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Konstantinos H Katsanos, Konstantinos Papamichael, Joseph D Feuerstein, Dimitrios K Christodoulou, Adam S Cheifetz
The pharmacological management of inflammatory bowel disease (IBD) over the last two decades has transitioned from reliance on aminosalycilates, corticosteroids and immunomodulators to earlier treatment with anti-tumor necrosis factor (anti-TNF) therapy. Nevertheless, 20-30% of patients discontinue anti-TNF therapy for primary non-response and another 30-40% for losing response within one year of treatment. These undesirable therapeutic outcomes can be attributed to pharmacokinetic (anti-drug antibodies and/or low drug concentrations) or pharmacodynamic issues characterized by a non-TNF driven inflammation...
March 12, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Gilles Edan
No abstract text is available yet for this article.
March 12, 2018: Lancet Neurology
Raju Kapoor, Pei-Ran Ho, Nolan Campbell, Ih Chang, Aaron Deykin, Fiona Forrestal, Nisha Lucas, Bei Yu, Douglas L Arnold, Mark S Freedman, Myla D Goldman, Hans-Peter Hartung, Eva Kubala Havrdová, Douglas Jeffery, Aaron Miller, Finn Sellebjerg, Diego Cadavid, Dan Mikol, Deborah Steiner
BACKGROUND: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. METHODS: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2)...
March 12, 2018: Lancet Neurology
Shinji Aoyama, Masahiro Mori, Akiyuki Uzawa, Tomohiko Uchida, Hiroki Masuda, Ryohei Ohtani, Satoshi Kuwabara
BACKGROUND: The risk of developing progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis (MS) patients is related to serum anti-JCV antibody (JCVAb) index. However, the correlation of JCVAb index with other disease-modifying treatments (DMTs) is not well understood. OBJECTIVE: In this study, we investigated the JCVAb seropositivity rate/JCVAb indexes and its correlation with clinical profiles in Japanese MS patients, and the relationship between JCVAb indexes and DMTs...
March 12, 2018: Journal of Neurology
Martijn T Wijburg, Iris Kleerekooper, Birgit I Lissenberg-Witte, Marlieke de Vos, Clemens Warnke, Bernard M J Uitdehaag, Frederik Barkhof, Joep Killestein, Mike P Wattjes
Importance: The JC virus (JCV) was named after the first patient to be described with progressive multifocal leukoencephalopathy (PML), John Cunningham. Detection of JC virus DNA in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), and of specific lesions by brain magnetic resonance imaging (MRI), are both considered essential for the diagnosis of natalizumab-associated PML (NTZ-PML) in patients with multiple sclerosis. However, strict pharmacovigilance by MRI can result in detection of patients with small lesions and undetectable JCV DNA in CSF...
March 12, 2018: JAMA Neurology
Stanley L Cohan, Harold Moses, Jonathan Calkwood, Carlo Tornatore, Chris LaGanke, Kyle E Smoot, Venkata Meka, Macaulay Okwuokenye, Christophe Hotermans, Jason P Mendoza, Monica K Mann, Leslie A Meltzer
BACKGROUND: Delayed-release dimethyl fumarate (DMF) may be a therapeutic option for patients with relapsing-remitting multiple sclerosis (RRMS) who are treated with natalizumab and require a change in therapy. However, there is limited information regarding predictors of favorable treatment outcomes in patients switching from natalizumab to DMF. Clinical practices and sequencing protocols vary. Herein, we present the clinical results, including annualized relapse rate (ARR) and risk of relapse, of a phase 4 retrospective observational study of patients with RRMS who switched from natalizumab to DMF in a community practice setting (STRATEGY)...
February 26, 2018: Multiple Sclerosis and related Disorders
Raed Alroughani, Alexey Boyko
BACKGROUND: Pediatric-onset multiple sclerosis (POMS) prevalence and incidence rates are increasing globally. No disease-modifying therapy are approved for MS pediatric population. Hence, we aim to review the literature on POMS to guide treating physicians on the current understanding of diagnosis and management of pediatric MS. METHODS: The authors performed a literature search and reviewed the current understanding on risk factors and disease parameters in order to discuss the challenges in assessing and implementing diagnosis and therapy in clinical practice...
