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Publications (235)
The capacity to regenerate myelin in the central nervous system diminishes with age. This decline is particularly evident in multiple sclerosis (MS), a chronic demyelinating disease. Whether cellular senescence, a hallmark of aging, contributes to remyelination impairment remains unknown. Here, we show that senescent cells accumulate within demyeli...
Background and objectives: The literature on severe West Nile virus (WNV) neuroinvasive disease (WNND) in patients treated with anti-CD20 therapies is limited to case reports. We systematically characterize cases of WNND in the tertiary academic UCHealth system.
Methods: A retrospective cohort (January 2016 to January 2024) of patients with a valid...
Background and Objectives
Immune checkpoint inhibitors (ICIs) are increasingly used against various cancers but are associated with immune-related adverse events (irAEs). Risk of irAEs may be higher in patients with certain preexisting autoimmune diseases, and these patients may also experience exacerbation of the underlying autoimmune disease foll...
Background
Ublituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity. The phase 3 ULTIMATE I and II studies showed significant improvements in annualized relapse rate, total number of gadolinium-enhancing (Gd+) T1 lesions, and total number of new or enlarging T2 at Week 96, as well as...
Objectives
To evaluate the prognostic value of 3- and 12-month on-treatment serum neurofilament light chain (sNfL) levels for future disease activity in with relapsing multiple sclerosis[pwRMS]
Methods
A baseline sNfL cut-off was predefined by the median sNfL value across the ofatumumab ASCLEPIOS I/II Phase 3 clinical trials and participants were...
Emerging evidence is encouraging and suggests that a substantial proportion of patients without antibody responses (due to anti-CD20 therapy or other etiologies) to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines develop T cell responses. However, antigen-specific T cellular responses are notoriously difficult to assess clinic...
Objectives: We describe the development of Your Multiple Sclerosis Questionnaire and present the real-world usability testing results of Your Multiple Sclerosis Questionnaire.
Methods: The Your Multiple Sclerosis Questionnaire tool was developed in four stages to collect feedback from people living with MS (plwMS), patient organizations, and clin...
Aim
Evaluate the real-world costs over two years and costs by site of care for ocrelizumab (OCR), natalizumab (NTZ), and alemtuzumab (ATZ) in patients with multiple sclerosis (MS).
Methods
This retrospective study used HealthCore Integrated Research Database and included continuously enrolled adults with MS initiating OCR, NTZ, and ATZ between Apr...
Objective:
This study aimed to evaluate safety (infusion-related reactions [IRRs]) and patient satisfaction (patient-reported outcomes [PROs]) for at-home ocrelizumab administration for patients with multiple sclerosis (MS).
Methods:
This open-label study included adult patients with an MS diagnosis who had completed a ≥ 600-mg ocrelizumab dose,...
Background:
The monoclonal antibody ublituximab enhances antibody-dependent cellular cytolysis and produces B-cell depletion. Ublituximab is being evaluated for the treatment of relapsing multiple sclerosis.
Methods:
In two identical, phase 3, double-blind, double-dummy trials (ULTIMATE I and II), participants with relapsing multiple sclerosis w...
Background
Treatment with natalizumab once every 4 weeks is approved for patients with relapsing-remitting multiple sclerosis, but is associated with a risk of progressive multifocal leukoencephalopathy. Switching to extended-interval dosing is associated with lower progressive multifocal leukoencephalopathy risk, but the efficacy of this approach...
Objective
To evaluate plasma neurofilament light (NfL) levels in autoimmune neurologic disorders (AINDs) and autoimmune encephalitis (AE).
Background
Each particular neural autoantibody syndrome has a different clinical phenotype, making one unifying clinical outcome measure difficult to assess. While this is a heterogeneous group of disorders, th...
Background
Strategies for sequencing disease modifying therapies (DMTs) in multiple sclerosis (MS) patients include escalation, high efficacy early, induction, and de-escalation.
Objective
To provide a perspective on de-escalation, which aims to match the ratio of DMT benefit/risk in aging patients.
Methods
We reanalyzed data from a retrospective...
Background
Ocrelizumab and rituximab are frequently used treatments for multiple sclerosis (MS). Data on switching from rituximab to ocrelizumab is limited.
Objectives
To assess the frequency, severity, and factors of infusion related reactions (IRRs) in patients with MS who switch from rituximab to ocrelizumab, compared to those who stay on ritux...
Ublituximab is a novel anti-CD20 therapy developed for the treatment of patients with multiple sclerosis. It is a glycoengineered chimeric antibody with a novel epitope on CD20, with high antibody-dependent cell-mediated cytotoxicity. Maintenance doses are administered every 6 months over an hour, providing a convenient dosing regimen. The identica...
Declines in motor function are closely associated with decreases in sensory function in multiple sclerosis (MS). The purpose of our study was to assess the changes in motor function and disability status elicited by transcutaneous electrical nerve stimulation (TENS) to limb muscles of individuals with MS. Fifteen persons with MS and 11 age-matched...
