Search results

Clinical Neuroscience

JULY 30, 2017

[Is second-line immunomodulatory treatment effective in multiple sclerosis?]

RÁCZ Lilla, BERÉNYI Ervin, BARSI Péter, BERNÁTH Dávid, CSÉPÁNY Tünde

[Purpose - Natalizumab is the first evidence based monoclonal antibody, which was launched for treatment in relapsing remitting multiple sclerosis in Hungary in 2010. Standardized follow-up is required to use it. Our aim was to evaluate the efficacy and to monitor the safety of natalizumab treatment by using an electronic database established for MS registry. Clinical activity was measured by annual relapse rates, functional status of patients measured by EDSS and MFSC. Radiological activity was evaluated by standard MRI protocol. Data, results of MS patients and side effects of natalizumab treatment were recorded in iMed software. Results - 31 patients started the natalizumab treatment after 6.5±5.8 years from the onset of MS. The efficacy of treatment was evaluated after a mean of 67 (min: 14 max: 128) infusions in December 2016. The drop-out rate was low, due to the presence of neutralising antibodies in one case, pregnancy in two cases and development of malignant disease in one case which was not related to the natalizumab treatment. The treatment was well tolerated with excellent compliance without serious side effects. The annual relapse rate reduced from a mean of 1.7 to 0.03 (p<0.000001) in the first 12 months of treatment compared to the pretreatment 12 month activity, and it stayed at low level during the whole follow up. EDSS was stable or improved with an exception of two cases. In 23 subjects (77%) lack of new/enlarging T2 lesions and lack of gadolineum-enhancing lesions on MRI were observed. 18 patients (60%) had no evidence of disease activity (NEDA-3). PASAT test improved in most of the cases. Conclusion - The natalizumab therapy was very effective in all cases including those patients who had active disease under the previous immunomodulatory treatment.]

Clinical Neuroscience

MAY 30, 2017

[Experience with natalizumab-treatment at Semmelweis University]

GOMBOS Barbara, ILJICSOV Anna, BARSI Péter, HEGEDÛS Katalin, SIMÓ Magdolna

[Multiple sclerosis is an autoimmune demyelinating disorder of the central nervous system. During the last two decades, numerous disease modifying drugs have been introduced for the treatment of the relapsing-remitting form of the disease. Since 2010, natalizumab (NTZ) treatment has been used as a second-line therapy for patients with breakthrough disease. In comparison to conventional immunomodulant drugs, NTZ has a more specific effect in that it prevents the entry of immune cells into the central nervous system without interfering with systemic immune response. The efficacy and the safety of NTZ have been confirmed by several studies. The most severe side-effect of NTZ is progressive multifocal leukoencephalopathy, which has been associated with an increased incidence in patients with anti-JCV antibody positivity, and in those who have been undergoing NTZ treatment for over two years and who have received prior immunosuppressive therapy. In the present study, our experience with natalizumab treatment of 37 patients at the Department of Neurology of Semmelweis University during the last 6 years is presented. We have observed a significant decrease of disease activity in our patients; in many cases the disease has become inactive both clinically (36/37) and radiologically (34/37). The patients’ quality of life has improved significantly during the treatment. In accordance with the literature, we confirm that NTZ is a highly effective treatment in a carefully selected patient group, and can be administered without significant inconvenience to the patient. ]

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

JULY 14, 2008

[IMMUNE-MEDIATED NEUROLOGICAL DISORDERS]

CSÉPÁNY Tünde

[Multiple sclerosis, myasthenia gravis and chronic inflammatory neuropathies share the common feature of chronic course with potential development of disability due to the damage caused by immunological processes. Early detection and precise diagnosis is very important, because most patients respond well to proper immunomodulatory treatment. The diagnosis requires extensive knowledge of the disease and is based on the clinical symptoms recognised by the GP, as well as on complex assessment of the results of special neurophysiological, radiological and laboratory examinations. The present paper reviews the major immune-mediated neurological disorders and discusses their targeted immunological treatment.]