March 9, 2018: BMC Neurology
Sherif M Hamdy, Maged Abdel-Naseer, Nevin M Shalaby, Alaa Elmazny, Marian Girgis, Mona A Nada, Amr Hassan, Husam S Mourad, Mohamed I Hegazy, Ahmed Abdelalim, Nirmeen A Kishk, Noha T Abokrysha, Shaimaa A Genedy, Ehab A Essawy, Hatem S Shehata
Introduction: Although the frequency of pediatric-onset multiple sclerosis (POMS) has increased in recent decades, it is still highly uncommon, which creates a need for the involvement of more registries from various clinical centers. Objective: To characterize the demographic, clinical, and paraclinical features of Egyptian patients with POMS. Patients and methods: A retrospective chart review study was undertaken on 237 Egyptian patients with demyelinating events which started before the age of 18 years who attended one of five tertiary referral centers in Cairo, Egypt...
2018: Neuropsychiatric Disease and Treatment
Afsaneh Shirani, Olaf Stüve
Probably no other disease-modifying drug for multiple sclerosis has a more fascinating story than natalizumab from both the bench to bedside perspective and the postmarketing experience standpoint. Natalizumab is a monoclonal antibody that inhibits the trafficking of lymphocytes from the blood into the central nervous system by blocking the adhesion molecule α4-integrin. Natalizumab was approved as a disease-modifying drug for relapsing remitting multiple sclerosis only 12 years after the discovery of its target molecule-a time line that is rather fast for drug development...
March 2, 2018: Cold Spring Harbor Perspectives in Medicine
Li Wang, Chun-Hui Qi, Ren Zhong, Chao Yuan, Qiu-Yue Zhong
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease, in which the insulating covers of nerve cells in the brain and spinal cord are demyelinated. This study was conducted to compare the efficacy of alemtuzumab and natalizumab in the treatment of different stages of MS patients. METHODS: A total of 585 patients diagnosed with MS and hospitalized were included and analyzed after which they were divided into the primary progressive MS A and B groups, the relapsing-remitting MS (RRMS) C and D groups, and the secondary progressive MS E and F groups...
February 2018: Medicine (Baltimore)
Elizabeth A Mills, Yang Mao-Draayer
The increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes within the central nervous system (CNS) leading to increased anti-inflammatory subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating disease of the CNS, but it is caused by the JC virus...
2018: Frontiers in Immunology
M Saraste, S Atula, K Hedman, S Hurme, A Jalkanen, M Sneck, H-M Surcel, A H Maghzi, L Airas
BACKGROUND: Pregnancy induces an immunosuppressive state in the mother to ensure immunological acceptance of the foetus. Impairment of cell-mediated immune responses may render the mother susceptible to intracellular pathogens. It is not presently known whether pregnancy alters the immunosurveillance for John Cunningham virus (JCV), an opportunistic pathogen associated with natalizumab treatment for multiple sclerosis (MS). OBJECTIVE: To evaluate whether the humoral immune response to JCV is altered during pregnancy among MS patients and healthy controls to get insight to potential pregnancy-induced alterations related to immune response to JCV during pregnancy...
February 9, 2018: Multiple Sclerosis and related Disorders
Ségolène Roemer, Alexandre Bissig, Alda Rocca, Renaud Du Pasquier, Yan Guex-Crosier
No abstract text is available yet for this article.
