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Neurology India 2021Multiple sclerosis is a chronic demyelinating disorder with a myriad of imaging and clinical features that overlap with number of other neurological conditions.... (Review)
Review
BACKGROUND
Multiple sclerosis is a chronic demyelinating disorder with a myriad of imaging and clinical features that overlap with number of other neurological conditions. Incorrect diagnosis poses a significant risk to patients, it may lead to delays in management, increased morbidity, and also adds to the financial cost.
OBJECTIVE
The aim of this study was to highlight strategies for the efficient differentiation of multiple sclerosis from other diseases which may masquerade as MS clinico-radiologically.
MATERIAL AND METHODS
A systematic literature review was conducted through online databases including PubMed and Medline. Relevant publications on radiological aspects of multiple sclerosis, white matter diseases and mimickers of Multiple sclerosis were included in the analysis.
RESULTS
Common mimickers of MS include small vessel disease, acute disseminated encephalomyelitis, neuromyelitis optica, anti-MOG encephalomyelitis, vasculitis, and CADASIL. Contrast-enhanced MRI study performed using MS protocol on high strength MRI system evaluated following a structured protocol along with clinical correlation is effective in differentiating MS from its mimickers.
CONCLUSIONS
Contrast-enhanced MRI performed on a high strength scanner using MS protocol with structured protocol for evaluation along, with a better collaboration between radiologists and clinicians may help in minimizing errors in diagnosis of multiple sclerosis.
Topics: Encephalomyelitis; Encephalomyelitis, Acute Disseminated; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Neuromyelitis Optica
PubMed: 34979638
DOI: 10.4103/0028-3886.333497 -
Neurological Sciences : Official... Sep 2023Previously, several studies investigated the effect of cladribine among patients with multiple sclerosis (MS) as a treatment option. Due to the contradictory results of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previously, several studies investigated the effect of cladribine among patients with multiple sclerosis (MS) as a treatment option. Due to the contradictory results of previous studies regarding the efficacy and safety of cladribine in the MS population, we aimed to conduct a systematic review and meta-analysis by including clinical trials and observational studies in terms of having more confirmative results to make a general decision.
METHODS
The three databases including PubMed, Scopus, and Web of Science were comprehensively searched in May 2022. We included the studies that investigated the efficacy and safety of cladribine in patients with MS. Eligible studies have to provide sufficient details on MS diagnosis and appropriate follow-up duration. We investigated the efficacy of cladribine with several outcomes including Expanded Disability Status Scale (EDSS) change, progression-free survival (PFS), relapse-free survival (RFS), and MRI-free activity survival (MFAS).
RESULTS
After two-step reviewing, 23 studies were included in our qualitative and quantitative synthesis. The pooled SMD for EDSS before and after treatment was - 0.54 (95%CI: - 1.46, 0.39). Our analysis showed that the PFS after cladribine use is 79% (95%CI 71%, 86%). Also, 58% of patients with MS who received cladribine remained relapse-free (95%CI 31%, 83%). Furthermore, the MFAS after treatment was 60% (95%CI 36%, 81%). Our analysis showed that infection is the most common adverse event after cladribine treatment with a pooled prevalence of 10% (95%CI 4%, 18%). Moreover, the pooled prevalence of infusion-related adverse events was 9% (95%CI 4%, 15%). Also, the malignancies after cladribine were present in 0.4% of patients (95%CI 0.25%, 0.75%).
CONCLUSION
Our results showed acceptable safety and efficacy for cladribine for the treatment of MS except in terms of reducing EDSS. Combination of our findings with the results of previous studies which compared cladribine to other disease-modifying therapies (DMTs), cladribine seems to be a safe and effective drug in achieving better treatment for relapsing-remitting MS (RRMS) patients.
Topics: Humans; Cladribine; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Clinical Trials as Topic; Observational Studies as Topic
PubMed: 37062787
DOI: 10.1007/s10072-023-06794-w -
Current Opinion in Psychiatry Mar 2021Over 70 million people worldwide, including those with neurodegenerative disease (NDD), have been diagnosed with coronavirus disease 2019 (COVID-19) to date. We review...
