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Annals of Clinical and Translational... Mar 2023Across its clinical development program, ocrelizumab demonstrated efficacy in improving clinical outcomes in multiple sclerosis, including annualized relapse rates and... (Review)
Review
Across its clinical development program, ocrelizumab demonstrated efficacy in improving clinical outcomes in multiple sclerosis, including annualized relapse rates and confirmed disability progression. However, as with any new treatment, it was unclear how this efficacy would translate into real-world clinical practice. The objective of this study was to systematically collate the published real-world clinical effectiveness data for ocrelizumab in relapsing remitting multiple sclerosis and primary progressive multiple sclerosis. A search strategy was developed in MEDLINE and Embase to identify articles reporting real-world evidence in people with relapsing remitting multiple sclerosis or primary progressive multiple sclerosis receiving treatment with ocrelizumab. The search focused on English language articles only but was not limited by the country in which the study was conducted or the time frame of the study. Additional manual searches of relevant websites were also performed. Fifty-two studies were identified reporting relevant evidence. Real-world effectiveness data for ocrelizumab were consistently favorable, with reductions in relapse rate and disease progression rates similar to those reported in the OPERA I/OPERA II and ORATORIO clinical trials, including in studies with more diverse patient populations not well represented in the pivotal trials. Although direct comparisons are confounded by lack of randomization of treatments, outcomes reported suggest that ocrelizumab has a similar or greater efficacy than other therapy options. Initial real-world effectiveness data for ocrelizumab appear favorable and consistent with results reported in clinical trials, providing clinicians with an efficacious option to treat patients with multiple sclerosis.
Topics: Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Immunologic Factors; Multiple Sclerosis, Chronic Progressive; Recurrence
PubMed: 36728340
DOI: 10.1002/acn3.51732 -
Journal of Neurology Jan 2021We conducted a systematic review and wide-angled Mendelian randomization (MR) study to examine the association between possible risk factors and multiple sclerosis (MS).
OBJECTIVES
We conducted a systematic review and wide-angled Mendelian randomization (MR) study to examine the association between possible risk factors and multiple sclerosis (MS).
METHODS
We used MR analysis to assess the associations between 65 possible risk factors and MS using data from a genome-wide association study including 14 498 cases and 24 091 controls of European ancestry. For 18 exposures not suitable for MR analysis, we conducted a systematic review to obtain the latest meta-analyses evidence on their associations with MS.
RESULTS
Childhood and adulthood body mass index were positively associated with MS, whereas physical activity and serum 25-hydroxyvitamin D were inversely associated with MS. There was evidence of possible associations of type 2 diabetes, waist circumference, body fat percentage, age of puberty and high-density lipoprotein cholesterol. Data of systematic review showed that exposure to organic solvents, Epstein Barr virus and cytomegalovirus virus infection, and diphtheria and tetanus vaccination were associated with MS risk.
CONCLUSIONS
This study identified several modifiable risk factors for primary prevention of MS that should inform public health policy.
Topics: Adult; Child; Diabetes Mellitus, Type 2; Epstein-Barr Virus Infections; Genome-Wide Association Study; Herpesvirus 4, Human; Humans; Mendelian Randomization Analysis; Multiple Sclerosis; Risk Factors
PubMed: 32728946
DOI: 10.1007/s00415-020-10119-8 -
BMC Neurology Dec 2021Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that results in progressive and irreversible disability. Fatigue is one of the...
BACKGROUND
Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that results in progressive and irreversible disability. Fatigue is one of the most common MS-related symptoms and is characterized by a persistent lack of energy that impairs daily functioning. The burden of MS-related fatigue is complex and multidimensional, and to our knowledge, no systematic literature review has been conducted on this subject. The purpose of this study was to conduct a systematic literature review on the epidemiology and burden of fatigue in people with multiple sclerosis (pwMS).
