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Cells Jun 2023Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been... (Review)
Review
Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been attributed to the propagation of inflammation and neurodegeneration in MS, mainly genetic, immunological, and environmental factors such as vitamin D deficiency, infections, or hormonal disbalance. Recently, the importance of the gut-brain axis for the development of many neurological conditions, including stroke, movement disorders, and neuroinflammatory disorders, has been postulated. The purpose of our paper was to summarize current evidence confirming the role of the gut microbiome in the pathophysiology of MS and related disorders, such as neuromyelitis optica spectrum disorder (NMO-SD). For this aim, we conducted a systematic review of the literature listed in the following databases: Medline, Pubmed, and Scopus, and were able to identify several studies demonstrating the involvement of the gut microbiome in the pathophysiology of MS and NMO-SD. It seems that the most relevant bacteria for the pathophysiology of MS are those belonging to , , , , , , , and , while and have been demonstrated to play a role in the pathophysiology of NMO-SD. Following this line of evidence, there is also some preliminary data supporting the use of probiotics or other agents affecting the microbiome that could potentially have a beneficial effect on MS/NMO-SD symptoms and prognosis. The topic of the gut microbiome in the pathophysiology of MS is therefore relevant since it could be used as a biomarker of disease development and progression as well as a potential disease-modifying therapy.
Topics: Humans; Multiple Sclerosis; Gastrointestinal Microbiome; Neuromyelitis Optica; Vitamin D Deficiency; Inflammation
PubMed: 37443793
DOI: 10.3390/cells12131760 -
The Cochrane Database of Systematic... Nov 2021Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, with an unpredictable course. Current MS therapies such as disease-modifying... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, with an unpredictable course. Current MS therapies such as disease-modifying therapies focus on treating exacerbations, preventing new exacerbations and avoiding the progression of disability. Siponimod (BAF312) is an oral treatment, a selective sphingosine-1-phosphate (S1P) receptor modulator, for the treatment of adults with relapsing forms of MS including active, secondary progressive MS with relapses.
OBJECTIVES
To assess the benefits and adverse effects of siponimod as monotherapy or combination therapy versus placebo or any active comparator for people diagnosed with MS.
SEARCH METHODS
On 18 June 2020, we searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Trials Register, which contains studies from CENTRAL, MEDLINE and Embase, and the trials registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP). We also handsearched relevant journals and screened the reference lists of published reviews and retrieved articles and searched reports (2004 to June 2020) from the MS societies in Europe and America.
SELECTION CRITERIA
We included randomised parallel controlled clinical trials (RCTs) that evaluated siponimod, as monotherapy or combination therapy, versus placebo or any active comparator in people with MS. There were no restrictions on dose or administration frequency.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We discussed disagreements and resolved them by consensus among the review authors. Our primary outcomes wereworsening disability , relapse and adverse events, and secondary outcomes were annualised relapse rate, gadolinium-enhancing lesions, new lesions or enlarged pre-existing lesions and mean change of brain volume. We independently evaluated the certainty of evidence using the GRADE approach. We contacted principal investigators of included studies for additional data or confirmation of data.
MAIN RESULTS
Two studies (1948 participants) met our selection criteria, 608 controls and 1334 treated with siponimod. The included studies compared siponimod with placebo. Overall, all studies had a high risk of bias due to selective reporting and attrition bias. Comparing siponimod administered at a dose of 2 mg to placebo, we found that siponimod may reduce the number of participants with disability progression at six months (56 fewer people per 1000; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.65 to 0.94; 1 study, 1641 participants; low-certainty evidence) and annualised relapse rate (RR 0.43, 95% CI 0.34 to 0.56; 2 studies, 1739 participants; low-certainty evidence). But it might lead to little reduction in the number of participants with new relapse (166 fewer people per 1000; RR 0.38, 95% CI 0.15 to 1.00; 1 study, 94 participants; very low-certainty evidence). We observed no evidence of a difference due to adverse events for siponimod at 2 mg compared to placebo (14 more people per 1000; RR 1.52, 95% CI 0.85 to 2.71; 2 studies, 1739 participants, low-certainty evidence). In addition, due to the high risk of inaccurate magnetic resonance imaging (MRI) data in the two included studies, we could not combine data for active lesions on MRI scans. Both studies had high attrition bias resulting from the unbalanced reasons for dropouts among groups and high risk of bias due to conflicts of interest. Siponimod may reduce the number of gadolinium-enhancing T1-weighted lesions at two years of follow-up (RR 0.14, 95% CI 0.10 to 0.19; P < 0.0001; 1 study, 1641 participants; very low-certainty evidence). There may be no evidence of a difference between groups in the number of participants with at least one serious adverse event excluding relapses (113 more people per 1000; RR 1.80, 95% CI 0.37 to 8.77; 2 studies, 1739 participants; low-certainty evidence) at six months. No data were available regarding cardiac adverse events. In terms of safety profile, the most common adverse events associated with siponimod were headache, back pain, bradycardia, dizziness, fatigue, influenza, urinary tract infection, lymphopenia, nausea, alanine amino transferase increase and upper respiratory tract infection. These adverse events have dose-related effects and rarely led to discontinuation of treatment.
