Publications by authors named "Jiwon Oh"

112 Publications

Efficacy and Safety of Teriflunomide in Multiple Sclerosis across Age Groups: Analysis from Pooled Pivotal and Real-world Studies.

J Cent Nerv Syst Dis 2021 29;13:11795735211028781. Epub 2021 Jul 29.

Universite de Lille, Inserm U1172, CHU Lille, FHU Precise, Lille, France.

Background: Evidence suggests that efficacy and safety of disease-modifying treatments for multiple sclerosis may differ with age. We evaluate efficacy and safety of teriflunomide across age subgroups of patients from pooled clinical trials and real-world studies.

Methods: Post hoc analyses of patients who received teriflunomide 14 mg in the pooled phase II and III TEMSO, TOWER, TENERE, and TOPIC core and extension studies (n 1978), and the real-world Teri-PRO (n 928) and TAURUS-MS I (n 1126) studies were conducted. Data were stratified by age at study entry: ⩽25, >25 to ⩽35, >35 to ⩽45, and >45 years. In Teri-PRO and TAURUS-MS I, an additional group, >55 years, was assessed.

Results: In the pooled core studies, teriflunomide reduced annualized relapse rate (ARR) versus placebo across all ages. Unadjusted ARRs remained low across age groups in pooled extensions (0.18-0.30), Teri-PRO (0.10-0.35), and TAURUS-MS I (0.14-0.35). Baseline Expanded Disability Status Scale scores were higher with age, but stable through core and extension studies (mean increases over 7 years: ⩽25 years, +0.59; >25 to ⩽35 years, +0.46; >35 to ⩽45 years, +0.35; >45 years, +0.81). Across age groups, adverse event (AE) incidences were 78.4% to 90.7% in pooled core and extension studies and Teri-PRO, and 29.2% to 37.7% in TAURUS-MS I; serious AE incidences were ⩽21.3% in all studies. In pooled phase III and Teri-PRO studies, lymphocyte count decreases over 1 year after initiating teriflunomide, and proportions of patients developing lymphopenia, were small across age groups.

Conclusions: Teriflunomide efficacy was demonstrated regardless of age. Safety was generally consistent across age groups.
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http://dx.doi.org/10.1177/11795735211028781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330455PMC
July 2021

Corrigendum to "Effects of a health-belief-model-based osteoporosis- and fall-prevention program on women at early old age" [Applied Nursing Research 59 (2021) 151430].

Authors:
Sukhee Ahn Jiwon Oh

Appl Nurs Res 2021 Aug 6:151452. Epub 2021 Aug 6.

Chungnam National University, College of Nursing, South Korea. Electronic address:

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http://dx.doi.org/10.1016/j.apnr.2021.151452DOI Listing
August 2021

Treatment-emergent adverse events occurring early in the treatment course of cladribine tablets in two phase 3 trials in multiple sclerosis.

Mult Scler J Exp Transl Clin 2021 Jul-Sep;7(3):20552173211024298. Epub 2021 Jul 13.

Comprehensive Multiple Sclerosis Center, Jefferson University, Philadelphia, PA, USA.

Background: Treatment-emergent adverse events (TEAEs) that occur close to treatment initiation may negatively affect overall tolerability and adherence. It is important to develop a clear understanding of potential early TEAEs after initiating treatment with cladribine tablets.

Objective: To identify TEAEs that begin early in the course of treatment in patients enrolled in CLARITY and ORACLE-MS studies.

Methods: This analysis of CLARITY and ORACLE-MS safety populations assessed the incidence of TEAEs, serious TEAEs, drug-related TEAEs, and TEAEs leading to discontinuation in patients receiving cladribine tablets or placebo within 2, 6, and 12 weeks after treatment initiation.

Results: By Week 12, 61.3% of patients treated with cladribine tablets 3.5 mg/kg and 55.2% treated with placebo experienced a TEAE. More patients receiving cladribine tablets versus placebo experienced a drug-related TEAE by Week 12 (34.7% vs. 23.2%). The most common TEAEs reported with cladribine tablets were: headache (7.2%), lymphopenia (6.8%), and nausea (6.0%). Patients receiving cladribine tablets and placebo reported similar proportions of serious TEAEs (2.2% vs. 1.7%) and TEAEs leading to treatment discontinuation (1.6% vs. 1.4%).

Conclusion: Cladribine tablets were well tolerated during the first 12 weeks as evidenced by a low incidence of TEAEs leading to treatment discontinuation.
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http://dx.doi.org/10.1177/20552173211024298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283088PMC
July 2021

Development and Validation of the Stroke Symptom Cluster Scale Among Korean Stroke Survivors: Mixed-Methods Design.

Rehabil Nurs 2021 Jul 20. Epub 2021 Jul 20.

College of Nursing, Chungnam National University, Daejeon, South Korea College of Nursing, Woosuk University, Wanju-gun, South Korea College of Medicine, Chungnam National University, Daejeon, South Korea.

Purpose: This study aimed to develop and validate the Stroke Symptom Cluster Scale for Korean Adults (SSCS-K) for stroke survivors.

Design: An exploratory sequential study with a mixed-methods design was performed.

Methods: In the development stage, a qualitative study with in-depth interviews was conducted with 27 stroke patients. The validation stage involved analyzing the psychometric properties from 288 stroke patients.

Findings: The SSCS-K comprising 65 items in six dimensions (mobility, cognition, sensory, mood, communication, and swallowing difficulty) demonstrated acceptable internal consistency (Cronbach's α = .92-.94). Confirmatory factor analyses with a six-factor solution showed that it explained 62% of the variance in stroke symptoms. The concurrent validity was confirmed with the Stroke-Specific Quality of Life Scale (r = .38-.83, p < .001).

Conclusion: The SSCS-K has strong psychometric properties as a measure to assess clustered symptoms in stroke survivors during their long-term rehabilitation.

Clinical Relevance: Rehabilitation nurses may consider the SSCS-K as a useful tool for assessing symptoms of stroke survivors.
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http://dx.doi.org/10.1097/RNJ.0000000000000339DOI Listing
July 2021

The potential of serum neurofilament as biomarker for multiple sclerosis.