Fatigue is one of the most common debilitating symptoms reported by persons with multiple sclerosis (MS). It reflects feelings of tiredness, lack of energy, low motivation, and difficulty in concentrating. It can be measured at a specific instant in time as a perception that arises from interoceptive networks involved in the regulation of homeostas...
Purpose of Review
This review presents the hypothesis that loss of neurologic reserve explains onset of progressive multiple sclerosis (PrMS).
Recent Findings
Evidence supporting the separate classification of PrMS and relapsing multiple sclerosis (RMS) is limited and does not explain PrMS or the response of these patients to therapy.
Summary
We...
Background
: Clinically stable multiple sclerosis (MS) patients often have negligible inflammatory MRI changes. Brain atrophy may provide insight into subclinical disease progression. The objective was to compare brain atrophy rates in stable patients on long term natalizumab treatment vs. age and gender matched healthy non-MS controls (HC) prospec...
Background
Delayed-release dimethyl fumarate (DMF) has demonstrated robust efficacy in treating patients with relapsing-remitting multiple sclerosis. Decreases in absolute lymphocyte count (ALC) are a well-known pharmacodynamic effect of DMF treatment, but lymphocyte recovery dynamics are not well characterized after discontinuation of DMF.
Method...
Background
We describe KPMW135, a novel CD20 x CD3 bispecific molecule, in which a CD3-directed ScFv (SP34) is conjugated to rituximab (RTX). RTX is a chimeric monoclonal antibody (mAb) specific for CD20, used to treat B-cell lymphomas and lymphocytic leukemias. Monoclonal Ab therapy enhancer (MATE™) enables efficient site-directed chemical conjuga...
Background
We describe KPMW101, which was created by chemical conjugation of a CD38-specific binder to clinical grade intravenous immunoglobulin (IvIg) pooled from healthy donors. Kleo’s MATE TM technology enables efficient site-directed chemical conjugation to ‘off-the-shelf’ IvIg and allows the development of antitumor agents with rapidly introdu...
Background: Clinically stable multiple sclerosis (MS) patients on long-term therapy often have negligible acute inflammation on MRI. Brain atrophy may provide insight into subclinical disease progression in such populations.
Objective: This study aims to compare brain atrophy for age- and gender-matched MS patients treated for >2 years with fingoli...
Introduction
Limited comparative effectiveness data for rituximab (RTX) versus natalizumab (NTZ), fingolimod (FTY), and dimethyl fumarate (DMF) for the treatment of multiple sclerosis (MS) exist.
Methods
Clinician‐reported data on patients prescribed RTX, NTZ, FTY, or DMF for the treatment of MS at the Rocky Mountain MS Center at the University of...
Introduction
Studies investigating rates and risk factors for serious safety events (SSEs) during rituximab treatment of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and related disorders are limited.
Methods
Rituximab‐treated patients with MS, NMOSD, or related disorders at the Rocky Mountain and New York University M...
Background
: Ocrelizumab is an approved MS treatment administered as two 300-mg intravenous infusions 2 weeks apart (Dose 1), each lasting approximately 2.5 hours, followed by single 600-mg infusions every 6 months lasting approximately 3.5 hours. Our objective was to evaluate shorter-duration ocrelizumab infusions in the Phase IIIb open-label SaRO...
psicología desde el caribe issn 0123-417x (impreso) issn 2011-7485 (on line) Vol. 32, n.° 3, septiembre-diciembre 2015 http://dx. El objetivo de este estudio fue conocer las características de la práctica neuropsicológica en México, incluyendo la formación profesional, la situación laboral actual, el proceso de evalua-ción y diagnóstico, rehabilita...
The ‘cancer cell fusion’ theory is controversial due to the lack of methods available to identify hybrid cells and to follow the phenomenon in patients. However, it seems to be one of the best explanations for both the origin and metastasis of primary tumors. Herein, we co-cultured lung cancer stem cells with human monocytes and analyzed the dynami...
Background: Cognitive dysfunction is a disabling sequela of multiple sclerosis (MS), and brain volume loss has been associated with disease progression, disability, and cognitive dysfunction. (1) The association between self-reported subjective cognitive concerns (SCC) and objective cognitive performance (OCP) in MS remains uncertain. (2-4) Objecti...
Background:
Antibody recruiting molecules (ARM) are novel, immunotherapeutic bifunctional molecules composed of two active termini connected by a linker. One of the termini binds to a target molecule on a cancer cell. The other terminus, called universal antibody binding terminus (uABT), recruit all endogenous IgG antibodies independent of their an...
Background:
Antibody recruiting molecules (ARM) represent a new modality in immunotherapy of cancer. These are bifunctional molecules composed of two active termini connected by a linker. One of the termini binds to a target molecule on a cancer cell. The other terminus can recruit endogenous IgG antibodies independent of their antigen binding spec...
