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Clinical and Translational Science May 2024No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and... (Review)
Review
No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and primary end points (PEs) of phase II and III trials intended to modify the natural course of the disease in patients with RMS. The purpose of the study is to explore trends/topics and discussion points in clinical trial design and PE, comparing them to regulatory guidelines and expert recommendations. Three trial registration systems, ClinicalTrials.gov, the EU Clinical Trials Register, and the Japan Registry of Clinical Trials, were used and 60 trials were evaluated. The dominant clinical trial design was a randomized controlled parallel-arms trial and other details were as follows: in adult phase III confirmatory trials (n = 32), active-controlled double-blind trial (DBT) (53%) and active-controlled open-label assessor-masking trial (16%); in adult phase II dose-finding trials (n = 9), placebo- and active-controlled DBT (44%), placebo-controlled DBT (22%), and placebo-controlled add-on DBT (22%); and in pediatric phase III confirmatory trials (n = 8), active-controlled DBT (38%) and active-controlled open-label non-masking trial (25%). The most common PEs were as follows: in adult confirmatory trials, annual relapse rate (ARR) (56%) and no evidence of disease activity-3 (NEDA-3) (13%); in adult dose-finding trials, the cumulative number of T1 gadolinium-enhancing lesions (56%), combined unique active lesions (22%), and overall disability response score (22%); and in pediatric confirmatory trials, ARR (38%) and time to first relapse (25%). It was suggested that some parts of the regulatory guidelines and expert recommendations need to be revised.
Topics: Humans; Clinical Trials, Phase III as Topic; Clinical Trials, Phase II as Topic; Adult; Multiple Sclerosis, Relapsing-Remitting; Child; Research Design; Endpoint Determination; Randomized Controlled Trials as Topic
PubMed: 38708586
DOI: 10.1111/cts.13794 -
Multiple Sclerosis and Related Disorders Nov 2023People with Multiple Sclerosis (pwMS) search for information online about various aspects of living with their disease, but details about patterns of searching and... (Review)
Review
BACKGROUND
People with Multiple Sclerosis (pwMS) search for information online about various aspects of living with their disease, but details about patterns of searching and outcomes are unclear. This means that opportunities to leverage online resources to support pwMS, and to enhance shared decision making, may be missed. We aimed to do a systematic review of the literature on digital information searching by pwMS.
METHODS
We performed a systematic search for studies assessing online information seeking of pwMS in MEDLINE and JSTOR databases. Studies were screened and selected by two investigators. All study designs were included, risk of bias was assessed using the Critical Appraisal Skills Programme qualitative checklist. Reports were assessed for the proportion of patients searching information online about MS, type of information sought, online tools used by patients, perceived quality of the information acquired, and impact of online searching in pwMS.
RESULTS
We identified 5 studies, including 10,090 patients. Most pwMS search for information online (53.8-82 %), which they rarely discuss with physicians. The most common topics are treatment, general disease information, symptoms, lifestyle recommendations, prognosis, and coping strategies. Patients that are younger, have a shorter disease duration, primary progressive MS, and during periods of disease worsening, are more likely to use online resources. Online information is perceived as low quality by pwMS.
CONCLUSIONS
Online information search is prevalent among pwMS. Despite concerns with the quality of the available information, only a minority of pwMS will discuss the information found with their physician. These findings highlight the importance of developing and providing quality online information resources for pwMS.
Topics: Humans; Multiple Sclerosis; Prognosis; Decision Making, Shared; Research Design; Patients
PubMed: 37801957
DOI: 10.1016/j.msard.2023.105032 -
Journal of Managed Care & Specialty... Dec 2023Multiple sclerosis (MS) is chronic progressive disease that poses a significant economic burden to patients and health care systems in the United States. We conducted a... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is chronic progressive disease that poses a significant economic burden to patients and health care systems in the United States. We conducted a systematic literature review to provide up-to-date insights on the economic burden of MS in the United States.
OBJECTIVE
To comprehensively review and summarize the latest published evidence on the economic burden of MS with a focus on cost, resource use, and work productivity.
