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Arquivos de Neuro-psiquiatria Jun 2017The existence of a benign multiple sclerosis (BMS) form is a controversial subject. Recent studies of these patients reveal different levels of cognitive impairment,... (Review)
Review
The existence of a benign multiple sclerosis (BMS) form is a controversial subject. Recent studies of these patients reveal different levels of cognitive impairment, despite the apparent preservation of motor function. The objective of this study was to review and analyze a number of publications that discuss the general aspects of this disease form, such as the definition criteria, prevalence, and clinical and neuroimaging markers. A systematic review of published data on BMS up to October 2015 was performed. Thirty-one published articles were analyzed. The estimated frequency of BMS varied between 6% and 73%. Cognitive impairment was recognized as affecting 17% to 47% of the subjects and presented significant correlation with neuroimaging, such as brain atrophy, increased lesion volume in T2 magnetic resonance assay, and regional grey matter atrophy. The current criteria overestimated the frequency of BMS and, for that reason, this highlights the importance of validating the diagnostic methods practiced.
Topics: Cognition Disorders; Humans; Multiple Sclerosis; Neuroimaging
PubMed: 28658410
DOI: 10.1590/0004-282X20170043 -
The Cochrane Database of Systematic... Dec 2011Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. Statins, prescribed as cholesterol lowering agents, have shown... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. Statins, prescribed as cholesterol lowering agents, have shown possible effects for treating MS in experimental and preliminary clinical studies.
OBJECTIVES
To evaluate the efficacy and safety of statins administered alone or as add-on to approved treatments for MS.
SEARCH METHODS
The Trials Search Coordinator searched the Cochrane MS Group Trials Register (1 August 2011). We searched the Chinese National Knowledge Infrastructure (CNKI) (1979 to 1 August 2011), trials registers and conference proceedings. Pharmaceutical companies and authors of included studies were contacted for additional information.There were no language restrictions.
SELECTION CRITERIA
Randomised controlled trials comparing statins with placebo, or comparing statins in combination with approved treatments alone for patients with MS.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed trial quality and extracted data.
MAIN RESULTS
Four trials involving 458 participants were included. All trials compared statins (two evaluating atorvastatin and two simvastatin) plus interferon beta-1a with interferon beta-1a alone for treating MS. The methodological quality was good for three studies and poor for remaining one. None of them showed statistically significant difference between both treatment groups in reducing relapses, preventing disease progression or developing new T2 or gadolinium-enhanced lesions on MRI after 9, 12, 24 months follow up period. Statins resulted to be safe and well tolerated, no serious adverse effects were reported. Changes on quality of life after receiving statins were not reported in the trials.
AUTHORS' CONCLUSIONS
There is no convincing evidence to support the use of either atorvastatin or simvastatin as an adjunctive therapy in MS.
Topics: Atorvastatin; Disease Progression; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interferon-beta; Multiple Sclerosis; Pyrroles; Randomized Controlled Trials as Topic; Secondary Prevention; Simvastatin
PubMed: 22161428
DOI: 10.1002/14651858.CD008386.pub3 -
The Cochrane Database of Systematic... Apr 2015Telerehabilitation, an emerging method, extends rehabilitative care beyond the hospital, and facilitates multifaceted, often psychotherapeutic approaches to modern... (Review)
Review
BACKGROUND
Telerehabilitation, an emerging method, extends rehabilitative care beyond the hospital, and facilitates multifaceted, often psychotherapeutic approaches to modern management of patients using telecommunication technology at home or in the community. Although a wide range of telerehabilitation interventions are trialed in persons with multiple sclerosis (pwMS), evidence for their effectiveness is unclear.
OBJECTIVES
To investigate the effectiveness and safety of telerehabilitation intervention in pwMS for improved patient outcomes. Specifically, this review addresses the following questions: does telerehabilitation achieve better outcomes compared with traditional face-to-face intervention; and what types of telerehabilitation interventions are effective, in which setting and influence which specific outcomes (impairment, activity limitation and participation)?