PURPOSE OF REVIEW
Over 70 million people worldwide, including those with neurodegenerative disease (NDD), have been diagnosed with coronavirus disease 2019 (COVID-19) to date. We review outcomes in patients with NDD and COVID-19 and discuss the hypothesis that due to putative commonalities of neuropathogenesis, COVID-19 may unmask or trigger NDD in vulnerable individuals.
RECENT FINDINGS
Based on a systematic review of published literature, patients with NDD, including dementia, Parkinson's disease, and multiple sclerosis (MS) make up a significant portion of hospitalized COVID-19 patients. Such patients are likely to present with altered mental status or worsening of their preexisting neurological symptoms. Patients with NDD and poor outcomes often have high-risk comorbid conditions, including advanced age, hypertension, diabetes, obesity, and heart/lung disease. Patients with dementia including Alzheimer's disease are at higher risk for hospitalization and death, whereas those with preexisting Parkinson's disease are not. MS patients have good outcomes and disease modifying therapies do not increase the risk for severe disease. Viral infections and attendant neuroinflammation have been associated with the pathogenesis of Alzheimer's disease, Parkinson's disease, and MS, suggesting that COVID-19 may have the potential to incite or accelerate neurodegeneration.
SUMMARY
Since patients with Alzheimer's disease are at higher risk for hospitalization and death in the setting of COVID-19, additional precautions and protective measures should be put in place to prevent infections and optimize management of comorbidities in this vulnerable population. Further studies are needed to determine whether COVID-19 may lead to an increased risk of developing NDD in susceptible individuals.
Topics: COVID-19; Dementia; Hospitalization; Humans; Multiple Sclerosis; Parkinson Disease; Prognosis; Risk Factors
PubMed: 33395100
DOI: 10.1097/YCO.0000000000000688 -
Annals of Clinical and Translational... Feb 2022Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are two autoimmune diseases that seriously affect patients' quality of life. Previous studies have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are two autoimmune diseases that seriously affect patients' quality of life. Previous studies have established an association between MS and IBD, including Crohn's disease (CD) and ulcerative colitis (UC), but the results were inconsistent. The aim of this study was to quantify the prevalences of and the association between MS and IBD.
METHODS
The PubMed, Web of Science, and Embase databases were searched through November 2020 for studies reporting data on MS among patients with IBD and vice versa. The main outcomes were the proportion of MS in patients with IBD and vice versa, as well as the association (risk ratio [RR]) of IBD in MS and that of MS in IBD.
RESULTS
Based on the analysis of 17 studies, the prevalence of MS in patients with IBD was 0.2% (95% CI 0.1-0.4%), while the prevalence of IBD in patients with MS was 0.6% (95% CI 0.4-0.9%). Patients with MS had a higher prevalence of IBD than controls (RR = 1.53, 95% CI 1.38-1.70, p < 0.00001). There was a similarly high risk of developing CD (RR 1.41, 95% CI 1.14-1.74, p = 0.001) or UC (RR 1.42, 95% CI 1.17-1.71, p = 0.0003) in patients with MS (p for subgroup differences: 0.97). Patients with IBD had a higher prevalence of MS than controls (RR = 1.91, 95% CI 1.06-3.45, p = 0.03).
CONCLUSIONS
Clinicians should be aware of the increased risk of IBD or MS comorbidity during the diagnostic process. Systematic diagnosis and management at an earlier stage are suggested.
Topics: Comorbidity; Humans; Inflammatory Bowel Diseases; Multiple Sclerosis
PubMed: 35092169
DOI: 10.1002/acn3.51495 -
Frontiers in Neurology 2022Viral infections are a proposed possible cause of inflammatory central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS), neuromyelitis...
BACKGROUND
Viral infections are a proposed possible cause of inflammatory central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). During the past 2 years, CNS demyelinating events associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, but causality is unclear.
OBJECTIVE
To investigate the relationship between CNS demyelinating disease development and exacerbation with antecedent and/or concurrent SARS-CoV-2 infection.
METHODS
A systematic literature review of all publications describing either a new diagnosis or relapse of CNS demyelinating diseases (MS, NMOSD, MOGAD) in association with SARS-CoV-2 infection was performed utilizing PRISMA guidelines. Descriptive statistics were used for data analysis, using a case analysis approach.