METHODS
A systematic literature search was conducted using the Embase and Medline databases to identify studies, published between January 2011 and July 2022, reporting cost, resource use, or work productivity outcomes among people with MS in the United States. Clinical trials, economic modeling studies, and review articles were excluded. Details of eligible studies, including study design, patient population, and study outcomes for the overall population, as well as subgroups of interest, were extracted and summarized qualitatively.
RESULTS
Overall, 65 studies reporting cost, resource use, or work productivity data were included with majority of studies using claims data. The direct costs associated with MS ranged from $16,614 (2006) to $72,744 (2017) per patient per year with diseasemodifying therapies (DMTs) being the major cost contributors accounting for 43%-78%. The indirect costs reported ranged from $9,122 (2017) to $30,601 (2011) per patient per year with absenteeism, early retirement, and informal care being the key drivers for indirect costs. Costs, resource use, and work impairment were significantly higher for patients with severe disability compared with those with mild disability. Pharmacy costs were the major cost drivers in patients with mild, moderate, and severe disability. Similarly, patients with relapses incurred significantly higher costs, resource use, and work impairment compared with those without relapses. Additional hospitalization charges were the major driver of higher costs in patients who experienced relapses compared with those without relapses.
CONCLUSIONS
Direct costs, particularly DMTs, appear to be the major cost drivers for people with MS in the United States. Availability of lower-cost therapies may considerably decrease the economic burden on these patients and the health care systems. Future research focusing on indirect costs, intangible costs, and their contributors would contribute to further understanding of economic burden to avoid underestimation of the financial burden experienced by the patients.
Topics: Humans; United States; Multiple Sclerosis; Financial Stress; Cost of Illness; Chronic Disease; Recurrence; Health Care Costs
PubMed: 37976077
DOI: 10.18553/jmcp.2023.23039 -
Biomedicine & Pharmacotherapy =... Aug 2023Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease, but it is one of the most common inflammatory neuropathies in the population. It is... (Review)
Review
BACKGROUND
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease, but it is one of the most common inflammatory neuropathies in the population. It is particularly common among patients with diabetes mellitus. This raises many problems, both with the differential diagnosis of diabetic and inflammatory neuropathy, as well as the choice of treatment. Intravenous immunoglobulin (IVIG) is one of the therapeutic options. There is evidence for the effectiveness of IVIG in treating about two-thirds of patients. However, no review has been published to date systematising studies evaluating the response to IVIG treatment in patients with CIDP and coexisting diabetes.
METHODS
The present study is based on the PRISMA statement and is registered at PROSPERO (CRD42022356180). The study included searches of the databases of MEDLINE, ERIC, CINAHL Complete, Academic Search Ultimate and Health Source: Nursing/Academic Edition, finally including seven original papers evaluating a total of 534 patients in the review. The main inclusion criteria were the presence of a group of patients with CIDP and comorbid diabetes in the study.
RESULTS
The systematic review showed a lower efficacy of IVIG treatment among patients with coexisting diabetes compared with idiopathic CIDP (61 % vs 71 %). In addition, the presence of conduction blocks on neurography and shorter disease duration proved to be significant factors improving response to treatment.
CONCLUSIONS
Current scientific data do not allow for strong recommendations on the choice of treatment for CIDP. A randomised, multicentre study evaluating the efficacy of different therapeutic approaches to this disease entity needs to be planned.
Topics: Humans; Immunoglobulins, Intravenous; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Infusions, Intravenous; Administration, Intravenous; Diabetes Mellitus; Multicenter Studies as Topic
PubMed: 37290187
DOI: 10.1016/j.biopha.2023.114974 -
BMC Neurology Sep 2023Miller Fisher syndrome (MFS) is a subtype of Guillain-Barré syndrome (GBS) which is characterized by the three components of ophthalmoplegia, ataxia, and areflexia....