Background:
Multiple sclerosis (MS) symptoms reported in the first year of the disease include sensory impairment, fatigue, reduced mobility, and declines in hand function. The progressive reduction in motor function experienced by persons living with MS is invariably preceded by changes in sensory processing, which are strongly associated with th...
Background:
Dimethyl fumarate (DMF) and fingolimod (FTY) are approved oral disease modifying therapies (DMTs) for relapsing multiple sclerosis (MS). There are currently no known head-to-head studies comparing DMF and FTY over 36 months, which leaves their relative effectiveness unknown.
Objective:
To assess real-world discontinuation, effectiven...
Background:
Patient-reported outcome (PRO) measures have been shown to be effective for tracking treatment outcomes in multiple sclerosis (MS). However, collecting PROs as part of the clinical standard of care can be time-consuming and examination of their validity for use in an MS sample has been limited.
Objective:
To determine the discriminan...
Rituximab is a chimeric anti-CD20 monoclonal antibody that is an effective therapy for multiple sclerosis. Rituximab has been associated with the development of serum sickness (type III hypersensitivity) characterized by arthralgia, fever, and rash during the treatment of other conditions, such as rheumatoid arthritis. Here we describe serum sickne...
Natural killer cells (NK cells) are emerging as powerful mediators of anti-tumor effects in many cancer immunotherapy modalities.A multitude of these targeting strategies, however, cannot avoid cross-reactivity and potential NK cell depletion is a result of treatment. Furthermore, some therapies aim to directly engage surface receptors expressed by...
The global incidence of multiple sclerosis (MS) appears to be increasing. Although it may not be associated with a high mortality rate, this disease has a high morbidity rate which affects the quality of life of patients and reduces their ability to do their activities of daily living. Thankfully, the development of novel disease modifying therapie...
Full text: https://journals.sagepub.com/doi/full/10.1177/2055217319827618
Objective: Brain atrophy has been correlated with objective cognitive dysfunction in multiple sclerosis but few studies have explored self-reported subjective cognitive concerns and their relationship to brain volume changes. This study explores the relationship between subj...
Introduction
Delayed-release dimethyl fumarate (DMF) is an effective treatment for multiple sclerosis (MS). Some patients experience gastrointestinal (GI) adverse events (AEs) that may lead to premature DMF discontinuation. This study characterized the impact of site-specific GI management strategies on the occurrence of GI events and discontinuati...
Objective:
To examine whether rituximab induction followed by glatiramer acetate (GA) monotherapy is more effective than GA alone for the treatment of relapsing multiple sclerosis with active disease.
Methods:
This was a single-center, double-blind, placebo-controlled study. Fifty-five participants were randomly assigned (1:1 ratio) to either ri...
Objective
To compare 2‐year effectiveness and discontinuation of natalizumab (NTZ) versus fingolimod (FTY) and dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS).
Methods
Patients prescribed NTZ, FTY, or DMF at the Rocky Mountain MS Center at University of Colorado were identified. Clinician‐reported data were retrospectively coll...
Figure S1. Additional analyses including Cohen's D plots, individual effectiveness outcomes, subgroup analyses and time to event analyses.
Figure S2. Comparison of dose distributions calculated on planning CT (left) and repeat CT (right).
Figure S3. Unadjusted effectiveness outcomes occurring between 6 and 24 months for natalizumab (NTZ), fingoli...
Background
Studies suggest cannabis may improve symptoms like pain and muscle spasticity in patients with multiple sclerosis (PwMS). Despite cannabis’ new-found legality and availability, few studies have explored the profile of PwMS cannabis users and characteristics of their use, particularly in a state where cannabis is legal both for recreation...
Background
The effectiveness of fingolimod on clinical and magnetic resonance imaging (MRI) outcomes in patients with multiple sclerosis (MS) has been well established in trials and, to a lesser extent, in the real world.
Objective
To evaluate clinical and MRI outcomes in patients with relapsing MS receiving fingolimod in US clinical practice.
Me...
Background
There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood–brain barrier, with potential salutary effects in progressive multiple sclerosis.
Methods
We enrolled patients with pri...
Background
Dimethyl fumarate (DMF) and fingolimod (FTY) are approved oral disease-modifying therapies for relapsing multiple sclerosis (MS). Observational studies are valuable when randomized clinical trials cannot be done due to ethical or practical reasons. Two-site studies allow investigators to further ascertain external validity of previously...
BACKGROUND AND PURPOSE
Evidence is needed to understand the effect of fingolimod on slowing down brain atrophy progression in multiple sclerosis (MS) patients in clinical practice. We investigated the effect of fingolimod on brain atrophy in MS patients with active disease (clinically and/or magnetic resonance imaging [MRI]) versus no evidence of a...