SEARCH METHODS
We performed a literature search using the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Review Group Specialised Register( 9 July, 2014.) We handsearched the relevant journals and screened the reference lists of identified studies, and contacted authors for additional data.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) that reported telerehabilitation intervention/s in pwMS and compared them with some form of control intervention (such as lower level or different types of intervention, minimal intervention, waiting-list controls or no treatment (or usual care); interventions given in different settings) in adults with MS.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data. Three review authors assessed the methodological quality of studies using the GRADEpro software (GRADEpro 2008) for best-evidence synthesis. A meta-analysis was not possible due to marked methodological, clinical and statistical heterogeneity between included trials and between measurement tools used. Hence, we performed a best-evidence synthesis using a qualitative analysis.
MAIN RESULTS
Nine RCTs, one with two reports, (N = 531 participants, 469 included in analyses) investigated a variety of telerehabilitation interventions in adults with MS. The mean age of participants varied from 41 to 52 years (mean 46.5 years) and mean years since diagnosis from 7.7 to 19.0 years (mean 12.3 years). The majority of the participants were women (proportion ranging from 56% to 87%, mean 74%) and with a relapsing-remitting course of MS. These interventions were complex, with more than one rehabilitation component and included physical activity, educational, behavioural and symptom management programmes.All studies scored 'low' on the methodological quality assessment. Overall, the review found 'low-level' evidence for telerehabilitation interventions in reducing short-term disability and symptoms such as fatigue. There was also 'low-level' evidence supporting telerehabilitation in the longer term for improved functional activities, impairments (such as fatigue, pain, insomnia); and participation measured by quality of life and psychological outcomes. There were limited data on process evaluation (participants'/therapists' satisfaction) and no data available for cost effectiveness. There were no adverse events reported as a result of telerehabilitation interventions.
AUTHORS' CONCLUSIONS
There is currently limited evidence on the efficacy of telerehabilitation in improving functional activities, fatigue and quality of life in adults with MS. A range of telerehabilitation interventions might be an alternative method of delivering services in MS populations. There is insufficient evidence to support on what types of telerehabilitation interventions are effective, and in which setting. More robust trials are needed to build evidence for the clinical and cost effectiveness of these interventions.
Topics: Adult; Humans; Middle Aged; Multiple Sclerosis; Randomized Controlled Trials as Topic; Telemedicine; Treatment Outcome
PubMed: 25854331
DOI: 10.1002/14651858.CD010508.pub2 -
BMC Neurology Jun 2019Multiple sclerosis (MS) and stroke are two common causes of death and disability worldwide. The relationship between these two diseases remains unclear. Effective early... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple sclerosis (MS) and stroke are two common causes of death and disability worldwide. The relationship between these two diseases remains unclear. Effective early preventative measures and treatments are available to reduce the morbidity and mortality of acute stroke. The objectives of our systematic review are to estimate the risk of stroke in patients with MS and to collate related studies to draw preliminary conclusions that may improve clinical practice.
METHOD
Relevant studies were systematically searched in MEDLINE, Embase, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure and the VIP database of Chinese periodicals from January 1983 to May 2017, with no restrictions on language. Patients included in this review were adults who suffered from MS. Review Manager 5.3 software program was used to pool data and calculate the risk ratio (RR) and its 95% confidence interval (CI). We also performed heterogeneity and sensitivity analyses and evaluated bias in the meta-analysis.
RESULTS
Nine studies including more than 380,000 participants that met our inclusion criteria were incorporated into the meta-analysis. During different follow-up periods, patients with MS had an increased risk of any type of stroke [RR = 3.48, 95% CI (1.59, 7.64), P = 0.002 for 1 year; RR = 2.45, 95% CI (1.90, 3.16), P < 0.00001 for 10-13 years]. The total prevalence of stroke (any type) in patients with MS exceeded expectations compared to different groups [Comparing with general veteran: RR = 2, 95% CI (1.19, 3.38), P = 0.009. Comparing with general population: RR = 2.93, 95% CI (1.13, 7.62), P = 0.03]. Furthermore, ischemic stroke was particularly more common in the MS population than in people without MS [RR = 6.09, 95% CI (3.44, 10.77), P < 0.00001].