Brain 2021 Jun 28. Epub 2021 Jun 28.

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Multiple sclerosis is a highly heterogeneous disease and the detection of neuroaxonal damage as well as its quantification is a critical step for patients. Blood-based neurofilament light chain (sNfL) is currently under close investigation as an easily accessible biomarker of prognosis and treatment response for multiple sclerosis patients. There is abundant evidence that sNfL levels reflect ongoing inflammatory-driven neuroaxonal damage (e.g. relapses or MRI disease activity) and that sNfL levels predict disease activity over the next few years. In contrast, the association of sNfL with long-term clinical outcomes or its ability to reflect slow, diffuse neurodegenerative damage in multiple sclerosis is less clear. However, early results from real-world cohorts and clinical trials using sNfL as a marker of treatment response in multiple sclerosis are encouraging. Importantly, clinical algorithms should now be developed that incorporate the routine use of sNfL to guide individualized clinical decision-making in people with multiple sclerosis, together with additional fluid biomarkers and clinical and MRI measures. Here, we propose specific clinical scenarios where implementing sNfL measures may be of utility, including, among others: initial diagnosis, first treatment choice, surveillance of subclinical disease activity and guidance of therapy selection.
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http://dx.doi.org/10.1093/brain/awab241DOI Listing
June 2021

Update on the management of multiple sclerosis during the COVID-19 pandemic and post pandemic: An international consensus statement.

J Neuroimmunol 2021 08 7;357:577627. Epub 2021 Jun 7.

Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Department of Neurology, Royal London Hospital, Barts Health NHS Trust, London, UK. Electronic address:

In this consensus statement, we provide updated recommendations on multiple sclerosis (MS) management during the COVID-19 crisis and the post-pandemic period applicable to neurology services around the world. Statements/recommendations were generated based on available literature and the experience of 13 MS expert panelists using a modified Delphi approach online. The statements/recommendations give advice regarding implementation of telemedicine; use of disease-modifying therapies and management of MS relapses; management of people with MS at highest risk from COVID-19; management of radiological monitoring; use of remote pharmacovigilance; impact on MS research; implications for lowest income settings, and other key issues.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183006PMC
August 2021

2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis.

Lancet Neurol 2021 08 14;20(8):653-670. Epub 2021 Jun 14.

Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address:

The 2015 Magnetic Resonance Imaging in Multiple Sclerosis and 2016 Consortium of Multiple Sclerosis Centres guidelines on the use of MRI in diagnosis and monitoring of multiple sclerosis made an important step towards appropriate use of MRI in routine clinical practice. Since their promulgation, there have been substantial relevant advances in knowledge, including the 2017 revisions of the McDonald diagnostic criteria, renewed safety concerns regarding intravenous gadolinium-based contrast agents, and the value of spinal cord MRI for diagnostic, prognostic, and monitoring purposes. These developments suggest a changing role of MRI for the management of patients with multiple sclerosis. This 2021 revision of the previous guidelines on MRI use for patients with multiple sclerosis merges recommendations from the Magnetic Resonance Imaging in Multiple Sclerosis study group, Consortium of Multiple Sclerosis Centres, and North American Imaging in Multiple Sclerosis Cooperative, and translates research findings into clinical practice to improve the use of MRI for diagnosis, prognosis, and monitoring of individuals with multiple sclerosis. We recommend changes in MRI acquisition protocols, such as emphasising the value of three dimensional-fluid-attenuated inversion recovery as the core brain pulse sequence to improve diagnostic accuracy and ability to identify new lesions to monitor treatment effectiveness, and we provide recommendations for the judicious use of gadolinium-based contrast agents for specific clinical purposes. Additionally, we extend the recommendations to the use of MRI in patients with multiple sclerosis in childhood, during pregnancy, and in the post-partum period. Finally, we discuss promising MRI approaches that might deserve introduction into clinical practice in the near future.
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http://dx.doi.org/10.1016/S1474-4422(21)00095-8DOI Listing
August 2021

Effects of a Tai Chi-Based Stroke Rehabilitation Program on Symptom Clusters, Physical and Cognitive Functions, and Quality of Life: A Randomized Feasibility Study.

Int J Environ Res Public Health 2021 05 20;18(10). Epub 2021 May 20.

College of Medicine, Chungnam National University, Daejeon 35015, Korea.

Stroke survivors suffer from disease-associated symptoms. Tai Chi can be a beneficial approach to provide an adapted form of intervention to manage their symptoms. The study aimed to determine the effects of a Tai Chi-based stroke rehabilitation program on symptom clusters, physical and cognitive functions, and stroke-specific quality of life among stroke survivors in Korea. Thirty-four stroke survivors were randomly assigned to receive either the Tai Chi-based program or the stroke-symptom management program. The feasibility of the program and its effects on the outcomes were assessed at baseline, 3 months, and 6 months. Repeated measures ANOVA showed that most symptoms improved in both groups during the 6-month period, but swallowing-related symptoms improved significantly in the Tai Chi group. Based on the interaction effect, Tai Chi was more effective on flexor muscle strength, ambulation, and activities of daily living and cognitive function over 6 months than their counterparts. Among SS-QOL dimensions, the Tai Chi group showed significant improvements in the thinking and self-care dimensions. The Tai Chi-based stroke rehabilitation program was feasible and safely applicable to stroke survivors in the community settings. This program could improve symptoms, physical and cognitive function, leading to improvements in the self-care dimension of the SS-QOL among stroke survivors.
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http://dx.doi.org/10.3390/ijerph18105453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160714PMC
May 2021

A window into the future? MRI for evaluation of neuromyelitis optica spectrum disorder throughout the disease course.

Ther Adv Neurol Disord 2021 9;14:17562864211014389. Epub 2021 May 9.

St. Michael's Hospital, 30 Bond Street, Shuter 3-018, Toronto, ON, M5B 1W8, Canada.