AUTHORS' CONCLUSIONS
Based on the findings of the RCTs included in this review, we are uncertain whether siponimod interventions are beneficial for people with MS. There was low-certainty evidence to support that siponimod at a dose of 2 mg orally once daily as monotherapy compared with placebo may reduce the annualised relapse rate and the number of participants who experienced disability worsening, at 6 months. However, the certainty of the evidence to support the benefit in reducing the number of people with a relapse is very low. The risk of withdrawals due to adverse events requires careful monitoring of participants over time. The duration of all studies was less than 24 months, so the efficacy and safety of siponimod over 24 months are still uncertain, and further exploration is needed in the future. There is no high-certainty data available to evaluate the benefit on MRI outcomes. We assessed the certainty of the body of evidence for all outcomes was low to very low, downgraded due to serious study limitations, imprecision and indirectness. We are uncertain whether siponimod is beneficial for people with MS. More new studies with robust methodology and longer follow-up are needed to evaluate the benefit of siponimod for the management of MS and to observe long-term adverse effects. Also, in addition to comparing with placebo, more new studies are needed to evaluate siponimod versus other therapeutic options.
Topics: Adult; Azetidines; Benzyl Compounds; Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive
PubMed: 34783010
DOI: 10.1002/14651858.CD013647.pub2 -
Nutrients Jun 2023Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS).... (Meta-Analysis)
Meta-Analysis Review
Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS). However, its effect on disease symptoms remains unclear. The aim of this meta-analysis was to conduct a systematic review to assess the effect of vitamin D on fatigue in this population. The systematic review was conducted using the MEDLINE, Cochrane Library, Embase and Web of Science databases from inception to May 2023. Randomized controlled trials (RCTs) reporting pre-post changes in fatigue after vitamin D supplementation were included. Pooled effect sizes and 95% confidence intervals (95% CIs) were calculated by applying a random effects model with Stata/SE (Version 16.0; StataCorp., College Station, TX, USA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of five studies with 345 individuals (271 females; age range: 25.4-41.1 years) were included. A significant reduction in fatigue was perceived when vitamin D supplementation was compared with a control group: -0.18 (95% CI: -0.36 to -0.01; I = 0%). Thus, our findings show that the therapeutic use of vitamin D on fatigue in people with MS could be considered. Nevertheless, due to the lack of agreement on the dose to be applied, it is recommended to use it under medical prescription.
Topics: Adult; Female; Humans; Dietary Supplements; Fatigue; Multiple Sclerosis; Vitamin D; Male
PubMed: 37447189
DOI: 10.3390/nu15132861 -
The Cochrane Database of Systematic... Feb 2014This is an update of the Cochrane review 'Neuropsychological rehabilitation for multiple sclerosis' (first published in The Cochrane Library 2011, Issue 11).Cognitive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the Cochrane review 'Neuropsychological rehabilitation for multiple sclerosis' (first published in The Cochrane Library 2011, Issue 11).Cognitive deficits are a common manifestation of multiple sclerosis (MS) and have a significant effect on the patient's quality of life. Alleviation of the harmful effects caused by these deficits should be a major goal of MS research and practice.
OBJECTIVES
To assess the effects of neuropsychological/cognitive rehabilitation on health-related factors, such as cognitive performance and emotional well-being in patients with MS.
