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https://www.readbyqxmd.com/read/28804651/pharmacogenetic-biomarkers-to-predict-treatment-response-in-multiple-sclerosis-current-and-future-perspectives
#1
REVIEW
Patricia K Coyle
Disease-modifying therapies (DMTs) have significantly advanced the treatment of relapsing multiple sclerosis (MS), decreasing the frequency of relapses, disability, and magnetic resonance imaging lesion formation. However, patients' responses to and tolerability of DMTs vary considerably, creating an unmet need for biomarkers to identify likely responders and/or those who may have treatment-limiting adverse reactions. Most studies in MS have focused on the identification of pharmacogenetic markers, using either the candidate-gene approach, which requires prior knowledge of the genetic marker and its role in the target disease, or genome-wide association, which examines multiple genetic variants, typically single nucleotide polymorphisms (SNPs)...
2017: Multiple Sclerosis International
https://www.readbyqxmd.com/read/28770366/management-of-pregnancy-related-issues-in-multiple-sclerosis-patients-the-need-for-an-interdisciplinary-approach
#2
Maria Pia Amato, Antonio Bertolotto, Roberto Brunelli, Paola Cavalla, Benedetta Goretti, Maria Giovanna Marrosu, Francesco Patti, Carlo Pozzilli, Leandro Provinciali, Nicola Rizzo, Nicola Strobelt, Gioacchino Tedeschi, Maria Trojano, Giancarlo Comi
Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS), most probably autoimmune in origin, usually occurring in young adults with a female/male prevalence of approximately 3:1. Women with MS in the reproductive age may face challenging issues in reconciling the desire for parenthood with their condition, owing to the possible influence both on the ongoing or planned treatment with the possible consequences on the disease course and on the potential negative effects of treatments on foetal and pregnancy outcomes...
August 2, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28762192/a-comprehensive-review-on-copemyl-%C3%A2
#3
REVIEW
Pietro Annovazzi, Antonio Bertolotto, Vincenzo Brescia Morra, Claudio Gasperini, Enrico Montanari, Pierluigi Navarra, Francesco Patti, Maria Pia Sormani, Angelo Ghezzi
Economic sustainability is of paramount importance in the rapidly evolving therapeutic scenario of multiple sclerosis (MS). Glatiramoids are a class of drugs whose forefather, glatiramer acetate, has been used as a disease modifying drug (DMD) in patients with MS for over 20 years. Its patent expired in 2015; new versions of such drug are nowadays available on the market, potentially contributing to lowering prices and enhancing a better allocation of economic resources. In this review, we analyze the recommendations underlying the approval of both generic drugs and biosimilars by regulatory authorities, and we provide methodological tools to contextualize the design of studies on these new classes of drugs...
July 31, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28751099/efficacy-and-safety-of-delayed-release-dimethyl-fumarate-for-relapsing-remitting-multiple-sclerosis-in-prior-interferon-users-an-integrated-analysis-of-define-and-confirm
#4
Óscar Fernández, Gavin Giovannoni, Robert J Fox, Ralf Gold, J Theodore Phillips, James Potts, Macaulay Okwuokenye, Jing L Marantz
PURPOSE: In Phase III studies (DEFINE [Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting MS]/CONFIRM [Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis]), delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). Post hoc analyses of integrated data from DEFINE/CONFIRM were conducted to evaluate the effect of DMF in patients previously treated with interferon (IFN) beta...
July 24, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28721023/persistence-to-disease-modifying-therapies-for-multiple-sclerosis-in-a-canadian-cohort
#5
Dessalegn Y Melesse, Ruth Ann Marrie, James F Blanchard, Bo Nancy Yu, Charity Evans
PURPOSE: To examine the long-term persistence to the first-line injectable disease-modifying therapies (DMTs) for multiple sclerosis (MS) and to identify the factors associated with nonpersistence. PATIENTS AND METHODS: We used population-based administrative data from Manitoba, Canada. All adult subjects who were diagnosed with MS and dispensed a first-line injectable DMT (beta-interferon-1b, beta-interferon-1a, and glatiramer acetate) between 1996 and 2011 and had a minimum of 1 year of follow-up were included...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28706565/once-daily-glatiramer-acetate-decreases-magnetic-resonance-imaging-disease-activity-in-japanese-patients-with-relapsing-remitting-multiple-sclerosis
#6
Takashi Yamamura, Natalia Ashtamker, David Ladkani, Toshiyuki Fukazawa, Hideki Houzen, Masami Tanaka, Toshiro Miura, Volker Knappertz
OBJECTIVE: Multiple sclerosis (MS) prevalence, clinical patterns, and treatment responses vary between races and geographical latitudes. Glatiramer acetate (GA; Copaxone) has provided a safe, effective treatment option for relapsing-remitting MS patients in the USA, European nations, and other countries for decades. The objective of the present study was to assess the safety and efficacy of GA in reducing magnetic resonance imaging disease activity in Japanese patients with active relapsing-remitting MS...