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, inflammatory disease of the central nervous system marked by relapses often associated with poor recovery and long-term disability. Magnetic resonance imaging (MRI) is recognized as an important tool for timely diagnosis of NMOSD as, in combination with serologic testing, it aids in distinguishing NMOSD from possible mimics. Although the role of MRI for disease monitoring after diagnosis is not as well established, MRI may provide important prognostic information and help differentiate between relapses and pseudorelapses. Increasing evidence of subclinical disease activity and the emergence of newly approved, highly effective immunotherapies for NMOSD adjure us to re-evaluate MRI as a tool to guide optimal treatment selection and escalation throughout the disease course. In this article we review the role of MRI in NMOSD diagnosis, prognostication, disease monitoring, and treatment selection.
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http://dx.doi.org/10.1177/17562864211014389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111516PMC
May 2021

Ozanimod for the treatment of relapsing forms of multiple sclerosis.

Neurodegener Dis Manag 2021 06 20;11(3):207-220. Epub 2021 May 20.

Department of Medicine, Division of Neurology, St. Michael's Hospital University of Toronto, Toronto, Canada.

Multiple sclerosis (MS) is an inflammatory disease that causes chronic neurological disability in young adults. Modulation of sphingosine 1-phosphate (S1P) receptors, a group of receptors that, among other things, regulate egression of lymphocytes from lymph nodes, has proven to be effective in treating relapsing MS. Fingolimod, the first oral S1P receptor modulator, has demonstrated potent efficacy and tolerability, but can cause undesirable side effects due to its interaction with a wide range of S1P receptor subtypes. This review will focus on ozanimod, a more selective S1P receptor modulator, which has recently received approval for relapsing MS. We summarize ozanimod's mechanism of action, and efficacy and safety from clinical trials that demonstrate its utility as another treatment option for relapsing MS.
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http://dx.doi.org/10.2217/nmt-2021-0005DOI Listing
June 2021

Videoconferencing and Multiple Sclerosis Management: Stopgap or Stay Tuned?

Can J Neurol Sci 2021 May 17:1-4. Epub 2021 May 17.

University of British Columbia, Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1017/cjn.2021.113DOI Listing
May 2021

Effects of a health-belief-model-based osteoporosis- and fall-prevention program on women at early old age.

Authors:
Sukhee Ahn Jiwon Oh

Appl Nurs Res 2021 06 6;59:151430. Epub 2021 Apr 6.

Chungnam National University, College of Nursing, 266 Munhwa-ro, Jung-gu, Daejeon 35015, South Korea. Electronic address:

Background: Elderly women are at high risk of osteoporosis and falls. Lifestyle modifications and regular check-ups are strongly recommended to promote their bone health. However, elderly women tend to perform low preventive behaviors due to physiological changes associated with aging. Education facilitating healthy behaviors is essential for older women. Therefore, the purpose of this study was to determine whether a Health Belief Model (HBM)-based osteoporosis- and fall-prevention program could improve osteoporosis- and fall-prevention knowledge, self-efficacy, and health behaviors among women aged 65 to 74 years.

Methods: This study included an untreated control group with a pretest-posttest design. Women (n = 47) in the intervention group received four sessions of an HBM-based program within a 2-month period. Participants (n = 47) in the control group attended usual education sessions.

Results: Women in the intervention group exhibited greater knowledge in exercise and diet for osteoporosis-prevention (t = 5.473, p < 0.001; t = 6.895, p < 0.001, respectively), fall-prevention knowledge (t = 2.354, p = 0.021), self-efficacy in exercise for osteoporosis-prevention (t = 2.736, p = 0.008), osteoporosis-prevention behavior of exercise, diet, and routine follow-ups (t = 3.019, p = 0.003; t = 2.705, p = 0.008; t = 2.368, p = 0.020, respectively), and fall-prevention behavior (t = 3.879, p < 0.001).

Conclusion: HBM-based osteoporosis- and fall-prevention program exhibited outstanding effectiveness in promoting osteoporosis and fall prevention among women at early old age. Further studies with more rigorous designs are needed to provide further evidence that supports this finding.
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http://dx.doi.org/10.1016/j.apnr.2021.151430DOI Listing
June 2021

Vitamin D as disease-modifying therapy for multiple sclerosis?

Expert Rev Clin Immunol 2021 Jul 15;17(7):691-693. Epub 2021 Apr 15.

Division of Neurology, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1080/1744666X.2021.1915772DOI Listing
July 2021

Inhibition of NUPR1-Karyopherin β1 Binding Increases Anticancer Drug Sensitivity.

Int J Mol Sci 2021 Mar 10;22(6). Epub 2021 Mar 10.

Center for Metareceptome Research, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak, Seoul 06974, Korea.

Background: Nuclear protein-1 (NUPR1, also known as p8/Com-1) is a transcription factor involved in the regulation of cellular stress responses, including serum starvation and drug stimulation.

Methods: We investigated the mechanism of NUPR1 nuclear translocation involving karyopherin β1 (KPNB1), using a single-molecule binding assay and confocal microscopy. The cellular effects associated with NUPR1-KPNB1 inhibition were investigated by gene expression profiling and cell cycle analysis.

Results: The single-molecule binding assay revealed that KPNB1 bound to NUPR1 with a binding affinity of 0.75 nM and that this binding was blocked by the aminothiazole ATZ-502. Following doxorubicin-only treatment, NUPR1 was translocated to the nucleus in more than 90% and NUPR1 translocation was blocked by the ATZ-502 combination treatment in MDA-MB-231 with no change in NUPR1 expression, providing strong evidence that NUPR1 nuclear translocation was directly inhibited by the ATZ-502 treatment. Inhibition of KPNB1 and NUPR1 binding was associated with a synergistic anticancer effect (up to 19.6-fold) in various cancer cell lines. NUPR1-related genes were also downregulated following the doxorubicin-ATZ-502 combination treatment.

Conclusion: Our current findings clearly demonstrate that NUPR1 translocation into the nucleus requires karyopherin β1 binding. Inhibition of the KPNB1 and NUPR1 interaction may constitute a new cancer therapeutic approach that can increase the drug efficacy while reducing the side effects.
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http://dx.doi.org/10.3390/ijms22062794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000408PMC
March 2021

Manipulation of the Nanoscale Presentation of Integrin Ligand Produces Cancer Cells with Enhanced Stemness and Robust Tumorigenicity.