RESULTS
Sixty-seven articles met the inclusion criteria for the study. Most of the reported cases of NMOSD ( = 13, 72.2% of reported cases) and MOGAD ( = 27, 96.5% of reported cases) were of new disease onset, presenting with typical clinical and radiographic features of these conditions, respectively. In contrast, reported MS cases varied amongst newly diagnosed cases ( = 10, 10.5% of reported cases), relapses ( = 63, 66.4%) and pseudo-relapses ( = 22, 23.2%). The median duration between COVID-19 infection and demyelinating event onset was 11.5 days (range 0-90 days) in NMOSD, 6 days (range-7 to +45 days) in MOGAD, and 13.5 days (range-21 to +180 days) in MS. Most cases received high-dose corticosteroids with a good clinical outcome.
CONCLUSION
Based upon available literature, the rate of CNS demyelinating events occurring in the setting of preceding or concurrent SARS-CoV-2 infection is relatively low considering the prevalence of SARS-CoV-2 infection. The clinical outcomes of new onset or relapsing MS, NMOSD, or MOGAD associated with antecedent or concurrent infection were mostly favorable. Larger prospective epidemiological studies are needed to better delineate the impact of COVID-19 on CNS demyelinating diseases.
PubMed: 36203986
DOI: 10.3389/fneur.2022.970383 -
The Cochrane Database of Systematic... Jan 2022Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with... (Review)
Review
BACKGROUND
Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with no objective loss of sensation. It may cause prolonged periods of disability. Treatment options for MMN are few. People with MMN do not usually respond to steroids or plasma exchange. Uncontrolled studies have suggested a beneficial effect of intravenous immunoglobulin (IVIg). This is an update of a Cochrane Review first published in 2005, with an amendment in 2007. We updated the review to incorporate new evidence.
OBJECTIVES
To assess the efficacy and safety of intravenous and subcutaneous immunoglobulin in people with MMN.
SEARCH METHODS
We searched the following databases on 20 April 2021: the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP for randomised controlled trials (RCTs) and quasi-RCTs, and checked the reference lists of included studies.
SELECTION CRITERIA
We considered RCTs and quasi-RCTs examining the effects of any dose of IVIg and subcutaneous immunoglobulin (SCIg) in people with definite or probable MMN for inclusion in the review. Eligible studies had to have measured at least one of the following outcomes: disability, muscle strength, or electrophysiological conduction block. We used studies that reported the frequency of adverse effects to assess safety.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed the literature searches to identify potentially relevant trials, assessed risk of bias of included studies, and extracted data. We followed standard Cochrane methodology.
MAIN RESULTS
Six cross-over RCTs including a total of 90 participants were suitable for inclusion in the review. Five RCTs compared IVIg to placebo, and one compared IVIg to SCIg. Four of the trials comparing IVIg versus placebo involved IVIg-naive participants (induction treatment). In the other two trials, participants were known IVIg responders receiving maintencance IVIg at baseline and were then randomised to maintenance treatment with IVIg or placebo in one trial, and IVIg or SCIg in the other. Risk of bias was variable in the included studies, with three studies at high risk of bias in at least one risk of bias domain. IVIg versus placebo (induction treatment): three RCTs including IVIg-naive participants reported a disability measure. Disability improved in seven out of 18 (39%) participants after IVIg treatment and in two out of 18 (11%) participants after placebo (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.89 to 10.12; 3 RCTs, 18 participants; low-certainty evidence). The proportion of participants with an improvement in disability at 12 months was not reported. Strength improved in 21 out of 27 (78%) IVIg-naive participants treated with IVIg and one out of 27 (4%) participants who received placebo (RR 11.00, 95% CI 2.86 to 42.25; 3 RCTs, 27 participants; low-certainty evidence). IVIg treatment may increase the proportion of people with resolution of at least one conduction block; however, the results were also consistent with no effect (RR 7.00, 95% CI 0.95 to 51.70; 4 RCTs, 28 participants; low-certainty evidence). IVIg versus placebo (maintenance treatment): a trial that included participants on maintenance IVIg treatment reported an increase in disability in 17 out of 42 (40%) people switching to placebo and seven out of 42 (17%) remaining on IVIg (RR 2.43, 95% CI 1.13 to 5.24; 1 RCT, 42 participants; moderate-certainty evidence) and a decrease in grip strength in 20 out of 42 (48%) participants after a switch to placebo treatment compared to four out of 42 (10%) remaining on IVIg (RR 0.20, 95% CI 0.07 to 0.54; 1 RCT, 42 participants; moderate-certainty evidence). Adverse events, IVIg versus placebo (induction or maintenance): four trials comparing IVIg and placebo reported adverse events, of which data from two studies could be meta-analysed. Transient side effects were reported in 71% of IVIg-treated participants versus 4.8% of placebo-treated participants in these studies. The pooled RR for the development of side effects was 10.33 (95% CI 2.15 to 49.77; 2 RCTs, 21 participants; very low-certainty evidence). There was only one serious side effect (pulmonary embolism) during IVIg treatment. IVIg versus SCIg (maintenance treatment): the trial that compared continuation of IVIg maintenance versus SCIg maintenance did not measure disability. The evidence was very uncertain for muscle strength (standardised mean difference 0.08, 95% CI -0.84 to 1.00; 1 RCT, 9 participants; very low-certainty evidence). The evidence was very uncertain for the number of people with side effects attributable to treatment (RR 0.50, 95% CI 0.18 to 1.40; 1 RCT, 9 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Low-certainty evidence from three small RCTs shows that IVIg may improve muscle strength in people with MMN, and low-certainty evidence indicates that it may improve disability; the estimate of the magnitude of improvement of disability has wide CIs and needs further studies to secure its significance. Based on moderate-certainty evidence, it is probable that most IVIg responders deteriorate in disability and muscle strength after IVIg withdrawal. SCIg might be an alternative treatment to IVIg, but the evidence is very uncertain. More research is needed to identify people in whom IVIg withdrawal is possible and to confirm efficacy of SCIg as an alternative maintenance treatment.
Topics: Humans; Immunoglobulins, Intravenous; Plasma Exchange; Polyneuropathies; Randomized Controlled Trials as Topic
PubMed: 35015296
DOI: 10.1002/14651858.CD004429.pub3 -
Orphanet Journal of Rare Diseases Aug 2023To understand the benefit-risk profile for historical and current treatments for MLD. (Review)
Review
A systematic review of clinical effectiveness and safety for historical and current treatment options for metachromatic leukodystrophy in children, including atidarsagene autotemcel.
OBJECTIVE
To understand the benefit-risk profile for historical and current treatments for MLD.
METHODS
A systematic review was conducted on the effectiveness, safety, and costs of MLD treatments: allogeneic haematopoietic stem cell transplantation (HSCT) and atidarsagene autotemcel (arsa-cel) according to best practice.
RESULTS
A total of 6940 titles and abstracts were retrieved from the literature searches and 26 from other sources. From these, 35 manuscripts reporting on a total of 12 studies were selected for inclusion in the review. There were no controlled multi-armed trials. However, we provide observations comparing two interventional therapies (alloHSCT and arsa-cel) and each of these to standard/supportive care (natural history). There were no benefits for survival, gross motor function and cognitive function for LI patients receiving alloHSCT, as patients experienced disease progression similar to LI natural history. For juvenile patients receiving alloHSCT, no differences in survival were observed versus natural history, however stabilisation of cognitive and motor function were reported for some patients (particularly for pre- or minimally-symptomatic LJ patients), while others experienced disease progression. Furthermore, alloHSCT was associated with severe complications such as treatment-related mortality, graft versus host disease, and re-transplantation in both LI and EJ treated patients. Most LI and EJ patients treated with arsa-cel appeared to have normal development, preservation, or slower progression of gross motor function and cognitive function, in contrast to the rapid decline observed in natural history patients. A survival benefit for arsa-cel versus natural history and versus alloHSCT was observed in LI patients.LI and EJ patients treated with arsa-cel had better gross motor function and cognitive function compared to alloHSCT, which had limited effect on motor and cognitive decline. No data has been reported for arsa-cel treatment of LJ patients.
CONCLUSIONS
Overall, this systematic review indicates that compared to NHx and HSCT, treatment with arsa-cel results in clinically relevant benefits in LI and EJ MLD patients by preserving cognitive function and motor development in most patients, and increased survival for LI patients. Nevertheless, further research is required to confirm these findings, given they are based on results from non-RCT studies.