METHODS
Systematic searches were conducted in MEDLINE, Embase, and Evidence-Based Medicine Reviews to identify relevant studies of fatigue in pwMS. English-language records published from 2010 to January 2020 that met predefined eligibility criteria were included. We initially selected studies that reported quality of life (QoL) and economic outcomes according to categories of fatigue (e.g., fatigued vs non-fatigued). Studies assessing associations between economic outcomes and fatigue as a continuous measure were later included to supplement the available data.
RESULTS
The search identified 8147 unique records, 54 of which met the inclusion criteria. Of these, 39 reported epidemiological outcomes, 11 reported QoL, and 9 reported economic outcomes. The supplementary screen for economic studies with fatigue as a continuous measure included an additional 20 records. Fatigue prevalence in pwMS ranged from 36.5 to 78.0%. MS-related fatigue was consistently associated with significantly lower QoL. Results on the economic impact of fatigue were heterogeneous, but most studies reported a significant association between presence or severity of fatigue and employment status, capacity to work, and sick leave. There was a gap in evidence regarding the direct costs of MS-related fatigue and the burden experienced by caregivers of pwMS.
CONCLUSION
Fatigue is a prevalent symptom in pwMS and is associated with considerable QoL and economic burden. There are gaps in the evidence related to the direct costs of MS-related fatigue and the burden of fatigue on caregivers. Addressing fatigue over the clinical course of the disease may improve health and economic outcomes for patients with MS.
Topics: Fatigue; Humans; Multiple Sclerosis; Prevalence; Quality of Life
PubMed: 34856949
DOI: 10.1186/s12883-021-02396-1 -
Neurological Sciences : Official... Mar 2023Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS). The most common clinical manifestations of MS... (Review)
Review
OBJECTIVE
Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS). The most common clinical manifestations of MS are spasticity, pain, vesico-urethral disorders, cognitive impairments, chronic fatigue and sexual dysfunction. This review aims to explore the possible therapeutic options for managing sexual dysfunction in people with MS (PwMS).
METHOD
A thorough search of the PubMed Medline database was performed. Records were limited to clinical studies published between 01/01/2010 up to 01/01/2022. The results were screened by the authors in pairs.
RESULTS
The search identified 36 records. After screening, 9 records met the inclusion-exclusion criteria and were assessed. The pharmacological approaches investigated the effectiveness of sildenafil, tadalafil and onabotulinumtoxinA. Of the interventional studies the non-pharmacological investigated, the effectiveness of aquatic exercises, the application of pelvic floor exercises,the combination of pelvic floor exercises and mindfulness technique, the combination of pelvic floor exercises and electro muscular stimulation with electromyograph biofeedback, the application of yoga techniques and the efficacy of assistive devices like the clitoral vacuum suction device and the vibration device.
CONCLUSION
The management of sexual dysfunction in PwMS needs to be further investigated. A team of healthcare professionals should be involved in the management of SD in order to address not only the primary (MS-related) SD symptoms but the secondary and tertiary as well. The main limitations that were identified in the existing literature were related to MS disease features, sample characteristics and evaluation tools and batteries.
Topics: Humans; Multiple Sclerosis; Sexual Dysfunction, Physiological; Sildenafil Citrate; Pain; Exercise Therapy
PubMed: 36585597
DOI: 10.1007/s10072-022-06572-0 -
Multiple Sclerosis (Houndmills,... Feb 2023Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC) in cerebrospinal fluid.
OBJECTIVE
To perform a systematic review and meta-analysis to evaluate whether κ-FLC index has similar diagnostic value to identify patients with clinically isolated syndrome (CIS) or MS compared to OCB, and to determine κ-FLC index cut-off.
METHODS
PubMed was searched for studies that assessed diagnostic sensitivity and specificity of κ-FLC index and OCB to discriminate CIS/MS patients from control subjects. Two reviewers following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines performed study eligibility assessment and data extraction. Findings from studies were analyzed with bivariate mixed models.
RESULTS
A total of 32 studies were included in the meta-analysis to evaluate diagnostic value of κ-FLC index. Sensitivity and specificity ranged from 52% to 100% (weighted average: 88%) and 69% to 100% (89%) for κ-FLC index and from 37% to 100% (85%) and 74% to 100% (92%) for OCB. Mean difference of sensitivity and specificity between κ-FLC index and OCB was 2 and -4 percentage points. Diagnostic accuracy determined by mixed models revealed no significant difference between κ-FLC index and OCB. A discriminatory cut-off for κ-FLC index was determined at 6.1.