May 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/28689102/monthly-methylprednisolone-in-combination-with-interferon-beta-or-glatiramer-acetate-for-relapsing-remitting-multiple-sclerosis-a-multicentre-single-blind-prospective-trial
#7
Serkan Ozakbas, Bilge Piri Cinar, Gorkem Kosehasanoğullari, Turhan Kahraman, Didem Oz, Behice Bircan Kursun
OBJECTIVES: Multiple sclerosis is usually clinically characterized by repeated subacute relapses followed by remissions. Corticosteroids are used for relapses, and this treatment has been shown to increase the speed of recovery from these. We aimed to evaluate the efficacy and safety of pulsed methylprednisolone given every month as an add-on therapy to interferon beta or glatiramer acetate in patients with relapsing-remitting multiple sclerosis. PATIENTS AND METHODS: This was a multi-center, examiner-blinded, prospective study...
September 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28686222/multiple-sclerosis-immunopathology-and-treatment-update
#8
REVIEW
Narges Dargahi, Maria Katsara, Theodore Tselios, Maria-Eleni Androutsou, Maximilian de Courten, John Matsoukas, Vasso Apostolopoulos
The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year...
July 7, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28680308/clinical-radiological-and-electrophysiological-comparison-of-immunomodulatory-therapies-in-multiple-sclerosis
#9
Gençer Genç, Şeref Demirkaya, Semai Bek, Zeki Odabaşi
INTRODUCTION: Although it has been shown that immunomodulatory therapies (IMTs) in multiple sclerosis (MS) can modify the course of the disease by reducing the relapse rate and delaying the progression of disability, no study comparing IMTs head-to-head in terms of clinical, radiological, and electrophysiological changes is available. We aimed to investigate the effects of interferon-beta (IFN-B) 1b, IFN-B-1a subcutaneous (sc), IFN-B-1a intramuscular (im), and glatiramer acetate (GA) therapies on clinical, electrophysiological, and radiological findings...
June 2017: Noro Psikiyatri Arsivi
https://www.readbyqxmd.com/read/28649912/comparative-effectiveness-of-rituximab-relative-to-ifn-%C3%AE-or-glatiramer-acetate-in-relapsing-remitting-ms-from-the-swedish-ms-registry
#10
Tim Spelman, Thomas Frisell, Fredrik Piehl, Jan Hillert
OBJECTIVE: To compare treatment effectiveness and persistence in relapsing-remitting multiple sclerosis patients who initiated rituximab versus glatiramer acetate (GA) or interferon-beta (IFN-β). METHODS: A total of 461 patients from the Swedish MS registry in the rituximab arm were propensity score matched on a 1:2 basis with 922 patients from the IFN-β/GA comparator, between April 2005 and November 2015. Annualised relapse rate (ARR) was compared using the Poisson method...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28642148/biological-activity-of-glatiramer-acetate-on-treg-and-anti-inflammatory-monocytes-persists-for-more-than-10years-in-responder-multiple-sclerosis-patients
#11
Michela Spadaro, Francesca Montarolo, Simona Perga, Serena Martire, Federica Brescia, Simona Malucchi, Antonio Bertolotto
Glatiramer acetate (GA) is a widely used treatment for multiple sclerosis (MS), with incompletely defined mechanism of action. Short-term studies suggested its involvement in the modulation of anti-inflammatory cytokines and regulatory T cells (Treg), while long-term effect is still unknown. To investigate this aspect, we analyzed by flow-cytometry peripheral-blood Treg, natural killer (NK), CD4 and CD8 T-cells and anti-inflammatory CD14(+)CD163(+) monocytes from 37 healthy donor and 90 RRMS patients divided in untreated, treated with GA for 12months and from 34 to 192months...