Topics: Humans; Child; Leukodystrophy, Metachromatic; Treatment Outcome; Cognition; Cognitive Dysfunction; Disease Progression
PubMed: 37644601
DOI: 10.1186/s13023-023-02814-2 -
Journal of Neurology Mar 2024Case-reports/series and cohorts of Guillain-Barré syndrome (GBS) associated with COVID-19 vaccination have been reported. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Case-reports/series and cohorts of Guillain-Barré syndrome (GBS) associated with COVID-19 vaccination have been reported.
METHODS
A systematic review and meta-analysis of cohort studies of GBS after COVID-19 vaccination was carried out. Incidence and incidence rate ratio for a number of vaccine doses and risk of GBS, also considering the specific vaccine technology, were calculated in a random-effects model.
RESULTS
Of 554 citations retrieved, 518 were discarded as irrelevant. We finally included 15 studies. The random effect model yielded, regardless of the vaccine technology, 1.25 (95%CI 0.21; 2.83) GBS cases per million of COVID-19 vaccine doses, 3.93 (2.54; 5.54) cases per million doses for adenovirus-vectored vaccines and 0.69 (0.38; 1.06) cases per million doses for mRNA vaccines. The GBS risk was 2.6 times increased with the first dose. Regardless of the vaccine technology, the GBS risk was not increased but disaggregating the data it was 2.37 (1.67; 3.36) times increased for adenovirus-vectored vaccines and 0.32 (0.23; 0.47) for mRNA vaccines. Mortality for GBS after vaccination was 0.10 per million doses and 4.6 per GBS cases.
CONCLUSIONS
Adenovirus-vectored vaccines showed a 2.4 times increased risk of GBS that was about seven times higher compared with mRNA-based vaccines. The decreased GBS risk associated with mRNA vaccines was possibly due to an elicited reduction of infections, including SARS-CoV-2, associated with GBS during the vaccination period. How adenovirus-vectored COVID-19 vaccines may trigger GBS is unclear and further studies should investigate the relationship between vaccine technologies and GBS risk.
Topics: Humans; COVID-19; COVID-19 Vaccines; Guillain-Barre Syndrome; mRNA Vaccines; Vaccination
PubMed: 38233678
DOI: 10.1007/s00415-024-12186-7 -
Frontiers in Immunology 2023Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease... (Review)
Review
UNLABELLED
Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease progression remains to be deciphered. Biomarkers are needed to define pathophysiological processes of these disorders, who may increasingly co-exist in the elderly generations of the future, due to the rising prevalence in both and ameliorated treatment options with improved life expectancy in MS. The purpose of this review was to provide a systematic overview of inflammatory biomarkers, as measured in the cerebrospinal fluid (CSF), that are associated with clinical disease progression. International peer-reviewed literature was screened using the PubMed and Web of Science databases. Disease progression had to be measured using clinically validated tests representing baseline functional and/or cognitive status, the evolution of such clinical scores over time and/or the transitioning from one disease stage to a more severe stage. The quality of included studies was systematically evaluated using a set of questions for clinical, neurochemical and statistical characteristics of the study. A total of 84 papers were included (twenty-five for AD and 59 for MS). Elevated CSF levels of chitinase-3-like protein 1 (YKL-40) were associated with disease progression in both AD and MS. Osteopontin and monocyte chemoattractant protein-1 were more specifically related to disease progression in AD, whereas the same was true for interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic protein and IgG oligoclonal bands in MS. We observed a broad heterogeneity of studies with varying cohort characterization, non-disclosure of quality measures for neurochemical analyses and a lack of adequate longitudinal designs. Most of the retrieved biomarkers are related to innate immune system activity, which seems to be an important mediator of clinical disease progression in AD and MS. Overall study quality was limited and we have framed some recommendations for future biomarker research in this field.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42021264741.
Topics: Humans; Aged; Alzheimer Disease; Biomarkers; Disease Progression; Multiple Sclerosis
PubMed: 37520580
DOI: 10.3389/fimmu.2023.1162340 -
The Cochrane Database of Systematic... May 2022Ocrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration... (Review)
Review
BACKGROUND
Ocrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration (FDA) in March 2017 for using in adults with relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Ocrelizumab is the only disease-modifying therapy (DMT) approved for PPMS. In November 2017, the European Medicines Agency (EMA) also approved ocrelizumab as the first drug for people with early PPMS. Therefore, it is important to evaluate the benefits, harms, and tolerability of ocrelizumab in people with MS.