CONCLUSION
The findings indicate that κ-FLC index has similar diagnostic accuracy in MS as OCB.
Topics: Humans; Multiple Sclerosis; Immunoglobulin kappa-Chains; Oligoclonal Bands; Immunoglobulin G; Demyelinating Diseases; Biomarkers
PubMed: 36453167
DOI: 10.1177/13524585221134213 -
Neurologia 2020Numerous cases have been reported of patients with symptoms of Guillain-Barré syndrome associated with COVID-19, but much information is still lacking on this...
INTRODUCTION
Numerous cases have been reported of patients with symptoms of Guillain-Barré syndrome associated with COVID-19, but much information is still lacking on this association and its implications. The objective of this review is to analyse the available evidence on this topic in the adult population.
MATERIAL AND METHODS
A systematic review was conducted of studies published on scientific databases: PubMed, Cochrane, Science Direct, Medline, and WHO COVID-19 database.
RESULTS
We identified 47 studies, which were analysed and completed using the Covidence platform; the final analysis included 24 articles, with a total of 30 patients.
CONCLUSIONS
We found a strong association between both conditions; furthermore, the studies analysed highlight differences in the presentation of the disease, with greater severity of symptoms in Guillain-Barre syndrome associated with COVID-19.
Topics: Adult; Aged; Betacoronavirus; COVID-19; Causality; Coronavirus Infections; Female; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32896460
DOI: 10.1016/j.nrl.2020.07.004 -
Expert Review of Neurotherapeutics Apr 2021Individuals with Guillain-Barrè syndrome (GBS) showed significant longer-term psychological sequelae, due to persistent disability. In recent years, great advances have...
INTRODUCTION
Individuals with Guillain-Barrè syndrome (GBS) showed significant longer-term psychological sequelae, due to persistent disability. In recent years, great advances have been made in medical care for patients with GBS. However, the focus has been mainly on patient care in the acute phase and improving survival instead of long-term disability. The purpose of this study was to evaluate the efficacy of rehabilitation in people with GBS through a systematic review of randomized controlled trials.
AREA COVERED
PRISMA guidelines were used to perform this systematic review. Six bibliographic databases were searched: PUBMED, WEB OF SCIENCE, PEDro, CINHAL, PSYCHINFO, and SCOPUS. Papers included in the systematic review should have a search design of a randomized controlled trial. The quality of the clinical trials included was evaluated according to Jadad score.
EXPERT OPINION
After eliminating duplicates, 472 records got screened, three RCTs were included in the systematic review. Overall, the analysis of the three randomized controlled trials showed that various types of rehabilitation interventions are correlated to an improvement in the patient's well-being. Finally, it is not possible to extrapolate definite conclusions on the effectiveness of rehabilitation treatment in patients with GBS. Therefore, high-quality future studies are needed to confirm these hypotheses.
Topics: Guillain-Barre Syndrome; Humans; Randomized Controlled Trials as Topic
PubMed: 33567916
DOI: 10.1080/14737175.2021.1890034 -
Autoimmunity Reviews Mar 2022Corticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin (IVIg) and plasmapheresis, have shown mixed results in patient improvement.
OBJECTIVE
To compare the efficacy of IVIg administration with that of corticosteroids, plasmapheresis, and placebo in autoimmune neurological diseases like Guillain-Barré syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, optic neuritis, and multiple sclerosis.
METHODS
A systematic review was performed on the databases PubMed, MEDLINE, Embase, and Cochrane. Controlled, randomized studies comparing the efficacy of IVIg with placebo, plasmapheresis, and/or glucocorticoid administration were selected. Only studies reporting the number of patients who improved after treatment were included, irrespective of language or publication year. In total, 23 reports were included in the meta-analysis study.