Nano Lett 2021 04 25;21(7):3225-3236. Epub 2021 Mar 25.

Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, 999077, China.

Developing strategies for efficient expansion of cancer stem-like cells (CSCs) will help investigate the mechanism underlying tumorigenesis and cancer recurrence. Herein, we report a dynamic culture substrate tethered with integrin ligand-bearing magnetic nanoparticles via a flexible polymeric linker to enable magnetic manipulation of the nanoscale ligand tether mobility. The cancer cells cultured on the substrate with high ligand tether mobility develop into large semispherical colonies with CSCs features, which can be abrogated by magnetically restricting the ligand tether mobility. Mechanistically, the substrate with high ligand tether mobility suppresses integrin-mediated mechanotransduction and histone-related methylation, thereby enhancing cancer cell stemness. The culture-derived high-stemness cells can generate tumors both locally and at the distant lung and uterus much more efficiently than the low-stemness cells. We believe that this magnetic nanoplatform provides a promising strategy for investigating the dynamic interaction between CSCs and the microenvironment and establishing a cost-effective tumor spheroid model.
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http://dx.doi.org/10.1021/acs.nanolett.1c00501DOI Listing
April 2021

Deep grey matter injury in multiple sclerosis: a NAIMS consensus statement.

Brain 2021 08;144(7):1974-1984

Department of Neurology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.

Although multiple sclerosis has traditionally been considered a white matter disease, extensive research documents the presence and importance of grey matter injury including cortical and deep regions. The deep grey matter exhibits a broad range of pathology and is uniquely suited to study the mechanisms and clinical relevance of tissue injury in multiple sclerosis using magnetic resonance techniques. Deep grey matter injury has been associated with clinical and cognitive disability. Recently, MRI characterization of deep grey matter properties, such as thalamic volume, have been tested as potential clinical trial end points associated with neurodegenerative aspects of multiple sclerosis. Given this emerging area of interest and its potential clinical trial relevance, the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative held a workshop and reached consensus on imaging topics related to deep grey matter. Herein, we review current knowledge regarding deep grey matter injury in multiple sclerosis from an imaging perspective, including insights from histopathology, image acquisition and post-processing for deep grey matter. We discuss the clinical relevance of deep grey matter injury and specific regions of interest within the deep grey matter. We highlight unanswered questions and propose future directions, with the aim of focusing research priorities towards better methods, analysis, and interpretation of results.
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http://dx.doi.org/10.1093/brain/awab132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370433PMC
August 2021

Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS.

Mult Scler 2021 Mar 23:13524585211002097. Epub 2021 Mar 23.

Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada/Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.

Objective: The central vein sign (CVS) and "paramagnetic rim lesions" (PRL) are emerging imaging biomarkers in multiple sclerosis (MS) reflecting perivenular demyelination and chronic, smoldering inflammation. The objective of this study was to assess relationships between cognitive impairment (CI) and the CVS and PRL in radiologically isolated syndrome (RIS).

Methods: Twenty-seven adults with RIS underwent 3.0 T MRI of the brain and cervical spinal cord (SC) and cognitive assessment using the minimal assessment of cognitive function in MS battery. The CVS and PRL were assessed in white-matter lesions (WMLs) on T2*-weighted segmented echo-planar magnitude and phase images. Multivariable linear regression evaluated relationships between CI and MRI measures.

Results: Global CI was present in 9 (33%) participants with processing speed and visual memory most frequently affected. Most participants (93%) had ⩾ 40% CVS + WML (a threshold distinguishing MS from other WM disorders); 63% demonstrated PRL. Linear regression revealed that CVS + WML predicted performance on verbal memory( =-0.024,  = 0.03) while PRL predicted performance on verbal memory ( = -0.040,  = 0.04) and processing speed ( = -0.039,  = 0.03).

Conclusions: CI is common in RIS and is associated with markers of perivenular demyelination and chronic inflammation in WML, such as CVS + WML and PRL. A prospective follow-up of this cohort will ascertain the importance of CI, CVS, and PRL as risk factors for conversion from RIS to MS.
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http://dx.doi.org/10.1177/13524585211002097DOI Listing
March 2021

Challenges in multiple sclerosis care: Results from an international mixed-methods study.

Mult Scler Relat Disord 2021 May 23;50:102854. Epub 2021 Feb 23.

AXDEV Group Inc., Brossard, Canada.

Background: Disease-modifying treatment (DMT) selection for people with multiple sclerosis (MS) is challenging. Neurologists and advanced practice nurses (APNs) in MS care may be facing knowledge and confidence gaps when screening patients to initiate or switch between DMTs, assessing the safety of new DMTs and monitoring for adverse events. Healthcare providers are required to demonstrate enhanced patient communication skills, to share treatment decisions and assess treatment adherence. To better inform educational interventions, there is a need to better understand these challenges and uncover their causalities. We undertook an international study across seven countries to identify challenges for neurologists and APNs that may impact DMT choices and optimum care for people with MS (pwMS).

Methods: This mixed methods study involved two concurrent data collection phases, a qualitative phase with semi-structured interviews and a quantitative phase using an online survey. Neurologists (n=333) and APNs (n=135) were recruited from Canada, France, Germany, Italy, Spain, United Kingdom and the United States. All participants had to have a minimum of two years' experience in the care of pwMS and be currently active in clinical practice.