OBJECTIVES
To assess the benefits, harms, and tolerability of ocrelizumab in people with RRMS and PPMS.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL, and two trials registers on 8 October 2021. We screened reference lists, contacted experts, and contacted the main authors of studies.
SELECTION CRITERIA
All randomised controlled trials (RCTs) involving adults diagnosed with RRMS or PPMS according to the McDonald criteria, comparing ocrelizumab alone or associated with other medications, at the approved dose of 600 mg every 24 weeks for any duration, versus placebo or any other active drug therapy.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Four RCTs met our selection criteria. The overall population included 2551 participants; 1370 treated with ocrelizumab 600 mg and 1181 controls. Among the controls, 298 participants received placebo and 883 received interferon beta-1a. The treatment duration was 24 weeks in one study, 96 weeks in two studies, and at least 120 weeks in one study. One study was at high risk of allocation concealment and blinding of participants and personnel; all four studies were at high risk of bias for incomplete outcome data. For RRMS, compared with interferon beta-1a, ocrelizumab was associated with: 1. lower relapse rate (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.52 to 0.73; 2 studies, 1656 participants; moderate-certainty evidence); 2. a lower number of participants with disability progression (hazard ratio (HR) 0.60, 95% CI 0.43 to 0.84; 2 studies, 1656 participants; low-certainty evidence); 3. little to no difference in the number of participants with any adverse event (RR 1.00, 95% CI 0.96 to 1.04; 2 studies, 1651 participants; moderate-certainty evidence); 4. little to no difference in the number of participants with any serious adverse event (RR 0.79, 95% CI 0.57 to 1.11; 2 studies, 1651 participants; low-certainty evidence); 5. a lower number of participants experiencing treatment discontinuation caused by adverse events (RR 0.58, 95% CI 0.37 to 0.91; 2 studies, 1651 participants; low-certainty evidence); 6. a lower number of participants with gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) (RR 0.27, 95% CI 0.22 to 0.35; 2 studies, 1656 participants; low-certainty evidence); 7. a lower number of participants with new or enlarging T2-hyperintense lesions on MRI (RR 0.63, 95% CI 0.57 to 0.69; 2 studies, 1656 participants; low-certainty evidence) at 96 weeks. For PPMS, compared with placebo, ocrelizumab was associated with: 1. a lower number of participants with disability progression (HR 0.75, 95% CI 0.58 to 0.98; 1 study, 731 participants; low-certainty evidence); 2. a higher number of participants with any adverse events (RR 1.06, 95% CI 1.01 to 1.11; 1 study, 725 participants; moderate-certainty evidence); 3. little to no difference in the number of participants with any serious adverse event (RR 0.92, 95% CI 0.68 to 1.23; 1 study, 725 participants; low-certainty evidence); 4. little to no difference in the number of participants experiencing treatment discontinuation caused by adverse events (RR 1.23, 95% CI 0.55 to 2.75; 1 study, 725 participants; low-certainty evidence) for at least 120 weeks. There were no data for number of participants with gadolinium-enhancing T1 lesions on MRI and number of participants with new or enlarging T2-hyperintense lesions on MRI.
AUTHORS' CONCLUSIONS
For people with RRMS, ocrelizumab probably results in a large reduction in relapse rate and little to no difference in adverse events when compared with interferon beta-1a at 96 weeks (moderate-certainty evidence). Ocrelizumab may result in a large reduction in disability progression, treatment discontinuation caused by adverse events, number of participants with gadolinium-enhancing T1 lesions on MRI, and number of participants with new or enlarging T2-hyperintense lesions on MRI, and may result in little to no difference in serious adverse events (low-certainty evidence). For people with PPMS, ocrelizumab probably results in a higher rate of adverse events when compared with placebo for at least 120 weeks (moderate-certainty evidence). Ocrelizumab may result in a reduction in disability progression and little to no difference in serious adverse events and treatment discontinuation caused by adverse events (low-certainty evidence). Ocrelizumab was well tolerated clinically; the most common adverse events were infusion-related reactions and nasopharyngitis, and urinary tract and upper respiratory tract infections.
Topics: Adult; Antibodies, Monoclonal, Humanized; Gadolinium; Humans; Interferon beta-1a; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Recurrence
PubMed: 35583174
DOI: 10.1002/14651858.CD013247.pub2