SEARCH METHODS
The Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Search Co-ordinator searched their Specialised Register which, among other sources, contains trials from CENTRAL (The Cochrane Library 2013, Issue 2), MEDLINE, EMBASE, CINAHL, LILACS, PEDro and clinical trials registries (28 May 2013). We contacted authors of the studies for additional information.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-randomised trials evaluating the effects of neuropsychological rehabilitation in MS compared to other interventions or no intervention.
DATA COLLECTION AND ANALYSIS
Two review authors individually judged the eligibility of the included studies, assessed risk of bias and extracted data. We combined results quantitatively in meta-analyses according to the intervention type: 1) cognitive training and 2) cognitive training combined with other neuropsychological rehabilitation methods.
MAIN RESULTS
Twenty studies (986 participants; 966 MS participants and 20 healthy controls) fulfilled the inclusion criteria. The mean age of the participants was 44.6 years, mean length of education was 12.3 years and 70% of the participants were women. Most of the participants had a relapsing-remitting course of disease. The mean Expanded Disability Status Scale score was 3.2 and the mean duration of disease was 14.0 years.On the basis of these studies, we found low-level evidence that neuropsychological rehabilitation reduces cognitive symptoms in MS. Cognitive training was found to improve memory span (standardised mean difference (SMD) 0.54, 95% confidence interval (CI) 0.20 to 0.88, P = 0.002) and working memory (SMD 0.33, 95% CI 0.09 to 0.57, P = 0.006). Cognitive training combined with other neuropsychological rehabilitation methods was found to improve attention (SMD 0.15, 95% CI 0.01 to 0.28, P = 0.03), immediate verbal memory (SMD 0.31, 95% CI 0.08 to 0.54, P = 0.008) and delayed memory (SMD 0.22, 95% CI 0.02 to 0.42, P = 0.03). There was no evidence of an effect of neuropsychological rehabilitation on emotional functions.The overall quality, as well as the comparability of the included studies, was relatively low due to methodological limitations and heterogeneity of interventions and outcome measures. Although most of the pooled results in the meta-analyses yielded no significant findings, 18 of the 20 studies showed some evidence of positive effects when the studies were individually analysed.
AUTHORS' CONCLUSIONS
This review found low-level evidence for positive effects of neuropsychological rehabilitation in MS. The interventions and outcome measures included in the review were heterogeneous, which limited the comparability of the studies. New trials may therefore change the strength and direction of the evidence.
Topics: Adult; Cognition Disorders; Depression; Female; Humans; Male; Memory Disorders; Multiple Sclerosis; Neuropsychology; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 24515630
DOI: 10.1002/14651858.CD009131.pub3 -
Reviews in the Neurosciences Aug 2021Multiple sclerosis (MS) is a neurodegenerative disease associated with inflammatory demyelination and astroglial activation, with neuronal and axonal damage as the... (Meta-Analysis)
Meta-Analysis
Multiple sclerosis (MS) is a neurodegenerative disease associated with inflammatory demyelination and astroglial activation, with neuronal and axonal damage as the leading factors of disability. We aimed to perform a meta-analysis to determine changes in CSF levels of neuronal and glial biomarkers, including neurofilament light chain (NFL), total tau (t-tau), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), and S100B in various groups of MS (MS versus controls, clinically isolated syndrome (CIS) versus controls, CIS versus MS, relapsing-remitting MS (RRMS) versus progressive MS (PMS), and MS in relapse versus remission. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 64 articles in the meta-analysis, including 4071 subjects. For investigation of sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. Meta-analyses were performed for comparisons including at least three individual datasets. NFL, GFAP, t-tau, CHI3L1, and S100B were higher in MS and NFL, t-tau, and CHI3L1 were also elevated in CIS patients than controls. CHI3L1 was the only marker with higher levels in MS than CIS. GFAP levels were higher in PMS versus RRMS, and NFL, t-tau, and CHI3L1 did not differ between different subtypes. Only levels of NFL were higher in patients in relapse than remission. Meta-regression showed influence of sex and disease severity on NFL and t-tau levels, respectively and disease duration on both. Added to the role of these biomarkers in determining prognosis and treatment response, to conclude, they may serve in diagnosis of MS and distinguishing different subtypes.