RESULTS
Our meta-analysis showed a beneficial effect of IVIg administration on patient improvement over placebo (OR = 2.79, CI [95%] = 1.40-5.55, P = 0.01). Meanwhile, IVIg administration showed virtually identical effects to plasmapheresis (OR = 0.83, CI [95%] = 0.45-1.55, P < 0.01). Finally, no significant differences were found in the efficacy of IVIg and glucocorticoid administration (OR = 0.98, Cl [95%] = 0.58-1.68, P = 0.13).
CONCLUSION
IVIg can be regarded as a viable therapeutic approach, either as a first- or second-line therapy, and as an adjuvant therapy for autoimmune neurological diseases.
Topics: Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Myasthenia Gravis; Plasma Exchange; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
PubMed: 34920107
DOI: 10.1016/j.autrev.2021.103019 -
JAMA Neurology Nov 2023Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in...
IMPORTANCE
Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (RRMS). To date, there is no uniform agreed-upon definition of PIRA, limiting the comparability of published studies.
OBJECTIVE
To summarize the current evidence about PIRA based on a systematic review, to discuss the various terminologies used in the context of PIRA, and to propose a harmonized definition for PIRA for use in clinical practice and future trials.
EVIDENCE REVIEW
A literature search was conducted using the search terms multiple sclerosis, PIRA, progression independent of relapse activity, silent progression, and progression unrelated to relapses in PubMed, Embase, Cochrane, and Web of Science, published between January 1990 and December 2022.
FINDINGS
Of 119 identified single records, 48 eligible studies were analyzed. PIRA was reported to occur in roughly 5% of all patients with RRMS per annum, causing at least 50% of all disability accrual events in typical RRMS. The proportion of PIRA vs relapse-associated worsening increased with age, longer disease duration, and, despite lower absolute event numbers, potent suppression of relapses by highly effective disease-modifying therapy. However, different studies used various definitions of PIRA, rendering the comparability of studies difficult.
CONCLUSION AND RELEVANCE
PIRA is the most frequent manifestation of disability accumulation across the full spectrum of traditional MS phenotypes, including clinically isolated syndrome and early RRMS. The harmonized definition suggested here may improve the comparability of results in current and future cohorts and data sets.
Topics: Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Chronic Disease; Recurrence; PubMed; Disease Progression
PubMed: 37782515
DOI: 10.1001/jamaneurol.2023.3331 -
The Cochrane Database of Systematic... Jan 2017Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory... (Review)
Review
BACKGROUND
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affects about 2 to 3 per 100,000 of the population. More than half of affected people cannot walk unaided when symptoms are at their worst. CIDP usually responds to treatments that reduce inflammation, but there is disagreement about which treatment is most effective.
OBJECTIVES
To summarise the evidence from Cochrane systematic reviews (CSRs) and non-Cochrane systematic reviews of any treatment for CIDP and to compare the effects of treatments.
METHODS
We considered all systematic reviews of randomised controlled trials (RCTs) of any treatment for any form of CIDP. We reported their primary outcomes, giving priority to change in disability after 12 months.Two overview authors independently identified published systematic reviews for inclusion and collected data. We reported the quality of evidence using GRADE criteria. Two other review authors independently checked review selection, data extraction and quality assessments.On 31 October 2016, we searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (in theCochrane Library), MEDLINE, Embase, and CINAHL Plus for systematic reviews of CIDP. We supplemented the RCTs in the existing CSRs by searching on the same date for RCTs of any treatment of CIDP (including treatment of fatigue or pain in CIDP), in the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus.