Results: A triangulated analysis of qualitative and quantitative data identified multiple challenges. For APNs, these mainly related to diagnosing MS, integrating new agents in their practice, sequential DMT selection, treatment monitoring and providing personalized care. Specifically, two-thirds of APNs reported no or basic knowledge of the 2017 McDonald criteria and over half reported a knowledge gap of new DMTs available (51%) and a skill gap when integrating them into practice (58%). APNs expressed a knowledge gap of treatment sequencing (46%) and a skill gap in making decisions about sequencing (62%). Forty-four percent of APNs reported a gap in their skills of integrating patient's goals into treatment recommendations. For neurologists, the main challenges included managing side effects, aligning care to their patient's personal goals and quality of life (QoL). Specifically, over a third of neurologists reported no or basic knowledge of the characteristics of treatment failure (35%), and 32% reported no or basic skills identifying treatment failure. Skills needed to integrate patient's individual goals into treatment recommendations were reported as none or low by 39% of neurologists. In addition, there were significant differences according to years of practice in the majority (9 out of 14) of confidence items with respect to discussing specific MS-related topics with patients. Significant differences between countries were also identified.

Conclusion: The complexity of diagnosing MS and the variety of available DMTs for pwMS lead to uncertainties, even among specialized healthcare professionals. These should be addressed through focused education and training to optimize care for pwMS.
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http://dx.doi.org/10.1016/j.msard.2021.102854DOI Listing
May 2021

Prenatal exposure to per- and polyfluoroalkyl substances and cognitive development in infancy and toddlerhood.

Environ Res 2021 05 26;196:110939. Epub 2021 Feb 26.

Department of Earth and Environmental Sciences, University of Texas, Arlington, TX, USA. Electronic address:

Background/objective: Per- and polyfluoroalkyl substances (PFAS) have neurobehavioral toxicity in experimental studies. Evidence on associations between prenatal PFAS exposure and child's cognitive development is inconsistent partly due to differences in assessment time points and tools. We examined associations of prenatal maternal serum PFAS concentrations with child's cognitive development assessed at multiple time points in infancy and toddlerhood.

Methods: We included 140 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a longitudinal cohort of children with a first degree relative who was diagnosed with autism spectrum disorder followed from birth. Study children's cognitive development was assessed at 6, 12, 24, and 36 months of age using the Mullen Scales of Early Learning (MSEL) which provides an overall Early Learning Composite (normative mean of 100 and SD of 15) and four subscales (i.e., fine motor, visual reception, receptive language, and expressive language abilities; normative mean of 50 and SD of 10). Nine PFAS were quantified in maternal serum collected during pregnancy. We examined associations of log 2-transformed prenatal maternal serum PFAS concentrations with the MSEL Composite and each of the subscale scores at each time point as well as longitudinal changes in the scores over the four time points. We also classified trajectories into low- and high-score groups and fit Poisson regression models to estimate associations expressed as relative risks (RR).

Results: Among six PFAS detected in more than 60% of the samples, prenatal maternal serum perfluorooctanoate (PFOA) was inversely associated with child's Composite score at 24 months (β = -5.22, 95% CI: -8.27, -2.17) and 36 months of age (β = -5.18, 95% CI: -9.46, -0.91), while other five PFAS were not strongly associated with Composite score at any time points. When assessing longitudinal changes in the scores over the four time points, PFOA was associated with trajectories having a negative slope for Composite scores and all four subscales. When examining trajectories of the scores between low- and high-score groups, PFOA was associated with having lower and/or decreasing Composite scores (RR = 1.49, 95% CI: 1.09, 2.03).

Conclusions: Prenatal PFOA appears to adversely affect child's cognitive development in toddlerhood in this study population. Because a large fraction of MARBLES children is at risk for atypical development, population-based studies are needed to confirm our findings.
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http://dx.doi.org/10.1016/j.envres.2021.110939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119322PMC
May 2021

Manifestations and impact of the COVID-19 pandemic in neuroinflammatory diseases.

Ann Clin Transl Neurol 2021 04 22;8(4):918-928. Epub 2021 Feb 22.

Multiple Sclerosis Center and Center for Translational & Computational Neuroimmunology, Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, New York, USA.

Objective: To report initial results of a planned multicenter year-long prospective study examining the risk and impact of COVID-19 among persons with neuroinflammatory disorders (NID), particularly multiple sclerosis (MS).

Methods: In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of suspected COVID-19 in persons with NID (PwNID) and change in their neurological care.

Results: Our cohort included 1115 participants (630 NID, 98% MS; 485 reference) as of 30 April 2020. 202 (18%) participants, residing in areas with high COVID-19 case prevalence, met the April 2020 CDC symptom criteria for suspected COVID-19, but only 4% of all participants received testing given testing shortages. Among all participants, those with suspected COVID-19 were younger, more racially diverse, and reported more depression and liver disease. PwNID had the same rate of suspected COVID-19 as the reference group. Early changes in disease management included telemedicine visits in 21% and treatment changes in 9% of PwNID. After adjusting for potential confounders, increasing neurological disability was associated with a greater likelihood of suspected COVID-19 (OR  = 1.45, 1.17-1.84).

Interpretations: Our study of real-time, patient-reported experience during the COVID-19 pandemic complements physician-reported MS case registries which capture an excess of severe cases. Overall, PwNID seem to have a risk of suspected COVID-19 similar to the reference population.
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http://dx.doi.org/10.1002/acn3.51314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013889PMC
April 2021

Mesenchymal stem cells genetically engineered to express platelet-derived growth factor and heme oxygenase-1 ameliorate osteoarthritis in a canine model.

J Orthop Surg Res 2021 Jan 11;16(1):43. Epub 2021 Jan 11.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.

Background: Mesenchymal stem cells (MSCs) are used for the treatment of osteoarthritis (OA), and MSC genetic engineering is expected to enhance cartilage repair. Here, we aimed to investigate the effect of MSCs overexpressing platelet-derived growth factor (PDGF) or heme oxygenase-1 (HO-1) in chondrocytes and synovial cells with an OA phenotype and assess the in vivo efficacy of intra-articular injections of these MSCs in canine OA models.