CONCLUSION
Compared with the general population, people with MS have an increased risk of developing any type of stroke and ischemic stroke in particular. Consistent results were obtained from patients of different sexes and age groups. Preventative measures and treatments should be administered at earlier time points to improve patient outcomes.
Topics: China; Comorbidity; Humans; Multiple Sclerosis; Stroke
PubMed: 31234793
DOI: 10.1186/s12883-019-1366-7 -
JAMA Neurology Jun 2023Progressive multifocal leukoencephalopathy can occur in the context of systemic sarcoidosis (S-PML) in the absence of therapeutic immune suppression and can initially be...
IMPORTANCE
Progressive multifocal leukoencephalopathy can occur in the context of systemic sarcoidosis (S-PML) in the absence of therapeutic immune suppression and can initially be mistaken for neurosarcoidosis or other complications of sarcoidosis. Earlier recognition of S-PML could lead to more effective treatment of the disease.
OBJECTIVE
To describe characteristics of patients with S-PML.
DESIGN, SETTING, AND PARTICIPANTS
For this case series, records from 8 academic medical centers in the United States were reviewed from 2004 to 2022. A systematic review of literature from 1955 to 2022 yielded data for additional patients. Included were patients with S-PML who were not receiving therapeutic immune suppression. The median follow-up time for patients who survived the acute range of illness was 19 months (range, 2-99). Data were analyzed in February 2023.
EXPOSURES
Sarcoidosis without active therapeutic immune suppression.
MAIN OUTCOMES AND MEASURES
Clinical, laboratory, and radiographic features of patients with S-PML.
RESULTS
Twenty-one patients with S-PML not receiving therapeutic immune suppression were included in this study, and data for 37 patients were collected from literature review. The median age of the 21 study patients was 56 years (range, 33-72), 4 patients (19%) were female, and 17 (81%) were male. The median age of the literature review patients was 49 years (range, 21-74); 12 of 34 patients (33%) with reported sex were female, and 22 (67%) were male. Nine of 21 study patients (43%) and 18 of 31 literature review patients (58%) had simultaneous presentation of systemic sarcoidosis and PML. Six of 14 study patients (43%) and 11 of 19 literature review patients (58%) had a CD4+ T-cell count greater than 200/μL. In 2 study patients, a systemic flare of sarcoidosis closely preceded S-PML development. Ten of 17 study patients (59%) and 21 of 35 literature review patients (60%) died during the acute phase of illness. No meaningful predictive differences were found between patients who survived S-PML and those who did not.
CONCLUSIONS AND RELEVANCE
In this case series, patients with sarcoidosis developed PML in the absence of therapeutic immune suppression, and peripheral blood proxies of immune function were often only mildly abnormal. Systemic sarcoidosis flares may rarely herald the onset of S-PML. Clinicians should consider PML in any patient with sarcoidosis and new white matter lesions on brain magnetic resonance imaging.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Young Adult; Leukoencephalopathy, Progressive Multifocal; Brain; Sarcoidosis; Magnetic Resonance Imaging; Treatment Outcome
PubMed: 37093609
DOI: 10.1001/jamaneurol.2023.0841 -
Journal of Neurology Sep 2021Neurofilament proteins have been extensively studied in relapsing-remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment... (Review)
Review
BACKGROUND
Neurofilament proteins have been extensively studied in relapsing-remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment response. Their role in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers, is less clear. The objectives of this systematic review are to summarise the literature on neurofilament light and heavy in progressive multiple sclerosis, addressing key questions.