Topics: Biomarkers; Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Neurodegenerative Diseases; Neuroglia
PubMed: 33594840
DOI: 10.1515/revneuro-2020-0145 -
PloS One 2013A role for Epstein Barr virus (EBV) in multiple sclerosis (MS) has been postulated. Previous systematic reviews found higher prevalences of anti-EBV antibodies in MS... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A role for Epstein Barr virus (EBV) in multiple sclerosis (MS) has been postulated. Previous systematic reviews found higher prevalences of anti-EBV antibodies in MS patients compared to controls, but many studies have since been published, and there is a need to apply more rigorous systematic review methods.
METHODOLOGY/PRINCIPAL FINDINGS
We examined the link between EBV and MS by conducting a systematic review and meta-analysis of case-control and cohort studies that examined the prevalence of anti-EBV antibodies in the serum of cases and controls. We searched Medline and Embase databases from 1960 to 2012, with no language restriction. The Mantel-Haenszel odds ratios (OR) for anti-EBV antibodies sero-positivity were calculated, and meta-analysis conducted. Quality assessment was performed using a modified version of the Newcastle Ottawa scale. Thirty-nine studies were included. Quality assessment found most studies reported acceptable selection and comparability of cases and controls. However the majority had poor reporting of ascertainment of exposure. Most studies found a higher sero-prevalence of anti-EBNA IgG and anti-VCA IgG in cases compared to controls. The results for anti-EA IgG were mixed with only half the studies finding a higher sero-prevalence in cases. The meta-analysis showed a significant OR for sero-positivity to anti-EBNA IgG and anti-VCA IgG in MS cases (4.5 [95% confidence interval (CI) 3.3 to 6.6, p<0.00001] and 4.5 [95% CI 2.8 to 7.2, p<0.00001] respectively). However, funnel plot examination suggested publication bias for the reporting of the anti-EBNA IgG. No significant difference in the OR for sero-positivity to anti-EA IgG was found (1.4 [95% CI 0.9 to 2.1, p = 0.09]).
CONCLUSION/SIGNIFICANCE
These findings support previous systematic reviews, however publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly with regard to reporting and conduct of laboratory analyses.
Topics: Adolescent; Adult; Antibodies, Viral; Child; Child, Preschool; Databases, Bibliographic; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; Female; Herpesvirus 4, Human; Humans; Immunoglobulin G; Male; Multiple Sclerosis; Odds Ratio; Publication Bias
PubMed: 23585874
DOI: 10.1371/journal.pone.0061110 -
Nutrients Apr 2023The link between vitamin D and multiple sclerosis (MS) has been suggested in epidemiological, genetic, immunological, and clinical studies. The aim of the present... (Review)
Review
The link between vitamin D and multiple sclerosis (MS) has been suggested in epidemiological, genetic, immunological, and clinical studies. The aim of the present systematic review of the literature was to assess the effects of vitamin D supplementation on clinical and imaging outcomes in patients with MS. The outcomes we assessed included relapse events, disability progression, and magnetic resonance imaging (MRI) lesions. The search was conducted using PubMed, ClinicalTrials.gov, and EudraCT databases, and it included records published up until 28 February 2023. The systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Nineteen independent clinical studies (corresponding to 24 records) were included in the systematic review. The risk of bias in randomized controlled trials (RCTs) was analyzed using the Cochrane risk-of-bias tool. Fifteen trials investigated relapse events, and most of them reported no significant effect of vitamin D supplementation. Eight of 13 RCTs found that vitamin D supplementation had no effect on disability [assessed by Expanded Disability Status Scale (EDSS) scores] compared to controls. Interestingly, recent RCTs reported a significant reduction in new MRI lesions in the central nervous system of MS patients during supplementation with vitamin D3.
Topics: Humans; Vitamins; Vitamin D; Multiple Sclerosis; Dietary Supplements; Recurrence
PubMed: 37111166
DOI: 10.3390/nu15081945 -
The Cochrane Database of Systematic... Apr 2016Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS therapies focus on treating exacerbations, preventing new exacerbations and avoiding the progression of disability. However, at present there is no effective treatment that is capable of safely and effectively reaching these objectives. This has led to the development and investigation of new drugs. Recent clinical trials suggest that alemtuzumab, a humanised monoclonal antibody against cell surface CD52, could be a promising option for MS.