Methods: Canine adipose-derived MSCs were transfected with canine PDGF (PDGF-MSCs) or HO-1 (HO-1-MSCs) using lentiviral vectors. Canine chondrocytes or synovial cells were stimulated with lipopolysaccharide (LPS) to mimic the inflammatory OA model and then co-cultured with MSCs, PDGF-MSCs, or HO-1-MSCs for 24 h and 72 h. The mRNA levels of pro-inflammatory, extracellular matrix-degradative/synthetic, or pain-related factors were measured after co-culture by real-time PCR. Furthermore, a surgery-induced canine OA model was established and the dogs were randomized into four groups: normal saline (n = 4), MSCs (n = 4), PDGF-MSCs (n = 4), and HO-1-MSCs (n = 4). The OA symptoms, radiographic OA severity, and serum matrix metallopeptidase (MMP)-13 levels were assessed before and 10 weeks after treatment, to evaluate the safety and efficacy of the modified MSCs.

Results: PDGF or HO-1 overexpression significantly reduced the expression of pro-inflammatory factors, MMP-13, and nerve growth factor elicited by LPS and increased that of aggrecan and collagen type 2 in chondrocytes (P < 0.05). In addition, the expression of aggrecanases was significantly downregulated in synovial cells, whereas that of tissue inhibitor of metalloproteinases was upregulated (P < 0.05). Furthermore, the co-cultured MSCs highly expressed genes that contributed to the maintenance of joint homeostasis (P < 0.05). In vivo studies showed that OA symptoms improved after administration of all MSCs. Also, PDGF-MSCs significantly improved limb function and reduced pain (P < 0.05). The results of the radiographic assessment and serum MMP-13 levels did not vary significantly compared to those of the control.

Conclusions: Genetically modifying PDGF and HO-1 in MSCs is an effective strategy for treating OA, suggesting that PDGF-MSCs can be novel therapeutic agents for improving OA symptoms.
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http://dx.doi.org/10.1186/s13018-020-02178-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802278PMC
January 2021

Three-Dimensional Printing of Natural Materials Involving Loess-Based Composite Materials Designed for Ecofriendly Applications.

Materials (Basel) 2021 Jan 8;14(2). Epub 2021 Jan 8.

Department of Materials Science and Engineering, Hongik University, Seoul 04066, Korea.

In this work, loess-based materials were designed based on a multicomponent composite materials system for ecofriendly natural three-dimensional (3D) printing involving quick lime, gypsum, and water. The 3D printing process was monitored as a function of gypsum content; in terms of mechanical strength and electrical resistance, in the cube-shaped bulk form. After initial optimization, the 3D printing composition was refined to provide improved printability in a 3D printing system. The optimal 3D fabrication allowed for reproducible printing of rectangular columns and cubes. The development of 3D printing materials was scrutinized using a multitude of physicochemical probing tools, including X-ray diffraction for phase identification, impedance spectroscopy to monitor setting behaviors, and mercury intrusion porosimetry to extract the pore structure of loess-based composite materials. Additionally, the setting behavior in the loess-based composite materials was analyzed by investigating the formation of gypsum hydrates induced by chemical reaction between quick lime and water. This setting reaction provides reasonable mechanical strength that is sufficient to print loess-based pastes via 3D printing. Such mechanical strength allows utilization of robotic 3D printing applications that can be used to fabricate ecofriendly structures.
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http://dx.doi.org/10.3390/ma14020293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826633PMC
January 2021

Prenatal exposure to per- and polyfluoroalkyl substances in association with autism spectrum disorder in the MARBLES study.

Environ Int 2021 02 30;147:106328. Epub 2020 Dec 30.

Department of Earth and Environmental Sciences, University of Texas, Arlington, TX, USA. Electronic address:

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has shown potential to adversely affect child brain development, but epidemiologic evidence remains inconsistent. We examined whether prenatal exposure to PFAS was associated with increased risk of autism spectrum disorder (ASD).

Methods: Participants were 173 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a high-risk ASD cohort. At 3 years old, children were clinically confirmed for ASD and classified into ASD (n = 57) and typical development (TD, n = 116). We quantified nine PFAS in maternal serum collected during pregnancy. We examined associations of ASD with individual PFAS as well as the combined effect of PFAS on ASD using scores of the first principal component (PC-1) accounting for the largest variance.

Results: Prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) showed positive associations (per 2 nanogram per milliliter increase: relative risk (RR) = 1.20, 95% CI: 0.90, 1.61 [PFOA]; RR = 1.24, 95% CI: 0.91, 1.69 [PFNA]), while perfluorohexane sulfonate (PFHxS) showed a negative association (RR = 0.88, 95% CI: 0.77, 1.01) with ASD risk. When examining associations of ASD with untransformed PFAS concentrations, PFOA, PFNA, and PC-1 were associated with increased ASD risk (per nanogram per milliliter increase: RR = 1.31, 95% CI: 1.04, 1.65; RR = 1.79, 95% CI: 1.13, 2.85; RR = 1.10, 95% CI: 0.97, 1.25, respectively), while the RR of PFHxS moved toward the null.

Conclusions: From this high-risk ASD cohort, we observed increased risk of ASD in children exposed to PFOA and PFNA. Further studies should be conducted in the general population because this population may have a larger fraction of cases resulting from genetic sources.
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http://dx.doi.org/10.1016/j.envint.2020.106328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856021PMC
February 2021

Effect of an Educational Intervention on Therapeutic Inertia in Neurologists With Expertise in Multiple Sclerosis: A Randomized Clinical Trial.

JAMA Netw Open 2020 12 1;3(12):e2022227. Epub 2020 Dec 1.

Zurich Center for Neuroeconomics, Department of Economics, University of Zurich, Zurich, Switzerland.

Importance: Therapeutic inertia (TI) is the failure to escalate therapy when treatment goals are unmet and is associated with low tolerance to uncertainty and aversion to ambiguity in physician decision-making. Limited information is available on how physicians handle therapeutic decision-making in the context of uncertainty.

Objective: To evaluate whether an educational intervention decreases TI by reducing autonomic arousal response (pupil dilation), a proxy measure of how physicians respond to uncertainty during treatment decisions.

