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Clinical Neuroscience

NOVEMBER 30, 2017

[Role of peginterferon-β-1a in the therapy of multiplex sclerosis]

SIMÓ Magdolna, ILJICSOV Anna

[The subcutaneous peginterferon-b-1a is recently introduced in the therapy of relapsing-remitting multiplex sclerosis (RRMS) patients. Pegylation of IFN b-1a improved pharmacodynamic and pharmacokinetic properties, resulting in, increased biologic activity and a longer half-life. The efficacy of peginterferon-b-1a was proved by the ADVANCE study - a 2-year Phase 3, multicenter, randomized, double-blind study with a 1-year placebocontrolled period evaluating the efficacy and safety of subcutaneous peginterferon-b-1a administered every 2 or 4 weeks in patients with RRMS. Peginterferon-b-1a efficacy was maintained during the two years, with greater effects observed with every 2 week versus every 4 week dosing. Annualized relapse rate and confirmed disability progression was reduced comparing with patients on delayed treatment. Patients treated with continuous peginterferon-b-1a had fewer new or newly enlarging T2 lesions over 2 years than patients in the delayed treatment group. Adverse events were consistent with the known profiles of IFN b therapies in MS. The most commonly reported adverse events were injection site erythema, influenza-like illness. The less frequent administration is associated with fewer flu-like adverse events, which may improve patients’ compliance and adherence. Peginter-feron-b-1a could be an effective and safe treatment option for RRMS patients.]

Clinical Neuroscience

NOVEMBER 30, 2017

[Alemtuzumab therapy 2017]

BIERNACKI Tamás, BENCSIK Krisztina, SANDI Dániel, VÉCSEI László

[Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system comprising of inflammation, demyelinisation and neurodegeneration. The natural history of MS is heterogenous. Owing to the vast range and severity of the symptoms MS can cause the effect of the disease on one’s cognitive and physical status is unpredictable. According to the new, phenotype based classification two subgroups can be distinguished; relapsing-remitting (RR) and progressive MS. Relapsing-remitting MS can be further divided into active and inactive disease. The activity of the disease can be proven either clinically and/or by radiological means. A patient’s disease is considered inactive, if it fulfills the criteriae set in the “no evidence of disease activity-3” (NEDA-3) concept, meaning that no progression can be seen on the MRI scans, the patient is relapse free and there is no worsening on any disability scale. Nowadays a paradigm shift can be seen in the treatment of MS. The aim of this shift is to provide each and every patient with the most potent medication best suiting his/her illness as soon as possible. Alemtuzumab offers a great option as either a first line treatment or as escalation therapy for patients with a highly active disease. The efficacy of alemtuzumab was proven in two phase III trials (CARE-MS I, II), where it was compared to subcutaneous interferon b-1a, administered three times weekly. In both studies alemtuzumab was superior to subcutaneous interferon b-1a in terms of relapse rate reduction, in all scouted MRI parameters. In the CARE-MS II trial it was found superior in terms of progression slowing. In the studies’ first 2 years 32% and 39% of the alemtuzumab treated patients managed to achieve the NEDA-3 state (data from CARE-MS II and I respectively). At the end of the 4 year extension of both studies these numbers have increased to 60% and 55% respectively. The aim of our synopsis is to suggest neurologists an evidence based guideline, a therapeutic algorithm to be used when they give their MS patients the very best, personalised treatment, and also to appoint the recently introduced alemtuzumab to its proper place in the algorithm.]

Clinical Neuroscience

MAY 30, 2015

[Alemtuzumab: benefits and challenges of new therapy in multiple sclerosis]

ILLÉS Zsolt, TOBIAS Sejbaek, CSÉPÁNY Tünde

[The widening spectrum of MS treatment is partially due to increasing knowledge about the pathogenesis of MS. The humanized monoclonal antibody against CD52, alemtuzumab has been approved in Europe for the treatment of MS, which results in long-term depletion of B and T cells due to complement- and antibody-mediated cytotoxicity. Based on phase 2 and 3 clinical trials, alemtuzumab decreases the risk of sustained neurological deficit and progression compared to high-dose subcutaneous interferon- β1a in patients with active relapsing-remitting MS, either treatment-naïve or with breakthrough disease. We review advantages and benefits of the treatment, discuss safety concerns, and present a case to describe practical issues.]