OBJECTIVES
To assess the safety and effectiveness of alemtuzumab used alone or associated with other treatments to decrease disease activity in patients with any form of MS.
SEARCH METHODS
We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group (30 April 2015), which contains trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS and the trial registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform. There was no restriction on the source, publication date or language.
SELECTION CRITERIA
All randomised clinical trials (RCTs) involving adults diagnosed with any form of MS according to the McDonald criteria, comparing alemtuzumab alone or associated with other medications, at any dose and for any duration, versus placebo or any other active drug therapy or alemtuzumab in other dose, regimen or duration. The co-primary outcomes were relapse-free survival, sustained disease progression and number of participants with at least one of any adverse events, including serious adverse events.
DATA COLLECTION AND ANALYSIS
Two independent review authors performed study selection, data extraction and 'Risk of bias' assessment. A third review author checked the process for accuracy. We used the Cochrane 'Risk of bias' tool to assess the risk of bias of the studies included in the review. We used the GRADE system to assess the quality of the body of evidence. To measure the treatment effect on dichotomous outcomes we used the risk ratio (RR); for the treatment effect on continuous outcomes, we used the mean difference (MD) and for time-to-event outcomes we used hazard ratio (HR). We calculated 95% confidence intervals (CI) for these measures. When there was no heterogeneity, we used a fixed-effect model to pool data.
MAIN RESULTS
Three RCTs (1713 participants) fulfilled the selection criteria and we included them in the review. All three trials compared alemtuzumab versus subcutaneous interferon beta-1a for patients with relapsing-remitting MS. Patients were treatment-naive in the CARE-MS and CAMMS223 studies. The CARE-MS II study included patients with at least one relapse while being treated with interferon beta or glatiramer acetate. Alemtuzumab was given for 12 or 24 months; for some outcomes, the follow-up period reached 36 months. The regimens were (a) 12 mg or 24 mg per day administered intravenously, once a day for five consecutive days at month 0 and 12 or (b) 24 mg per day, intravenously, once a day for three consecutive days at month 12 and 24. The patients in the other arm of the trials received interferon beta-1a 44 μg subcutaneously three times weekly after dose titration.At 24 months, alemtuzumab 12 mg was associated with: (a) higher relapse-free survival (hazard ratio (HR) 0.50, 95% CI 0.41 to 0.60; 1248 participants, two studies, moderate quality evidence); (b) higher sustained disease progression-free survival (HR 0.62, 95% CI 0.44 to 0.87; 1191 participants; two studies; moderate quality evidence); (c) a slightly higher number of participants with at least one adverse event (RR 1.04, 95% CI 1.01 to 1.06; 1248 participants; two studies; moderate quality evidence); (d) a lower number of participants with new or enlarging T2-hyperintense lesions on magnetic resonance imaging (MRI) (RR 0.74, 95% CI 0.59 to 0.91; 1238 participants; two studies; I(2) = 80%); and (e) a lower number of dropouts (RR 0.31, 95% CI 0.23 to 0.41; 1248 participants; two studies, I(2) = 29%; low quality evidence).At 36 months, alemtuzumab 24 mg was associated with: (a) higher relapse-free survival (45 versus 17; HR 0.21, 95% CI 0.11 to 0.40; one study; 221 participants); (b) a higher sustained disease progression-free survival (HR 0.33, 95% CI 0.16 to 0.69; one study; 221 participants); and (c) no statistical difference in the rate of participants with at least one adverse event. We did not find any study that reported any of the following outcomes: rate of participants free of clinical disease activity, quality of life, fatigue or change in the numbers of MRI T2- and T1-weighted lesions after treatment. It was not possible to perform subgroup analyses according to disease type and disability at baseline due to lack of data.