Design, Setting, And Participants: In this randomized clinical trial, 34 neurologists with expertise in multiple sclerosis (MS) practicing at 15 outpatient MS clinics in academic and community institutions from across Canada were enrolled. Participants were randomly assigned to receive an educational intervention that facilitates treatment decisions (active group) or to receive no exposure to the intervention (usual care [control group]) from December 2017 to March 2018. Participants listened to 20 audio-recorded simulated case scenarios as pupil responses were assessed by eye trackers. Autonomic arousal was assessed as pupil dilation in periods in which critical information was provided (first period [T1]: clinical data, second period [T2]: neurologic status, and third period [T3]: magnetic resonance imaging data). Data were analyzed from September 2018 to March 2020.

Interventions: The traffic light system (TLS)-based educational intervention vs usual care (unexposed). The TLS (use of established associations between traffic light colors and actions to stop or proceed) assists participants in identifying factors associated with worse prognosis in MS care, thereby facilitating the treatment decision-making process by use of established associations between red, green, and yellow colors and risk levels, and actions (treatment decisions).

Main Outcomes And Measures: Pupil assessment was the primary autonomic outcome. To test the treatment effect of the educational intervention (TLS), difference-in-differences models (also called untreated control group design with pretest and posttest) were used.

Results: Of 38 eligible participants, 34 (89.4%) neurologists completed the study. The mean (SD) age was 44.6 (11.6) years; 38.3% were female and 20 (58.8%) were MS specialists. Therapeutic inertia was present in 50.0% (17 of 34) of all participants and was associated with greater pupil dilation. For every additional SD of pupil dilation, the odds of TI increased by 51% for T1 (odds ratio, 1.51; 95% CI, 1.12-2.03), by 31% for T2 (odds ratio, 1.31; 95% CI, 1.08-1.59), and by 49% for T3 (odds ratio, 1.49; 95% CI, 1.13-1.97). The intervention significantly reduced TI (risk reduction, 31.5%; 95% CI, 16.1%-47.0%). Autonomic arousal responses mediated 29.0% of the effect of the educational intervention on TI.

Conclusions And Relevance: In this randomized clinical trial, the TLS intervention decreased TI as measured by pupil dilation, which suggests that individual autonomic arousal is an indicator of how physicians handle uncertainty when making live therapeutic decisions. Pupil response, a biomarker of TI, may eventually be useful in medical education.

Trial Registration: ClinicalTrials.gov Identifier: NCT03134794.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.22227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745101PMC
December 2020

An International Standardized Magnetic Resonance Imaging Protocol for Diagnosis and Follow-up of Patients with Multiple Sclerosis: Advocacy, Dissemination, and Implementation Strategies.

Int J MS Care 2020 Sep-Oct;22(5):226-232. Epub 2020 Oct 27.

Standardized magnetic resonance imaging (MRI) protocols are important for the diagnosis and monitoring of patients with multiple sclerosis (MS). The Consortium of Multiple Sclerosis Centers (CMSC) convened an international panel of MRI experts to review and update the current guidelines. The objective was to update the standardized MRI protocol and clinical guidelines for diagnosis and follow-up of MS and develop strategies for advocacy, dissemination, and implementation. Conference attendees included neurologists, radiologists, technologists, and imaging scientists with expertise in MS. Representatives from the CMSC, Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, US Department of Veteran Affairs, National Multiple Sclerosis Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis companies were present. Before the meeting, CMSC members were surveyed about standardized MRI protocols, gadolinium use, need for diffusion-weighted imaging, and the central vein sign. The panel worked to make the CMSC and MAGNIMS MRI protocols similar so that the updated guidelines could ultimately be accepted by international consensus. Advocacy efforts will promote the importance of standardized MS MRI protocols. Dissemination will include publications, meeting abstracts, educational programming, webinars, "meet the expert" teleconferences, and examination cards. Implementation will require comprehensive and coordinated efforts to make the protocol easy to access and use. The ultimate vision, and goal, is for the guidelines to be universally useful, usable, and used as the standard of care for patients with MS.
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http://dx.doi.org/10.7224/1537-2073.2020-094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643842PMC
October 2020

Mystery Case: Migraine, hearing loss, and blurred vision in a young woman.

Neurology 2020 11 12;95(21):e2945-e2950. Epub 2020 Oct 12.

From the Division of Neurology, Department of Medicine (S.S., J.A.M., J.O.), Department of Ophthalmology and Vision Sciences (J.A.M.), and St Michael's Hospital (J.A.M., J.O.), University of Toronto, Ontario, Canada.

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http://dx.doi.org/10.1212/WNL.0000000000011034DOI Listing
November 2020

Discovery of N-glycan Biomarkers for the Canine Osteoarthritis.

Life (Basel) 2020 Sep 14;10(9). Epub 2020 Sep 14.

Department of Food and Nutrition, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea.

Protein glycosylation is a post-translational modification that impacts on protein activity, stability, and interactions. It was sensitively altered by the cellular state and, therefore, is now used for a diagnostic or prognostic indicator of various human diseases such as cancer. To evaluate the clinical feasibility in the veterinary area, the N-glycan biomarkers were discovered from canine serum for the diagnosis of osteoarthritis (OA), which is one of the most common diseases of dogs. N-glycome was obtained from 20 μL of canine serum by the enzymatic cleavage followed by the purification and enrichment using solid-phase extraction. Independent compositions of 163 and 463 N-glycans were found from healthy control (n = 41) and osteoarthritis patients (n = 92), respectively. Initially, 31 of the potential biomarkers were screened by the -values below 1.0 × 10 from ANOVA. Then, the area under the curve (AUC) and the intensity ratio between OA patient and healthy control (P/C ratio) were calculated. Considering the diagnostic efficacy, the AUC bigger than 0.9 and the P/C ratio larger than 3.0 were used to discover 16 N-glycans as diagnostic biomarkers. Particularly, five of the diagnostic biomarkers were AUC above 0.99 and three of N-glycans had AUC 1.0. The results suggest a clear possibility for N-glycan biomarkers to be used as a clinical tool in the veterinary medical area enabling to provide objective and non-invasive diagnostic information.
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http://dx.doi.org/10.3390/life10090199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555374PMC
September 2020

Clinical and MRI characteristics of multiple sclerosis in patients of Middle Eastern and North African ancestry residing in Ontario, Canada.