METHODS
A systematic search of PubMed, Embase, Web of Science and Scopus identified 355 potential sources. 76 relevant sources were qualitatively reviewed using QUADAS-2 criteria, and 17 were identified as at low risk of bias. We summarise the findings from all relevant sources, and separately from the 17 high-quality studies.
RESULTS
Differences in neurofilament light between relapsing-remitting and progressive multiple sclerosis appear to be explained by differences in covariates. Neurofilament light is consistently associated with current inflammatory activity and future brain atrophy in progressive multiple sclerosis, and is consistently shown to be a marker of treatment response with immunosuppressive disease-modifying therapies. Associations with current or future disability are inconsistent, and there is no evidence of NFL being a responsive marker of purportedly neuroprotective treatments. Evidence on neurofilament heavy is more limited and inconsistent.
CONCLUSIONS
Neurofilament light has shown consistent utility as a biomarker of neuroinflammation, future brain atrophy and immunosuppressive treatment response at a group level. Neither neurofilament light or heavy has shown a consistent treatment response to neuroprotective disease-modifying therapies, which will require further data from successful randomised controlled trials.
Topics: Biomarkers; Humans; Intermediate Filaments; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Neurofilament Proteins
PubMed: 32447549
DOI: 10.1007/s00415-020-09917-x -
Neurology Apr 2016We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS).
OBJECTIVE
We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS).
METHODS
We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS.
RESULTS
We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies.
CONCLUSION
Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to "real world" settings where the MS population commonly has comorbid conditions.
Topics: Clinical Trials as Topic; Comorbidity; Humans; Multiple Sclerosis
PubMed: 26888986
DOI: 10.1212/WNL.0000000000002471 -
BMC Neurology May 2013Although the precise etiology of multiple sclerosis is largely unknown, there is some speculation that a prior history of surgery may be associated with the subsequent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although the precise etiology of multiple sclerosis is largely unknown, there is some speculation that a prior history of surgery may be associated with the subsequent risk for developing the disease. Therefore, we aimed to examine surgery as a risk factor for the diagnosis of multiple sclerosis.
METHODS
We searched for observational studies that evaluated the risk for developing multiple sclerosis after surgery that occurred in childhood (≤ 20 years of age) or "premorbid" (> 20 years of age). We specifically included surgeries classified as: tonsillectomy, appendectomy, adenoidectomy, or "surgery". We performed a systematic review and meta-analyses and calculated odds ratios (OR) and their 95% confidence intervals (CIs) using a random effects model.
RESULTS
We identified 33 case-control studies, involving 27,373 multiple sclerosis cases and 211,756 controls. There was a statistically significant association between tonsillectomy (OR = 1.32, 95% CI 1.08-1.61; 12 studies, I(2) = 44%) and appendectomy (OR = 1.16, 95% CI 1.01-1.34; 7 studies, I(2) = 0%) in individual's ≤ 20 years of age and the subsequent risk for developing multiple sclerosis. There was no statistically significant association between risk for multiple sclerosis and tonsillectomy occurring after age 20 (OR = 1.20, 95% CI 0.94-1.53; 9 studies, I(2) = 32%), in those with appendectomy at > 20 years (OR = 1.26, 95% CI 0.92-1.72; 5 studies, I(2) = 46%), and in those with adenoidectomy at ≤ 20 years of age (OR = 1.06, 95% CI 0.68-1.68; 3 studies, I(2) = 35%). The combined OR of 15 studies (N = 2,380) looking at "surgery" before multiple sclerosis diagnosis was not statistically significant (OR = 1.19, 95% CI 0.83-1.70; I(2) = 71%).
CONCLUSIONS
We found a small but statistically significant and clinically important increased risk for developing multiple sclerosis, in those with tonsillectomy and appendectomy at ≤ 20 years of age. There was no convincing evidence to support the association of other surgeries and the risk for multiple sclerosis. Well-designed prospective etiological studies, pertaining to the risk for developing multiple sclerosis, ought to be conducted and should include the examination of various surgeries as risk factors.