Clinical Neuroscience

MARCH 25, 2015

[Teriflunomide: new oral immunmodulant drug in therapy of multiple sclerosis]

BENCSIK Krisztina, RÓZSA Csilla, VÉCSEI László

[Multiple sclerosis (MS) is the autoimmune, demyelinating, neurodegenerative disorder of the central nervous system (CNS). There are nine drugs available in Hungary reimbursed by the National Health Insurance Fund of Hungary (OEP) to reduce the activity of the disease, from which seven can be used as first line therapies. We have approximately 20 years of experience with the interferon b-1a/1b and glatiramer-acetate products. Though in case of approximately 30% of the patients using one of the first line drugs, the disease remains active, that we call break-through disease. The reasons for break-through disease could be the insufficient adherence and compliance, the appearance of neutralizing antibodies or the high activity of the disease. One of the oral immunomodulating drugs for MS, teriflunomide, was registered in Europe in 2013. Because of the anti-proliferative and anti-inflammatory effect of teriflunomide, it can be used for the reduction of the disease activity in the relapsing-remitting course of MS. The effect of teriflunomide was proved in one Phase II. and four Phase III. (TEMSO, TOWER, TENERE, TOPIC) studies. Teriflunomide 14 mg once daily was able to demonstrate in two consecutive placebo-controlled phase 3 clinical trials that significantly reduces the relapse rate (31.5% and 36.3%) and in both studies significantly reduces the sustained disability progression (29.8% and 31.5%) moreover delays the appearance of the clinically definitive MS in patients with clinically isolated syndrome (CIS). According to the TENERE study there were no significant differences observed between teriflunomide 14 mg and IFNb-1a s.c. in time to failure and annualized relapse rate but the treatment satisfaction domains of global satisfaction, side-effects and convenience were significantly improved with teriflunomide compared with s.c. IFNb-1a. ]

LAM Extra for General Practicioners

FEBRUARY 20, 2015

[Treatment of hepatits C virus infected patients with cirrhosis in real-life conditions in Hungary with the two pegylated interferons]

[AIMS - In this trial we have analyzed the data of cirrhotic naiv as well as treatment experienced patients with chronic hepatitis C, treated in the East-Hungarian hepatology centers, between 2004 and 2010, because in the era of triple combinations, we mostly treat cirrhotic patients. PATIENTS AND METHODS - We have found 272 patients and in most of them the cirrhosis was proven by biopsy. These patients were treated with pegylated interferon (pegIFN) alpha plus ribavirin in combination, 172 were naiv and 100 patients were treatment experienced. Data were collected retrospectively and the pretreatment parameters like age, sex, body weight, transaminase level, genotype, initial viral load, comorbidities, and proportion of first and repeated treatments have been analyzed. We have investigated the influence of the initial parameters as well as the type of pegIFN on the complete early virologic response (cEVR) and on the sustained virological response (SVR). RESULTS - The cEVR was 27% (74/272) and the SVR was 21% (58/272) in the whole patient population. With pegIFN a-2a, 32% (45/141) cEVR and 28% (39/141) SVR, whereas with pegIFN a-2b 22% (29/131) cEVR and 15% (19/131) SVR were achieved. Among this patient population the largest subgroup was the naiv patients with high viral load (HVL). In this subgroup the SVR was 21% (28/132). However, with pegIFN a-2a SVR was 29% (21/73), whereas with pegIFN a-2b SVR was only 12% (7/59). The above differences found between the two pegIFNs proved to be statistically significant. Age <40 years, low viral load (LVL) and treatment with pegIFN a-2a proved to be independent positive factors influencing cEVR as well as SVR, by multiple logistic regression analysis. CONCLUSION - According to these results, cirrhotic patients with hepatitis C may benefit if pegIFN a-2a is used as backbone therapy in triple combinations. ]

Lege Artis Medicinae

DECEMBER 20, 2014

[Treatment of hepatits C virus infected patients with cirrhosis in real-life conditions in Hungary with the two pegylated interferons]