BACKGROUND
Miller Fisher syndrome (MFS) is a subtype of Guillain-Barré syndrome (GBS) which is characterized by the three components of ophthalmoplegia, ataxia, and areflexia. Some studies reported MFS as an adverse effect of the COVID-19 vaccination. We aimed to have a detailed evaluation on demographic, clinical, and para-clinical characteristics of subjects with MFS after receiving COVID-19 vaccines.
MATERIALS AND METHODS
A thorough search strategy was designed, and PubMed, Web of Science, and Embase were searched to find relevant articles. Each screening step was done by twice, and in case of disagreement, another author was consulted. Data on different characteristics of the patients and types of the vaccines were extracted. The risk of bias of the studies was assessed using Joanna Briggs Institute (JBI) tools.
RESULTS
In this study, 15 patients were identified from 15 case studies. The median age of the patients was 64, ranging from 24 to 84 years. Ten patients (66.6%) were men and Pfizer made up 46.7% of the injected vaccines. The median time from vaccination to symptoms onset was 14 days and varied from 7 to 35 days. Furthermore,14 patients had ocular signs, and 78.3% (11/14) of ocular manifestations were bilateral. Among neurological conditions, other than MFS triad, facial weakness or facial nerve palsy was the most frequently reported side effect that was in seven (46.7%) subjects. Intravenous immunoglobulin (IVIg) was the most frequently used treatment (13/15, 86.7%). Six patients received 0.4 g/kg and the four had 2 g/kg. Patients stayed at the hospital from five to 51 days. No fatal outcomes were reported. Finally, 40.0% (4/15) of patients completely recovered, and the rest experienced improvement.
CONCLUSION
MFS after COVID-19 immunization has favorable outcomes and good prognosis. However, long interval from disease presentation to treatment in some studies indicates that more attention should be paid to MFS as the adverse effect of the vaccination. Due to the challenging diagnosis, MFS must be considered in list of the differential diagnosis in patients with a history of recent COVID-19 vaccination and any of the ocular complaints, ataxia, or loss of reflexes, specially for male patients in their 60s and 70s.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Young Adult; Ataxia; COVID-19; COVID-19 Vaccines; Drug-Related Side Effects and Adverse Reactions; Facial Paralysis; Miller Fisher Syndrome; Prognosis; Vaccination
PubMed: 37735648
DOI: 10.1186/s12883-023-03375-4 -
Eye (London, England) Oct 2023To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support... (Review)
Review
OBJECTIVE
To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.
METHODS
We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).
RESULTS
From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.
CONCLUSION
There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.
Topics: Humans; Adult; Quality of Life; Reproducibility of Results; Optic Neuritis; Surveys and Questionnaires; Patient Reported Outcome Measures; Multiple Sclerosis
PubMed: 36932161
DOI: 10.1038/s41433-023-02478-z -
Neurologia 2023This article analyses the presence of gender bias in clinical trials of monoclonal antibodies used to treat multiple sclerosis. (Review)
Review
INTRODUCTION
This article analyses the presence of gender bias in clinical trials of monoclonal antibodies used to treat multiple sclerosis.
MATERIAL AND METHODS
We performed a systematic review of controlled clinical trials of 4 monoclonal antibodies used to treat multiple sclerosis (natalizumab, rituximab, alemtuzumab, and ocrelizumab). We searched the PubMed/MEDLINE database for articles published in English before March 2020. The study was conducted in accordance with the relevant international recommendations.
RESULTS
The search identified 89 articles, 55 of which met the inclusion criteria. Of all patients included in these trials, 64.6% were women. The lead authors of 10 of the studies were women. Fifteen of the 55 studies included a sex-based analysis of the primary endpoint. Only 8 articles discussed the results separately for men and for women.
CONCLUSIONS
The clinical trials of these 4 monoclonal antibodies present a significant gender bias. In most cases, the primary and secondary endpoints are not analyzed according to patient sex, despite the fact that international recommendations include this as a minimum requirement for ensuring scientific validity and obtaining appropriate results for extrapolation to the wider population.
Topics: Humans; Female; Male; Antibodies, Monoclonal; Multiple Sclerosis; Sexism; Alemtuzumab; Rituximab
PubMed: 37996214
DOI: 10.1016/j.nrleng.2021.01.008 -
Frontiers in Immunology 2023Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease...
