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https://www.readbyqxmd.com/read/29775134/csf-inflammatory-biomarkers-responsive-to-treatment-in-progressive-multiple-sclerosis-capture-residual-inflammation-associated-with-axonal-damage
#1
Jeppe Romme Christensen, Mika Komori, Marina Rode von Essen, Rikke Ratzer, Lars Börnsen, Bibi Bielekova, Finn Sellebjerg
BACKGROUND: Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. OBJECTIVE: To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. METHODS: CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS...
May 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29767705/gut-selective-integrin-targeted-therapies-for-inflammatory-bowel-disease
#2
Christopher A Lamb, Sharon O'Byrne, Mary E Keir, Eugene C Butcher
Integrins are cell surface receptors with bi-directional signaling capabilities that can bind to adhesion molecules in order to mediate homing of leukocytes to peripheral tissues. Gut-selective leukocyte homing is facilitated by interactions between α4β7 and its ligand MAdCAM-1, while retention of lymphocytes in mucosal tissues is mediated by αEβ7 binding to its ligand E-cadherin. Therapies targeting gut-selective trafficking have shown efficacy in inflammatory bowel disease (IBD), confirming the importance of leukocyte trafficking in disease pathobiology...
May 15, 2018: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29758075/effectiveness-and-safety-of-rituximab-in-multiple-sclerosis-an-observational-study-from-southern-switzerland
#3
Barbara Scotti, Giulio Disanto, Rosaria Sacco, Marilu' Guigli, Chiara Zecca, Claudio Gobbi
BACKGROUND: Despite positive results from phase II and observational studies, Rituximab (RTX) is not currently approved for multiple sclerosis (MS) treatment and can only be used off-label. OBJECTIVE: To characterize MS patients treated with RTX and investigate its effectiveness and safety in a clinical practice setting. METHODS: Observational analysis of data collected from MS patients at the Neurocenter of Southern Switzerland. Relapses, EDSS worsening, MRI lesion accrual and "evidence of disease activity" (EDA) status were described by Cox regression...
2018: PloS One
https://www.readbyqxmd.com/read/29754703/progression-of-a-series-of-patients-with-relapsing-remitting-multiple-sclerosis-treated-for-7-years-with-natalizumab-using-the-no-evidence-of-disease-activity-parameter
#4
A Pato Pato, E Costa Arpín, A Rodríguez Regal, I Rodríguez Constenla, I Cimas Hernando, I Muñoz Pousa, L Naya Ríos, J R Lorenzo González, M C Amigo Jorrín, J M Prieto González
INTRODUCTION: The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions. OBJECTIVE: To determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the "no evidence of disease activity" (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters...
May 10, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/29740202/anti-integrin-therapy-for-inflammatory-bowel-disease
#5
REVIEW
Sung Chul Park, Yoon Tae Jeen
In inflammatory bowel disease (IBD), tumor necrosis factor plays an important role in mediating inflammation, but several other pathways are also involved in eliciting an inflammatory response. One such pathway is the invasion of the intestinal mucosa by leukocytes. Leukocytes within the systemic circulation move to sites of inflammation, and blocking this pathway could be an important treatment strategy for IBD. Anti-integrin therapy blocks the action of integrin on the surface of circulating immune cells and endothelial cell adhesion molecules, thereby inhibiting the interactions between leukocytes and intestinal blood vessels...
May 7, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29731272/pediatric-multiple-sclerosis-and-fulminant-disease-course-features-and-approaches-to-treatment-a-case-report-and-review-of-the-literature
#6
REVIEW
Dániel Sandi, Edit Bereg, Tamás Biernacki, Erika Vörös, Péter Klivényi, Csaba Bereczki, László Vécsei, Krisztina Bencsik
Multiple sclerosis (MS) is the autoimmune, neurodegenerative disease of the central nervous system (CNS). Typically, it affects the young adult population, however, up to 10% of the cases, it can develop in childhood. Atypical manifestations, such as the tumefactive variant (tMS) or acute disseminated encephalomyelitis (ADEM), especially coupled with fulminant disease course, are even more rare and pose a considerable differential diagnostic and therapeutic challenge. Recently, the therapeutic strategy on the use of disease modifying therapies (DMTs) in MS has shifted to the direction of a more individualized approach, that takes the personal differences heavily into account, in particular regard to the activity and prognosis of the disease...