June 19, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28617366/-an-effect-of-disease-modifying-drugs-on-the-development-of-children-born-to-mothers-with-multiple-sclerosis
#12
D S Kasatkin, N N Spirin, T V Vinogradova, A S Shytova
AIM: To evaluate an effect of mother's treatment with disease-modifying drugs (DMD) on the mental and physical development of the child in the first year of life. MATERIAL AND METHODS: Thirty pregnancies resulted in birth of live babies in patients with multiple sclerosis (MS) were studied. The diagnosis of MS was made to the mother before conception of the child. Seven mothers did not receive DMD at the moment of conception (controls), 13 mother were treated with interferon-beta (IFN) and 10 with glatiramer acetate...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28607752/enhanced-disease-reduction-using-clozapine-an-atypical-antipsychotic-agent-and-glatiramer-acetate-combination-therapy-in-experimental-autoimmune-encephalomyelitis
#13
Laura K Green, Pirooz Zareie, Nikki Templeton, Robert A Keyzers, Bronwen Connor, Anne Camille La Flamme
BACKGROUND: Atypical antipsychotic agents (AAP) alleviate the symptoms of severe mental health disorders, such as schizophrenia, by antagonizing dopamine and serotonin receptors. Recently, AAP have also been shown to exhibit immunomodulatory properties in the central nervous system (CNS). OBJECTIVE: Building on research which demonstrated the ability of the AAP risperidone and clozapine to modify the disease course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we aimed to more fully investigate the potential of clozapine as a possible treatment for MS...
January 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/28603463/case-report-two-cases-of-nicolau-syndrome-associated-with-glatiramer-acetate
#14
Dorlan J Kimbrough, Scott D Newsome
We report two cases of Nicolau syndrome (embolia cutis medicamentosa), a rare complication of injectable medications, both associated with the administration of 20 mg of subcutaneous glatiramer acetate. Both patients required surgical debridement and were subsequently treated conservatively without additional complications. Patient 1 opted to discontinue disease-modifying therapy. Patient 2 continued glatiramer acetate therapy without complications by using other injection sites. These cases highlight the need for prompt investigation of new unusual skin lesions in patients receiving injectable multiple sclerosis treatments (regardless of length of treatment and previous minor cosmetic concerns) and illustrate the clinical distinction between Nicolau syndrome and drug-induced skin necrosis...
May 2017: International Journal of MS Care
https://www.readbyqxmd.com/read/28572277/immunotherapies-in-neuromyelitis-optica-spectrum-disorder-efficacy-and-predictors-of-response
#15
MULTICENTER STUDY
Jan-Patrick Stellmann, Markus Krumbholz, Tim Friede, Anna Gahlen, Nadja Borisow, Katrin Fischer, Kerstin Hellwig, Florence Pache, Klemens Ruprecht, Joachim Havla, Tania Kümpfel, Orhan Aktas, Hans-Peter Hartung, Marius Ringelstein, Christian Geis, Christoph Kleinschnitz, Achim Berthele, Bernhard Hemmer, Klemens Angstwurm, Kim Lea Young, Simon Schuster, Martin Stangel, Florian Lauda, Hayrettin Tumani, Christoph Mayer, Lena Zeltner, Ulf Ziemann, Ralf Andreas Linker, Matthias Schwab, Martin Marziniak, Florian Then Bergh, Ulrich Hofstadt-van Oy, Oliver Neuhaus, Uwe Zettl, Jürgen Faiss, Brigitte Wildemann, Friedemann Paul, Sven Jarius, Corinna Trebst, Ingo Kleiter
OBJECTIVE: To analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD). DESIGN: This is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes...
