklerose-Therapie

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. Furthermore, the following aspects will be discussed: putative mechanisms of action of interferon-β, 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-β and safety of interferon-β in children and adolescents with MS and during pregnancy.

Interferon-β1b in der Multiple-Sklerose-Therapie@@@Interferon-β1b in multiple sclerosis therapy: Mehr als 20 Jahre klinische Erfahrung@@@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. Furthermore, the following aspects will be discussed: putative mechanisms of action of interferon-β, 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-β and safety of interferon-β in children and adolescents with MS and during pregnancy.

[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. Furthermore, the following aspects will be discussed: putative mechanisms of action of interferon-β, 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-β and safety of interferon-β in children and adolescents with MS and during pregnancy.

[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. 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.

Fingolimod-Compassionate-use-Programm@@@Fingolimod compassionate use program: Fallstudie zum Konzept einer Therapieoption bei Multipler Sklerose vor Zulassung und Markteinführung@@@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. 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.

Verlauf kognitiver Störungen nach Schädel-Hirn-Trauma unter Rivastigmin

Zusammenfassung. Das Schadel-Hirn-Trauma (SHT) ist eine haufige Ursachen fur bleibende kognitive Defizite. Cholinesterase-Hemmer konnen die kognitiven Leistungen bei Alzheimer-Patienten verbessern. Um zu prufen, ob der Cholinesterase-Hemmer Rivastigmin auch die kognitiven Leistungen nach einem SHT verbessert, wurde eine doppel-blinde, placebokontrollierte Verlaufsstudie an einer Stichprobe von 66 SHT-Patienten durchgefuhrt. Die Zuordnung zwischen Rivastigmin und Placebo erfolgte randomisiert. Im Verlauf wurden neuropsychologische Standardtests aus den Bereichen Aufmerksamkeit (vier Messzeitpunkte), Lernen und Gedachtnis (zwei und drei Messzeitpunkte) sowie Exekutivfunktionen (zwei Messzeitpunkte) durchgefuhrt. Nach 20 Wochen Behandlungsdauer ergab sich kein signifikanter Unterschied zwischen der Placebo- und Experimentalgruppe. Ein tendenziell positiver Einfluss auf die kognitive Leistungsfahigkeit zu Gunsten von Rivastigmin konnte jedoch bei Patienten, deren SHT weniger als sechs Monate zurucklag, festge...