May 3, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29722639/efficacy-of-rituximab-in-refractory-rrms
#7
Pierre Durozard, Adil Maarouf, Clémence Boutiere, Aurelie Ruet, Bruno Brochet, Sandra Vukusic, Clarisse Carra-Dalliere, Pierre Labauge, Guillaume Mathey, Marc Debouverie, Caroline Papeix, Elisabeth Maillart, Catherine Lubetzki, Caroline Bensa, Olivier Gout, Claire Giannesini, Bruno Stankoff, Jonathan Ciron, David Brassat, Jean Pelletier, Audrey Rico Lamy, Bertrand Audoin
OBJECTIVE: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT). METHODS: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months...
May 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29709947/a-punctate-magnetic-resonance-imaging-pattern-in-a-patient-with-systemic-lupus-erythematosus-is-an-early-sign-of-progressive-multifocal-leukoencephalopathy-a-clinicopathological-study
#8
Junko Ishii, Yukiko Shishido-Hara, Michi Kawamoto, Satoru Fujiwara, Yukihiro Imai, Kazuo Nakamichi, Nobuo Kohara
A 37-year-old woman with systemic lupus erythematosus (SLE) presented with gait disturbance and cognitive dysfunction. Brain magnetic resonance imaging (MRI) revealed small, punctate, T2-/fluid-attenuated inversion recovery-hyperintense and T1-hypointense lesions without gadolinium enhancement, which is atypical for progressive multifocal leukoencephalopathy (PML). On a pathological examination of biopsied brain tissues, JC virus-infected cells were hardly detected via immunohistochemistry but were certainly detected via in situ hybridization, conclusively verifying the PML diagnosis...
April 27, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29708072/a-review-on-clinical-pharmacokinetics-pharmacodynamics-and-pharmacogenomics-of-natalizumab-a-humanized-anti-%C3%AE-4-integrin-monoclonal-antibody
#9
Li Hao, Shi Fang-Hong, Huang Shi-Ying, Zhang Shun-Guo, Chen Min-Ling
Natalizumab (Tysabri®, Biogen-Idec Inc., NAT), a humanized anti-α4 integrin monoclonal antibody, binds in both α4β1 (Very Late Antigen 4, VLA-4) and α4β7 (lymphocytes Peyer's patch adhesion molecule 1, LPAM-1) integrins, is approved for the treatment of Multiple sclerosis (MS) and Crohn's disease (CD). NAT has been well tolerated in pivotal trials. Progressive multifocal leukoencephalopathy (PML) is an uncommon but serious complications resulting from NAT treatment. It is not confirmed that higher NAT concentration increases the risk of PML...
April 27, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29695598/preapproval-and-postapproval-evidence-on-drugs-for-multiple-sclerosis
#10
REVIEW
Chiara Gerardi, Vittorio Bertele', Silvia Rossi, Silvio Garattini, Rita Banzi
OBJECTIVE: To review the evidence supporting the European Union marketing authorization of drugs for multiple sclerosis (MS) and assess how far postmarketing research addresses information gaps at the time of approval. METHODS: Through its database, we identified drugs approved by the European Medicines Agency and gathered data on pivotal trials from the European Public Assessment Reports and corresponding publications. We searched Medline, Embase, Cochrane Library, and trial registries for postmarketing randomized controlled trials testing the drugs identified in any form of the disease...