[AIMS - In this trial we have analyzed the data of cirrhotic naiv as well as treatment experienced patients with chronic hepatitis C, treated in the East-Hungarian hepatology centers, between 2004 and 2010, because in the era of triple combinations, we mostly treat cirrhotic patients. PATIENTS AND METHODS - We have found 272 patients and in most of them the cirrhosis was proven by biopsy. These patients were treated with pegylated interferon (pegIFN) alpha plus ribavirin in combination, 172 were naiv and 100 patients were treatment experienced. Data were collected retrospectively and the pretreatment parameters like age, sex, body weight, transaminase level, genotype, initial viral load, comorbidities, and proportion of first and repeated treatments have been analyzed. We have investigated the influence of the initial parameters as well as the type of pegIFN on the complete early virologic response (cEVR) and on the sustained virological response (SVR). RESULTS - The cEVR was 27% (74/272) and the SVR was 21% (58/272) in the whole patient population. With pegIFN a-2a, 32% (45/141) cEVR and 28% (39/141) SVR, whereas with pegIFN a-2b 22% (29/131) cEVR and 15% (19/131) SVR were achieved. Among this patient population the largest subgroup was the naiv patients with high viral load (HVL). In this subgroup the SVR was 21% (28/132). However, with pegIFN a-2a SVR was 29% (21/73), whereas with pegIFN a-2b SVR was only 12% (7/59). The above differences found between the two pegIFNs proved to be statistically significant. Age <40 years, low viral load (LVL) and treatment with pegIFN a-2a proved to be independent positive factors influencing cEVR as well as SVR, by multiple logistic regression analysis. CONCLUSION - According to these results, cirrhotic patients with hepatitis C may benefit if pegIFN a-2a is used as backbone therapy in triple combinations. ]

Clinical Neuroscience

JULY 30, 2014

[Natalizumab therapy, 2013]

KARÁCSONY Mária, BENCSIK Krisztina, VÉCSEI László

[Multiple sclerosis (MS) is the most common chronic disease of the central nervous system in young adults. No curative therapy is known. Currently, six drugs are available that can reduce the activity of MS. The first-line drugs can completely reduce the activity of the disease in nearly two-thirds of the patients. In the remainder, who suffer from breakthrough disease, the condition of the patient worsens, and secondline therapies must be used. The second-line drug natalizumab exhibits almost double efficacy of the first-line drugs, but also have less favourable adverse effects. As a severe side-effect for instance, natalizumab carries the risk of the development of progressive multifocal leucoencephalopathy (PML), caused by a polyoma virus, the JC virus. There are three major risk factors for PML: an anti-JCV antibody status, a long duration of natalizumab treatment and prior immunosuppressant therapy. The lowest-risk group (1:14 286) comprises of patients who are anti-JCV antibody-negative, in whom the prior immunosuppressant use and duration of natalizumab therapy do not influence the risk of PML. With no prior immunosuppressant treatment, the incidence of PML increases to 1 in 192 patients after 2 years among those who are anti-JCV antibody-positive. These data may lead the physician to decide to discontinue natalizumab treatment. The half-life of natalizumab is three months; during this time other therapies can not be administered and the patients encounter the rebound effect: as the patients receiving natalizumab therapy displayed a high disease activity before treatment, the rebound effect can lead to relapses. After the termination of natalizumab secondline disease-modifying therapy with fingolimod may be introduce; no PML cases occur in response to fingolimod treatment. In the large majority of patients taking natalizumab who do not develop PML, this drug is highly effective and can prevent the progression of MS. The benefit of therapy and the risk of PML must be considered on an individual basis, with regard to the disease activity, the progression and the MRI activity, before natalizumab therapy is implemented.]

Lege Artis Medicinae

MARCH 20, 2014

[The role of hepatitis C virus in the development of non-Hodgkin lymphomas]

SULYOK Mihály, MAKARA Mihály, ÚJHELYI Eszter, VÁLYI-NAGY István

[There is a growing body of evidence for the association between chronic hepatitis C virus infection and certain subtypes of Bcell non-Hodgkin lymphoma. The development of a lymphoid malignancy is usually preceded by cryoglobulinaemia. Here, we summarise the most important epidemiologic data, and the possible molecular mechanisms of HCV-associated lymphomagenesis. The direct oncogenic effect of the virus has not been proven, but chronic antigenic stimulation maintained by replication and viral lymphotropism might both contribute to the development of lymphomas. It should be emphasised that elimination of the hepatitis C virus can halt this process in case of cryoglobulinaemia and low-grade malignity (usually marginal zone lymphomas). In these cases, antiviral therapy might be a useful alternative of conventional immune-chemotherapy. Thus, a collaboration between haematologists and hepatologists might be a great step forward in the treatment of these diseases. It is still not established whether interferon-based short-course therapies and interferon-free regimens are also effective in the treatment of associated lymphomas.]