MAIN RESULTS
Five CSRs met our inclusion criteria. We identified 23 randomised trials, of which 15 had been included in these CSRs. We were unable to compare treatments as originally planned, because outcomes and outcome intervals differed. CorticosteroidsIt is uncertain whether daily oral prednisone improved impairment compared to no treatment because the quality of the evidence was very low (1 trial, 28 participants). According to moderate-quality evidence (1 trial, 41 participants), six months' treatment with high-dose monthly oral dexamethasone did not improve disability more than daily oral prednisolone. Observational studies tell us that prolonged use of corticosteroids sometimes causes serious side-effects. Plasma exchangeAccording to moderate-quality evidence (2 trials, 59 participants), twice-weekly plasma exchange produced more short-term improvement in disability than sham exchange. In the largest observational study, 3.9% of plasma exchange procedures had complications. Intravenous immunoglobulinAccording to high-quality evidence (5 trials, 269 participants), intravenous immunoglobulin (IVIg) produced more short-term improvement than placebo. Adverse events were more common with IVIg than placebo (high-quality evidence), but serious adverse events were not (moderate-quality evidence, 3 trials, 315 participants). One trial with 19 participants provided moderate-quality evidence of little or no difference in short-term improvement of impairment with plasma exchange in comparison to IVIg. There was little or no difference in short-term improvement of disability with IVIg in comparison to oral prednisolone (moderate-quality evidence; 1 trial, 29 participants) or intravenous methylprednisolone (high-quality evidence; 1 trial, 45 participants). One unpublished randomised open trial with 35 participants found little or no difference in disability after three months of IVIg compared to oral prednisone; this trial has not yet been included in a CSR. We know from observational studies that serious adverse events related to IVIg do occur. Other immunomodulatory treatmentsIt is uncertain whether the addition of azathioprine (2 mg/kg) to prednisone improved impairment in comparison to prednisone alone, as the quality of the evidence is very low (1 trial, 27 participants). Observational studies show that adverse effects truncate treatment in 10% of people.According to low-quality evidence (1 trial, 60 participants), compared to placebo, methotrexate 15 mg/kg did not allow more participants to reduce corticosteroid or IVIg doses by 20%. Serious adverse events were no more common with methotrexate than with placebo, but observational studies show that methotrexate can cause teratogenicity, abnormal liver function, and pulmonary fibrosis.According to moderate-quality evidence (2 trials, 77 participants), interferon beta-1a (IFN beta-1a) in comparison to placebo, did not allow more people to withdraw from IVIg. According to moderate-quality evidence, serious adverse events were no more common with IFN beta-1a than with placebo.We know of no other completed trials of immunosuppressant or immunomodulatory agents for CIDP. Other treatmentsWe identified no trials of treatments for fatigue or pain in CIDP. Adverse effectsNot all trials routinely collected adverse event data; when they did, the quality of evidence was variable. Adverse effects in the short, medium, and long term occur with all interventions. We are not able to make reliable comparisons of adverse events between the interventions included in CSRs.
AUTHORS' CONCLUSIONS
We cannot be certain based on available evidence whether daily oral prednisone improves impairment compared to no treatment. However, corticosteroids are commonly used, based on widespread availability, low cost, very low-quality evidence from observational studies, and clinical experience. The weakness of the evidence does not necessarily mean that corticosteroids are ineffective. High-dose monthly oral dexamethasone for six months is probably no more or less effective than daily oral prednisolone. Plasma exchange produces short-term improvement in impairment as determined by neurological examination, and probably produces short-term improvement in disability. IVIg produces more short-term improvement in disability than placebo and more adverse events, although serious side effects are probably no more common than with placebo. There is no clear difference in short-term improvement in impairment with IVIg when compared with intravenous methylprednisolone and probably no improvement when compared with either oral prednisolone or plasma exchange. According to observational studies, adverse events related to difficult venous access, use of citrate, and haemodynamic changes occur in 3% to17% of plasma exchange procedures.It is uncertain whether azathioprine is of benefit as the quality of evidence is very low. Methotrexate may not be of benefit and IFN beta-1a is probably not of benefit.We need further research to identify predictors of response to different treatments and to compare their long-term benefits, safety and cost-effectiveness. There is a need for more randomised trials of immunosuppressive and immunomodulatory agents, routes of administration, and treatments for symptoms of CIDP.
Topics: Adrenal Cortex Hormones; Azathioprine; Dexamethasone; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Interferon beta-1a; Methotrexate; Methylprednisolone; Plasma Exchange; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Prednisone; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 28084646
DOI: 10.1002/14651858.CD010369.pub2