August 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28537110/three-year-clinical-outcomes-of-relapsing-multiple-sclerosis-patients-treated-with-dimethyl-fumarate-in-a-united-states-community-health-center
#16
Kyle Smoot, Kateri J Spinelli, Tamela Stuchiner, Lindsay Lucas, Chiayi Chen, Lois Grote, Elizabeth Baraban, Kiren Kresa-Reahl, Stanley Cohan
BACKGROUND: Following approval of dimethyl fumarate (DMF), we established a registry of relapsing multiple sclerosis (RMS) patients taking DMF at our community MS center. OBJECTIVE: To track DMF patients' tolerability, disease progression, and lymphopenia. METHODS: Patients prescribed DMF for RMS from March 2013 to March 2016 were prospectively enrolled ( N = 412). Baseline data, clinical relapses, magnetic resonance imaging (MRI) activity, discontinuation, and lymphocyte counts were captured through chart review...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28530523/cost-effectiveness-of-peginterferon-beta-1a-and-alemtuzumab-in-relapsing-remitting-multiple-sclerosis
#17
Ankur A Dashputre, Khalid M Kamal, Gauri Pawar
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, affecting 2.5 million people globally and 400,000 people in the United States. While no cure exists for MS, the goal is to manage the disease using disease-modifying therapies (DMTs), which have been shown to slow disease progression and prevent relapses. Relapsing-remitting MS (RRMS) is the most common form of MS at the time of diagnosis. Peginterferon beta-1a (PEG) and alemtuzumab (ALT) were recently approved and have demonstrated good clinical outcomes, including reduced relapse rates in clinical trials...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28475587/two-studies-in-one-a-propensity-score-matched-comparison-of-fingolimod-versus-interferons-and-glatiramer-acetate-using-real-world-data-from-the-independent-german-studies-pangaea-and-pearl
#18
Jonathan Alsop, Jennie Medin, Christian Cornelissen, Stefan Viktor Vormfelde, Tjalf Ziemssen
BACKGROUND: This study compared outcomes following fingolimod or BRACE treatments (beta-interferons/glatiramer acetate) in patients with active MS (≥ 1 relapse in the previous year) following previous BRACE treatment. METHODS AND FINDINGS: Patients with active MS who previously received BRACE were identified from German prospective, observational studies, PANGAEA and PEARL. A novel methodology was developed to compare outcomes between propensity-score-matched cohorts (3:1 ratio) from the independent single-arm studies...
2017: PloS One
https://www.readbyqxmd.com/read/28458668/the-multiple-sclerosis-ms-genetic-risk-factors-indicate-both-acquired-and-innate-immune-cell-subsets-contribute-to-ms-pathogenesis-and-identify-novel-therapeutic-opportunities
#19
REVIEW
Grant P Parnell, David R Booth
Multiple sclerosis (MS) is known to be a partially heritable autoimmune disease. The risk of developing MS increases from typically 1 in 1,000 in the normal population to 1 in 4 or so for identical twins where one twin is affected. Much of this heritability is now explained and is due almost entirely to genes affecting the immune response. The largest and first identified genetic risk factor is an allele from the MHC class II HLA-DRB1 gene, HLA-DRB1*15:01, which increases risk about threefold. The HLA-DRB1 gene is expressed in antigen-presenting cells, and its protein functions in presenting particular types of antigen to CD4 T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28453541/the-real-world-effectiveness-and-safety-of-fingolimod-in-relapsing-remitting-multiple-sclerosis-patients-an-observational-study
#20
Guillermo Izquierdo, Fátima Damas, Maria Dolores Páramo, Juan Luis Ruiz-Peña, Guillermo Navarro
Fingolimod approval was based mainly on two clinical trials, FREEDOMS and TRANSFORMS, which demonstrated the efficacy and safety of fingolimod in patients with multiple sclerosis (MS). We present an observational study that validates these trials findings in a real-world setting, whereby the effectiveness and safety of fingolimod was assessed in Seville's' (Spain) clinical practice. This retrospective study in MS patients assessed effectiveness (relapses, EDSS, gadolinium-enhancing T1 and new/enlarged T2-weighted lesions): total cohort (n = 249) and stratified according to prior treatment (glatiramer acetate/interferon beta-1 [immunomodulator], natalizumab, naïve), gender, basal EDSS score, basal Gd+ lesions, ARR prior to treatment, age at treatment initiation and number of prior treatments...
2017: PloS One
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