February 16, 2018: Klinische Monatsblätter Für Augenheilkunde
Pietro Iaffaldano, Domenico Ribatti, Maria Trojano
Angiogenesis has been implicated in the pathobiology of multiple sclerosis (MS). Osteopontin exerts a pro-angiogenetic effect and is increased in body fluid of MS patients. To evaluate the effect of 1 year natalizumab treatment on serum pro-angiogenic activity and on plasma osteopontin levels in relapsing (RR) MS patients. Ten RRMS patients scheduled for natalizumab treatment were enrolled and evaluated at baseline and after 1-year natalizumab treatment. Pro-angiogenic activity was assessed by a chick embryo chorioallantoic membrane assay (CAM), osteopontin levels were evaluated by an enzyme-linked immunosorbent assay...
February 13, 2018: Neurological Sciences
Emilio Portaccio, Pietro Annovazzi, Angelo Ghezzi, Mauro Zaffaroni, Lucia Moiola, Vittorio Martinelli, Roberta Lanzillo, Vincenzo Brescia Morra, Francesca Rinaldi, Paolo Gallo, Carla Tortorella, Damiano Paolicelli, Carlo Pozzilli, Laura De Giglio, Paola Cavalla, Eleonora Cocco, Maria Giovanna Marrosu, Francesco Patti, Claudio Solaro, Paolo Bellantonio, Antonio Uccelli, Alice Laroni, Luisa Pastò, Marta Giannini, Maria Trojano, Giancarlo Comi, Maria Pia Amato
OBJECTIVE: To assess fetal risk after pregnancy exposure to natalizumab in women with multiple sclerosis (MS), with a specific focus on spontaneous abortion (SA) and congenital anomalies (CA). METHODS: Data of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents...
March 6, 2018: Neurology
Emilio Portaccio, Lucia Moiola, Vittorio Martinelli, Pietro Annovazzi, Angelo Ghezzi, Mauro Zaffaroni, Roberta Lanzillo, Vincenzo Brescia Morra, Francesca Rinaldi, Paolo Gallo, Carla Tortorella, Damiano Paolicelli, Carlo Pozzilli, Laura De Giglio, Paola Cavalla, Eleonora Cocco, Maria Giovanna Marrosu, Claudio Solaro, Antonio Uccelli, Alice Laroni, Luisa Pastò, Marta Giannini, Maria Trojano, Giancarlo Comi, Maria Pia Amato
OBJECTIVE: To assess the risk of disease reactivation during pregnancy after natalizumab suspension in women with multiple sclerosis (MS). METHODS: Data of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents through a 2-factor repeated measures analysis...
February 7, 2018: Neurology
Ruth Ann Marrie
No abstract text is available yet for this article.
February 7, 2018: Neurology
F Esposito, L Ferrè, F Clarelli, M A Rocca, G Sferruzza, L Storelli, M Radaelli, F Sangalli, L Moiola, B Colombo, F Martinelli Boneschi, G Comi, M Filippi, V Martinelli
BACKGROUND: Treatment choice in multiple sclerosis (MS) is crucial for optimizing risk-benefit profile. OBJECTIVE: To assess fingolimod (FTY) effectiveness and identify baseline features associated to disease activity in a large Italian cohort of Relapsing-Remitting (RR) MS patients. METHODS: Three-hundred sixty-seven RRMS patients starting FTY treatment at San Raffaele Hospital (Milan-Italy) underwent clinical and MRI evaluations for 2 years...
February 12, 2018: Journal of Neurology
Raed Alroughani, Maryam S Alowayesh, Samar F Ahmed, Raed Behbehani, Jasem Al-Hashel
OBJECTIVE: To determine the rate of relapse occurrence during pregnancy and postpartum. METHODS: In a cross-sectional study using the national multiple sclerosis (MS) registry, pregnant women with relapsing MS were identified. Data on demographics, clinical characteristics, and disease-modifying therapies (DMTs), including washout periods, were collected. Timings and durations of relapses were extracted. A multivariate logistic regression was used to assess the relationship between relapses and prior use of different DMTs...
February 2, 2018: Neurology
Gil Redelman-Sidi, Olivier Michielin, Carlos Cervera, Camillo Ribi, José María Aguado, Mario Fernández-Ruiz, Oriol Manuel
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3-targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 7, 2018: Clinical Microbiology and Infection
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