AUTHORS' CONCLUSIONS
In patients with relapsing-remitting MS, alemtuzumab 12 mg was better than subcutaneous interferon beta-1a for the following outcomes assessed at 24 months: relapse-free survival, sustained disease progression-free survival, number of participants with at least one adverse event and number of participants with new or enlarging T2-hyperintense lesions on MRI. The quality of the evidence for these results was low to moderate. Alemtuzumab 24 mg seemed to be better than subcutaneous interferon beta-1a for relapse-free survival and sustained disease progression-free survival, at 36 months.More randomised clinical trials are needed to evaluate the effects of alemtuzumab on other forms of MS and compared with other therapeutic options. These new studies should assess additional relevant outcomes such as the rate of participants free of clinical disease activity, quality of life, fatigue and adverse events (individual rates, serious adverse events and long-term adverse events). Moreover, these new studies should evaluate other doses and durations of alemtuzumab course.
Topics: Adult; Alemtuzumab; Antibodies, Monoclonal, Humanized; Disease-Free Survival; Humans; Interferon beta-1a; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 27082500
DOI: 10.1002/14651858.CD011203.pub2 -
Neurological Sciences : Official... May 2023To exp lore changes in immunoglobulin (Ig) levels for people with relapsing-multiple sclerosis (RMS) treated with ocrelizumab or ofatumumab and the relationship between... (Review)
Review
OBJECTIVE
To exp lore changes in immunoglobulin (Ig) levels for people with relapsing-multiple sclerosis (RMS) treated with ocrelizumab or ofatumumab and the relationship between Ig levels and infections.
METHODS
A systematic literature review (SLR) was conducted to identify clinical trials and real-world evidence (RWE) studies on Ig levels over time and studies on associations with infections for ocrelizumab and ofatumumab for people with RMS through 10 September 2021. Searches were conducted in Embase, MEDLINE, Cochrane Library, trial registries, and recent conference abstracts.
RESULTS
Of 1,580 articles identified, 30 reporting on 11 trials and 5 RWE studies were included. Ocrelizumab trials (n = 4) had 24-336 weeks of follow-up and reported decreasing Ig G (IgG) levels, while RWE (n = 5) had 52-78 weeks of follow-up and reported IgG to be stable or decrease only slightly. IgG levels were stable in ofatumumab trials (n = 5; 104-168 weeks of follow-up), but no RWE or longer-term studies were identified. No apparent association between decreased Ig levels and infections was observed during ofatumumab treatment (ASCLEPIOS I/II), while for ocrelizumab, the only data on apparent associations between decreased IgG levels and serious infection rates were for a pooled population of people with RMS or primary progressive MS.
CONCLUSION
Decreasing IgG levels have been correlated with increased infection risk over time. IgG levels appeared to decrease over time in ocrelizumab trials but remained relatively stable over time in ofatumumab trials. Additional research is needed to understand differences between ocrelizumab and ofatumumab and identify people at risk of decreasing IgG levels and infection.
Topics: Humans; Multiple Sclerosis; Antibodies, Monoclonal; Antineoplastic Agents; Immunoglobulin G; Multiple Sclerosis, Relapsing-Remitting
PubMed: 36648561
DOI: 10.1007/s10072-022-06582-y -
PloS One 2017The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS.
OBJECTIVE
To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients.
METHODS
Medline, Embase and the Cochrane Library were searched for published studies on the association of HERVs and MS. Meta-analysis was performed on the HERV-W family. Odds Ratio (OR) and 95% confidence interval (CI) were calculated for association.
RESULTS
43 reports were extracted (25 related to HERV-W, 13 to HERV-H, 9 to HERV-K, 5 to HRES-1 and 1 to HER-15 family). The analysis showed an association between expression of all HERV families and MS. For HERV-W, adequate data was available for meta-analysis. Results from meta-analyses of HERV-W were OR = 22.66 (95%CI 6.32 to 81.20) from 4 studies investigating MSRV/HERV-W (MS-associated retrovirus) envelope mRNA in peripheral blood mononuclear cells, OR = 44.11 (95%CI 12.95 to 150.30) from 6 studies of MSRV/HERV-W polymerase mRNA in serum/plasma and OR = 6.00 (95%CI 3.35 to 10.74) from 4 studies of MSRV/HERV-W polymerase mRNA in CSF.
CONCLUSIONS
This systematic review and meta-analysis shows an association between expression of HERVs, and in particular the HERV-W family, and MS.
Topics: Endogenous Retroviruses; Humans; Multiple Sclerosis
PubMed: 28207850
DOI: 10.1371/journal.pone.0172415