April 25, 2018: Neurology
https://www.readbyqxmd.com/read/29686116/practice-guideline-recommendations-summary-disease-modifying-therapies-for-adults-with-multiple-sclerosis-report-of-the-guideline-development-dissemination-and-implementation-subcommittee-of-the-american-academy-of-neurology
#11
Alexander Rae-Grant, Gregory S Day, Ruth Ann Marrie, Alejandro Rabinstein, Bruce A C Cree, Gary S Gronseth, Michael Haboubi, June Halper, Jonathan P Hosey, David E Jones, Robert Lisak, Daniel Pelletier, Sonja Potrebic, Cynthia Sitcov, Rick Sommers, Julie Stachowiak, Thomas S D Getchius, Shannon A Merillat, Tamara Pringsheim
OBJECTIVE: To develop recommendations for disease-modifying therapy (DMT) for multiple sclerosis (MS). METHODS: A multidisciplinary panel developed DMT recommendations, integrating findings from a systematic review; followed an Institute of Medicine-compliant process to ensure transparency and patient engagement; and developed modified Delphi consensus-based recommendations concerning starting, switching, and stopping DMTs pertinent to people with relapsing-remitting MS, secondary progressive MS, primary progressive MS, and clinically isolated syndromes of demyelination...
April 24, 2018: Neurology
https://www.readbyqxmd.com/read/29685294/epstein-barr-virus-associated-immune-reconstitution-inflammatory-syndrome-as-possible-cause-of-fulminant-multiple-sclerosis-relapse-after-natalizumab-interruption
#12
Barbara Serafini, Stephanie Zandee, Barbara Rosicarelli, Eleonora Scorsi, Caterina Veroni, Catherine Larochelle, Sandra D'Alfonso, Alexandre Prat, Francesca Aloisi
No abstract text is available yet for this article.
June 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29685071/comparative-analysis-of-natalizumab-versus-fingolimod-as-second-line-treatment-in-relapsing-remitting-multiple-sclerosis
#13
Johannes Lorscheider, Pascal Benkert, Carmen Lienert, Peter Hänni, Tobias Derfuss, Jens Kuhle, Ludwig Kappos, Özgür Yaldizli
BACKGROUND: No randomized controlled trials have compared the efficacy of fingolimod or natalizumab as second-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE: To compare clinical outcomes after escalation to fingolimod versus natalizumab in patients with clinically active RRMS. METHODS: Using the registry of the Swiss Federation for Common Tasks of Health Insurances, we identified patients with RRMS and ≥1 relapse in the year before switching from interferon beta or glatiramer acetate to fingolimod or natalizumab...
April 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29682547/jc-virus-dna-detection-is-associated-with-cd8-effector-accumulation-in-peripheral-blood-of-patients-with-multiple-sclerosis-under-natalizumab-treatment-independently-from-jc-virus-serostatus
#14
Maria A Zingaropoli, Marco Iannetta, Simona Pontecorvo, Elena Anzivino, Carla Prezioso, Donatella Maria Rodio, Manuela Morreale, Alessandra D'Abramo, Alessandra Oliva, Miriam Lichtner, Antonio Cortese, Marco Frontoni, Valeria Pietropaolo, Ada Francia, Claudio M Mastroianni, Vincenzo Vullo, Maria R Ciardi
Although natalizumab (anti- α 4 integrin) represents an effective therapy for relapsing remitting multiple sclerosis (RRMS), it is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), caused by the polyomavirus JC (JCV). The aim of this study was to explore natalizumab-induced phenotypic changes in peripheral blood T-lymphocytes and their relationship with JCV reactivation. Forty-four patients affected by RRMS were enrolled. Blood and urine samples were classified according to natalizumab infusion number: 0 ( N 0), 1-12 ( N 12), 13-24 ( N 24), 25-36 ( N 36), and over 36 ( N > 36) infusions...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29672587/functional-relevance-of-in-vivo-half-antibody-exchange-of-an-igg4-therapeutic-antibody-drug-conjugate
#15
Peter Herbener, Kurt Schönfeld, Martin König, Matthias Germer, Jude M Przyborski, Katrin Bernöster, Jörg Schüttrumpf
An increasing number of monoclonal antibodies and derivatives such as antibody-drug conjugates (ADC) are of the IgG1 and IgG4 isotype with distinct structural and functional properties. In cases where antibody-mediated cytotoxicity is not desired, IgG4 is often used, as its Fc region is relatively poor at inducing antibody-dependent cell-mediated or complement-dependent cytotoxicity. IgG4 ADCs with highly cytotoxic drugs against proliferating target cells but which lack or have diminished antibody effector functions against quiescent cells may have a favorable safety profile compared to IgG1...