Mult Scler 2021 06 11;27(7):1027-1036. Epub 2020 Aug 11.

Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Background: Multiple sclerosis (MS) incidence is rising in traditionally low-burden regions, including the Middle East and North Africa (MENA).

Objectives: Our objective was to evaluate disease characteristics in MS patients of MENA descent (MENA-MS).

Methods: MENA-MS patients and age- and sex-matched MS patients of European descent (EUR-MS) were identified through the MS Clinic Registry of St. Michael's Hospital in Toronto, Canada. Disease activity and severity were evaluated by the annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, change in the Expanded Disability Status Scale (EDSS), progression index (PI), and MS Severity Score (MSSS).

Results: All MS patients within the registry identified to be of MENA origin ( = 192), and age- and sex-matched EUR-MS patients were included. Mean age was 42.9 years, 67% female. A total of 25% and 24% of EUR-MS and MENA-MS had progressive disease, with similar mean disease durations (11.5 and 11.4 years, respectively). Clinical and radiological disease activity (ARR, proportion with new/enlarging MRI lesions) was similar. MENA-MS showed greater disability progression over time (EDSS change = 0.24 vs. 0.06,  = 0.01), a higher MSSS (3.12 vs. 2.67,  = 0.04), and higher PI (0.34 vs. 0.27,  = 0.07).

Conclusion: MENA-MS patients demonstrate higher disease severity compared to EUR-MS patients, despite having similar inflammatory measures of disease activity, with disability progression in the absence of relapses. These observations illustrate the importance of the intersections of environmental, socioeconomic, and genetic determinants in optimizing individualized MS care.
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http://dx.doi.org/10.1177/1352458520948212DOI Listing
June 2021

Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations.

Can J Neurol Sci 2020 07 6;47(4):437-455. Epub 2020 Apr 6.

The Hospital for Sick Children, Toronto, Ontario, Canada.

The Canadian Multiple Sclerosis Working Group has updated its treatment optimization recommendations (TORs) on the optimal use of disease-modifying therapies for patients with all forms of multiple sclerosis (MS). Recommendations provide guidance on initiating effective treatment early in the course of disease, monitoring response to therapy, and modifying or switching therapies to optimize disease control. The current TORs also address the treatment of pediatric MS, progressive MS and the identification and treatment of aggressive forms of the disease. Newer therapies offer improved efficacy, but also have potential safety concerns that must be adequately balanced, notably when treatment sequencing is considered. There are added discussions regarding the management of pregnancy, the future potential of biomarkers and consideration as to when it may be prudent to stop therapy. These TORs are meant to be used and interpreted by all neurologists with a special interest in the management of MS.
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http://dx.doi.org/10.1017/cjn.2020.66DOI Listing
July 2020

Pregnancy outcomes and postpartum relapse rates in women with RRMS treated with alemtuzumab in the phase 2 and 3 clinical development program over 16 years.

Mult Scler Relat Disord 2020 Aug 6;43:102146. Epub 2020 May 6.

University of Cambridge, Cambridge, United Kingdom. Electronic address:

Background: Relapsing-remitting multiple sclerosis (RRMS) is frequently diagnosed in women of reproductive age. Because the use of disease-modifying therapies (DMTs) early in the disease course is increasing, it is important to evaluate the safety of DMTs in pregnant women and their developing fetuses. Alemtuzumab, approved for the treatment of relapsing forms of MS, is administered as 2 courses of 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Alemtuzumab is eliminated from the body within approximately 30 days after administration; it is recommended that women of childbearing potential use effective contraception during and for 4 months after treatment. Here, we report pregnancy outcomes in alemtuzumab-treated women from the phase 2 and 3 clinical development program over 16 years.

Methods: We followed 972 women who had alemtuzumab in phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies, and/or in 2 consecutive extension studies (NCT00930553; NCT02255656 [TOPAZ]). In the extension studies, patients could receive additional alemtuzumab (12 mg/day on 3 days; ≥12 months apart) as needed for disease activity. All women who received alemtuzumab in the clinical development program were included. Pregnant or lactating patients were followed up for safety.

Results: As of November 26, 2018, 264 pregnancies occurred in 160 alemtuzumab-treated women, with a mean age at conception of 32.6 years, and mean time from last alemtuzumab dose to conception of 35.9 months. Of the 264 pregnancies, 233 (88%) were completed, 11 (4%) were ongoing, and 20 (8%) had unknown outcomes; 16 (6%) conceptions occurred within 4 months, and 5 conceptions within 1 month of the last alemtuzumab dose. Of the 233 completed pregnancies with known outcomes, there were 155 (67%) live births with no congenital abnormalities or birth defects, 52 (22%) spontaneous abortions, 25 (11%) elective abortions, and 1 (0.4%) stillbirth. Maternal age was associated with an increased risk of spontaneous abortion in alemtuzumab-treated patients (<35 years: 15%; ≥35 years: 37%; relative risk [RR], 2.46 [95% CI: 1.53-3.95], p=0.0002). Risk of spontaneous abortion was not increased in patients becoming pregnant ≤4 months versus >4 months since alemtuzumab exposure (19% vs 23%; RR, 1.08 [95% CI: 0.41-2.85], p=0.88). Autoimmune thyroid adverse events did not increase risk for spontaneous abortion (patients with vs without thyroid adverse events, 23.7% vs 21.3%; RR, 1.11 [95% CI: 0.69-1.80], p=0.75). Annualized relapse rate was 0.10 and 0.12 in the 2 years prior to pregnancy (post alemtuzumab), and was 0.22, 0.12, and 0.12 in each of the first 3 years postpartum, respectively.

Conclusion: Normal live births were the most common outcome in women exposed to alemtuzumab 12 mg or 24 mg in clinical studies. Spontaneous abortion rate in alemtuzumab-treated patients was comparable with rates in the general population and treatment-naive MS patients, and was not increased in women with pregnancy onset within 4 months of alemtuzumab exposure. There was a minimal increase in postpartum relapses.
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http://dx.doi.org/10.1016/j.msard.2020.102146DOI Listing
August 2020
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