BACKGROUND AND PURPOSE
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease of the central nervous system. The clinical features and prognosis of MOGAD adult cerebral cortical encephalitis (adult CCE) have not been fully elucidated. This study aims to further characterize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of CCE with anti-MOG antibody.
METHODS
We present two adult cases of CCE with anti-MOG antibody and summarize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of this phenotype as per a completed systematic review of the literature.
RESULTS
We found a total of 39 cases of MOGAD adult CCE (36% females; average age of onset of 29 years). Among them, 85% had seizure, 82% had headache, 64% had cortical symptoms, 64% had fever, 54% had changes of consciousness, and 38% had ocular symptoms. All cases demonstrated cerebral cortical T2 fluid-attenuated inversion recovery (FLAIR) lesions on MRI. Of the 25 patients (with seizure or not) who had EEG reports, 76% of patients showed abnormal EEG. Cerebrospinal fluid (CSF) white blood cell count of 90% of patients and CSF total protein of 67% of patients were elevated. In 16 patients with available CSF cytology data, 11 (69%) had abnormal cytology findings with monocytic predominance. In the 15 cases for which MOG antibody IgG was tested in both serum and CSF, 14 (93%) demonstrated a higher positive MOG IgG titer in serum than CSF. The majority of patients were treated with immunosuppressive therapy (97% corticosteroids, 15% mycophenolate mofetil, 13% IVIg, 5% azathioprine, and 5% other). The majority of patients had a favorable prognosis after treatment, as exemplified by improved clinical symptoms and imaging. Two patients relapsed.
CONCLUSIONS
The clinical presentation and prognosis of adult CCE remain less understood in comparison to more common MOGAD phenotypes. It is important to consider MOGAD as an underlying etiology for adult CCE, as early detection and immunotherapy may improve outcomes.
Topics: Female; Male; Humans; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Encephalitis; Seizures; Immunoglobulin G; Oligodendroglia
PubMed: 37520572
DOI: 10.3389/fimmu.2023.1203615 -
NeuroImage. Clinical 2024Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice.
OBJECTIVE
We performed a systematic review and meta-analysis on the use of QSM in MS.
METHODS
Our review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively.
RESULTS
After outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39-0.70, I = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19-0.57, I = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28-0.67, I = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = -0.39, 95 % CI = -0.66--0.12, I = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16-0.53, I = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions.
CONCLUSIONS
We could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine.
Topics: Humans; Multiple Sclerosis; Magnetic Resonance Imaging; Gray Matter; Brain
PubMed: 38582068
DOI: 10.1016/j.nicl.2024.103598 -
Revista de Neurologia Aug 2023While part of the care for neurological patients is done by telephone, it is not well known what neurological diseases and which part of that care is provided by...
INTRODUCTION AND OBJECTIVE
While part of the care for neurological patients is done by telephone, it is not well known what neurological diseases and which part of that care is provided by telephone. Our goal is to find it out through a bibliographic review.
MATERIALS AND METHODS
References on telephone care for neurological diseases accessible through the PubMed, Embase, and Cochrane platforms have been systematically reviewed, with an unspecified start date and up to March 2022. We found 618 references, and as 219 did not pass the exclusion criteria, 399 were finally included in the review.
RESULTS
Dementia is the area of neurology with more publications about its telephone assistance. It is followed by stroke, head trauma, multiple sclerosis, Parkinson's disease and movement disorders, epilepsy, neuromuscular disorders, and others.
DISCUSSION AND CONCLUSIONS
Dementias are the diseases with more bibliographic references on their telephone assistance despite not being the most prevalent. The telephone is frequently used to administer diagnostic scales or support caregivers and is particularly useful in diseases that limit mobility and attending a medical practice.
Topics: Humans; Neurology; Multiple Sclerosis; Epilepsy; Telephone; Parkinson Disease
PubMed: 37466132
DOI: 10.33588/rn.7703.2022284