2018: PloS One
https://www.readbyqxmd.com/read/29669908/progressive-multifocal-leukoencephalopathy-after-fingolimod-treatment
#16
Joseph R Berger, Bruce A Cree, Benjamin Greenberg, Bernhard Hemmer, Brian J Ward, Victor M Dong, Martin Merschhemke
OBJECTIVE: We describe the characteristics of the 15 patients with fingolimod-associated progressive multifocal leukoencephalopathy (PML) identified from the Novartis data safety base and provide risk estimates for the disorder. METHODS: The Novartis safety database was searched for PML cases with a data lock point of August 31, 2017. PML classification was based on previously published criteria. The risk and incidence were estimated using the 15 patients with confirmed PML and the overall population of patients treated with fingolimod...
April 18, 2018: Neurology
https://www.readbyqxmd.com/read/29668955/what-is-the-risk-of-progressive-multifocal-leukoencephalopathy-in-patients-with-ulcerative-colitis-or-crohn-s-disease-treated-with-vedolizumab
#17
Timothy Card, Jing Xu, Huifang Liang, Fatima Bhayat
Background: Progressive multifocal leukoencephalopathy is a serious condition linked to certain diseases and immunosuppressant therapies, including the α4 integrin antagonist natalizumab. No cases have been reported to date with vedolizumab, a selective antagonist of the α4β7 integrin expressed on gut-homing lymphocytes. This analysis aimed to describe the current and future expected occurrence of progressive multifocal leukoencephalopathy with vedolizumab use, were the risk the same as in other populations in which this disease has been studied...
April 13, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29663814/new-biological-agents-in-the-treatment-of-multiple-sclerosis
#18
M Buc
Multiple sclerosis (MS) is an inflammatory disease induced by autoimmune processes. Their understanding has resulted in an introduction of biological agents to its treatment. Interferon beta and glatiramer acetate have been in clinical practice for more than 20 years. Nowadays, novel biologics, which target molecules involved in immunopathological processes more specifically have entered the scene. They are represented by monoclonal antibodies binding to molecules VLA4 (natalizumab), CD20 (ocrelizumab), CD52 (alemtuzumab) or alpha subunit of IL-2 receptor (daclizumab) or by small molecules such as those modulating the receptors involved in regulation of lymphocyte migration (fingolimod, ozanimod) or in induction of lymphopenia by apoptosis (dimethyl fumarate, cladribine)...
2018: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29659729/t-helper-17-1-cells-associate-with-multiple-sclerosis-disease-activity-perspectives-for-early-intervention
#19
Jamie van Langelaar, Roos M van der Vuurst de Vries, Malou Janssen, Annet F Wierenga-Wolf, Isis M Spilt, Theodora A Siepman, Wendy Dankers, Georges M G M Verjans, Helga E de Vries, Erik Lubberts, Rogier Q Hintzen, Marvin M van Luijn
Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients...
April 5, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29656742/pathogenesis-of-progressive-multifocal-leukoencephalopathy-and-risks-associated-with-treatments-for-multiple-sclerosis-a-decade-of-lessons-learned
#20
REVIEW
Eugene O Major, Tarek A Yousry, David B Clifford
Progressive multifocal leukoencephalopathy (PML) is a rare, devastating demyelinating disease of the CNS caused by the JC virus (JCV) that occurs in patients with compromised immune systems. Detection of PML in systemically immunocompetent patients with multiple sclerosis treated with natalizumab points to a role for this drug in the pathophysiology of PML. Emerging knowledge of the cellular and molecular biology of JCV infection and the pathogenesis of PML-including interplay of this common virus with the human immune system and features of natalizumab that might contribute to PML pathogenesis-provides new opportunities to monitor viral status and predict risk of JCV-associated disease...
May 2018: Lancet Neurology
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