Topics: Case-Control Studies; Databases, Factual; Humans; Multiple Sclerosis; Risk Factors
PubMed: 23648120
DOI: 10.1186/1471-2377-13-41 -
The Cochrane Database of Systematic... May 2012Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS... (Review)
Review
BACKGROUND
Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients.
OBJECTIVES
To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose.
SEARCH METHODS
A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied.
SELECTION CRITERIA
Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included.
DATA COLLECTION AND ANALYSIS
Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up.
MAIN RESULTS
The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active-comparator, cross-over trial. In the completed study, adult patients with relapsing-remitting and secondary progressive MS were exposed to both acetyl L-carnitine 2 grams daily and amantadine 200 mg daily The effects of carnitine on fatigue are unclear. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious adverse event in either treatment group. Mortality and quality of life were not reported.
AUTHORS' CONCLUSIONS
There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.
Topics: Acetylcarnitine; Adult; Amantadine; Fatigue; Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic; Vitamin B Complex
PubMed: 22592719
DOI: 10.1002/14651858.CD007280.pub3 -
The Cochrane Database of Systematic... Nov 2021Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the International Federation of MS, including high-income countries where on-label disease-modifying treatments (DMTs) are available. OBJECTIVES: To assess beneficial and adverse effects of rituximab as 'first choice' and as 'switching' for adults with MS.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registers for completed and ongoing studies on 31 January 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and controlled non-randomised studies of interventions (NRSIs) comparing rituximab with placebo or another DMT for adults with MS.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. We used the Cochrane Collaboration's tool for assessing risk of bias. We rated the certainty of evidence using GRADE for: disability worsening, relapse, serious adverse events (SAEs), health-related quality of life (HRQoL), common infections, cancer, and mortality. We conducted separate analyses for rituximab as 'first choice' or as 'switching', relapsing or progressive MS, comparison versus placebo or another DMT, and RCTs or NRSIs.
MAIN RESULTS
We included 15 studies (5 RCTs, 10 NRSIs) with 16,429 participants of whom 13,143 were relapsing MS and 3286 progressive MS. The studies were one to two years long and compared rituximab as 'first choice' with placebo (1 RCT) or other DMTs (1 NRSI), rituximab as 'switching' against placebo (2 RCTs) or other DMTs (2 RCTs, 9 NRSIs). The studies were conducted worldwide; most originated from high-income countries, six from the Swedish MS register. Pharmaceutical companies funded two studies. We identified 14 ongoing studies. Rituximab as 'first choice' for relapsing MS Rituximab versus placebo: no studies met eligibility criteria for this comparison. Rituximab versus other DMTs: one NRSI compared rituximab with interferon beta or glatiramer acetate, dimethyl fumarate, natalizumab, or fingolimod in active relapsing MS at 24 months' follow-up. Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (hazard ratio (HR) 0.14, 95% confidence interval (CI) 0.05 to 0.39; 335 participants; moderate-certainty evidence). Rituximab may reduce relapses compared with dimethyl fumarate (HR 0.29, 95% CI 0.08 to 1.00; 206 participants; low-certainty evidence) and natalizumab (HR 0.24, 95% CI 0.06 to 1.00; 170 participants; low-certainty evidence). It may make little or no difference on relapse compared with fingolimod (HR 0.26, 95% CI 0.04 to 1.69; 137 participants; very low-certainty evidence). The study reported no deaths over 24 months. The study did not measure disability worsening, SAEs, HRQoL, and common infections. Rituximab as 'first choice' for progressive MS One RCT compared rituximab with placebo in primary progressive MS at 24 months' follow-up. Rituximab