Clinical Neuroscience

MAY 30, 2008

Clinical Neuroscience

DECEMBER 10, 2004

[Immunomodulatory treatment in multiple sclerosis ]

CSÉPÁNY Tünde, BERECZKI Dániel

[During the past decade, several disease-modifying agents have been established and have become available for the treatment of multiple sclerosis. The disease-modifying agents could be grouped into immunomodulatory and immunosuppressive therapies altering the long-term course of multiple sclerosis. Therapy is now available for relapsing-remitting, secondary progressive and progressive-relapsing multiple sclerosis. Different disease-modifying agents became also available for the treatment of relapsing-remitting multiple sclerosis in Hungary which makes the therapeutic decision difficult. This overview might help to give an answer for different questions in the management of multiple sclerosis: Which agent to choose? When to initiate the therapy? Which dose to apply? Are the drugs safe? How long to treat the patients with immunomodulatory drugs? We give a review from the literature to assess the efficacy of disease-modifying therapies and to compare the data from phase three trials of interferon β1b, two preparations of interferon β1a or glatiramer acetate for the treatment of multiple sclerosis. We analyzed the efficacy and safety of these agents on physical, inflammatory and cognitive measures of disease activity. Comparison of study results indicated similar effects of immunomodulatory agents on relapse-related and inflammatory measures in relapsing multiple sclerosis. Interferon β1a slowed the progression of disability in relapsing multiple sclerosis. One interferon β1a preparation (intramuscularly injected) demonstrated efficacy in slowing progression of cognitive dysfunction. The interferons reduced relapses at early phase of secondary progressive multiple sclerosis, but their efficacy have not yet been proven in the later phase of secondary progressive multiple sclerosis without relapses. Mitoxantrone demonstrated efficacy in slowing the progression of disability in secondary progressive multiple sclerosis. All of the disease modifying agents are safe and tolerable, if the indication is correct and the patients are strictly controlled.]

Lege Artis Medicinae

FEBRUARY 20, 2011

[Current treatment of multiple sclerosis]

CSÉPÁNY Tünde

[Multiple sclerosis (MS) is an autoimmune and degenerative disorder. In the past decades, the introduction of parenteral immunomodulatory therapies brought significant progress. These agents increase the number of relapses (shubs) by about 30%, and some of them has been shown to halter the accumulation of neurological symptoms and the development of disability. As first-line agents, interferon beta and glatiramer acetate (consisting of amino acids) can be used. Some new therapeutic strategies have been developed as a result of biotechnological development. The advantage of humanised monoclonal antibodies is that they affect the autoimmune inflammatory process more selectively. Among monoclonal antibodies, natalizumab, which binds to alpha-4-beta-1 integrin receptors and inhibits the migration of T-lymphocytes into the central nervous system, is available from February 2010 in Hungary, recommended as second-line treatment. The efficacy of natalizumab in decreasing relapse rate is >60 %. However, its use is associated with progressive multifocal leukoencephalopathy (PML) in one out of 1000 treated patient. Currently it is recommended as second-line treatment, if the patient has active disease despite immunomodulatory therapy. Among orally administered agents, a preparation containing fingolimod is expected to become available next year, and another pill, cladribin has been also found to be efficient in randomised, controlled phase III trials. Fingolimod acts on sphingosine 1-phosphate receptors- 1 (S1P1). Cladribine is a purine nucleotide analogue, and its efficacy is based on long-term reduction of CD4+ and CD8+ lymphocytes. Further promising oral immunomodulatory agents are laquinimod and BG000012 (dimethylfumarate), which are currently being tested in phase III clinical trials in relapsing-remitting MS. The most efficient treatment should be chosed on the basis of the activity, aetiology and the posited pathomechanism of the disease. With the increasing number of therapeutic options, choosing the treatment that is optimal for the patient while also considering side effects might be challenging for both the patients and physicians.]