likely results in little to no difference in the number of participants who have disability worsening compared with placebo (odds ratio (OR) 0.71, 95% CI 0.45 to 1.11; 439 participants; moderate-certainty evidence). Rituximab may result in little to no difference in recurrence of relapses (OR 0.60, 95% CI 0.18 to 1.99; 439 participants; low-certainty evidence), SAEs (OR 1.25, 95% CI 0.71 to 2.20; 439 participants; low-certainty evidence), common infections (OR 1.14, 95% CI 0.75 to 1.73; 439 participants; low-certainty evidence), cancer (OR 0.50, 95% CI 0.07 to 3.59; 439 participants; low-certainty evidence), and mortality (OR 0.25, 95% CI 0.02 to 2.77; 439 participants; low-certainty evidence). The study did not measure HRQoL. Rituximab versus other DMTs: no studies met eligibility criteria for this comparison. Rituximab as 'switching' for relapsing MS One RCT compared rituximab with placebo in relapsing MS at 12 months' follow-up. Rituximab may decrease recurrence of relapses compared with placebo (OR 0.38, 95% CI 0.16 to 0.93; 104 participants; low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to placebo on SAEs (OR 0.90, 95% CI 0.28 to 2.92; 104 participants; very low-certainty evidence), common infections (OR 0.91, 95% CI 0.37 to 2.24; 104 participants; very low-certainty evidence), cancer (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence), and mortality (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence). The study did not measure disability worsening and HRQoL. Five NRSIs compared rituximab with other DMTs in relapsing MS at 24 months' follow-up. The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to interferon beta or glatiramer acetate on disability worsening (HR 0.86, 95% CI 0.52 to 1.42; 1 NRSI, 853 participants; very low-certainty evidence). Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (HR 0.18, 95% CI 0.07 to 0.49; 1 NRSI, 1383 participants; moderate-certainty evidence); and fingolimod (HR 0.08, 95% CI 0.02 to 0.32; 1 NRSI, 256 participants; moderate-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to natalizumab on relapses (HR 1.0, 95% CI 0.2 to 5.0; 1 NRSI, 153 participants; very low-certainty evidence). Rituximab likely increases slightly common infections compared with interferon beta or glatiramer acetate (OR 1.71, 95% CI 1.11 to 2.62; 1 NRSI, 5477 participants; moderate-certainty evidence); and compared with natalizumab (OR 1.58, 95% CI 1.08 to 2.32; 2 NRSIs, 5001 participants; moderate-certainty evidence). Rituximab may increase slightly common infections compared with fingolimod (OR 1.26, 95% CI 0.90 to 1.77; 3 NRSIs, 5187 participants; low-certainty evidence). It may make little or no difference compared with ocrelizumab (OR 0.02, 95% CI 0.00 to 0.40; 1 NRSI, 472 participants; very low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab on mortality compared with fingolimod (OR 5.59, 95% CI 0.22 to 139.89; 1 NRSI, 136 participants; very low-certainty evidence) and natalizumab (OR 6.66, 95% CI 0.27 to 166.58; 1 NRSI, 153 participants; very low-certainty evidence). The included studies did not measure SAEs, HRQoL, and cancer.
AUTHORS' CONCLUSIONS
For preventing relapses in relapsing MS, rituximab as 'first choice' and as 'switching' may compare favourably with a wide range of approved DMTs. A protective effect of rituximab against disability worsening is uncertain. There is limited information to determine the effect of rituximab for progressive MS. The evidence is uncertain about the effect of rituximab on SAEs. They are relatively rare in people with MS, thus difficult to study, and they were not well reported in studies. There is an increased risk of common infections with rituximab, but absolute risk is small. Rituximab is widely used as off-label treatment in people with MS; however, randomised evidence is weak. In the absence of randomised evidence, remaining uncertainties on beneficial and adverse effects of rituximab for MS might be clarified by making real-world data available.
Topics: Fingolimod Hydrochloride; Glatiramer Acetate; Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Rituximab; Young Adult
PubMed: 34748215
DOI: 10.1002/14651858.CD013874.pub2