The effects of pregnancy on relapse rates, disability and peripartum outcomes in women with multiple sclerosis: a systematic review and meta-analysis

2021 ◽  
Vol 10 (3) ◽  
pp. 175-186
Author(s):  
Pedro J Modrego ◽  
Maria Añaños Urrea ◽  
Leyre Diaz de Cerio
Keyword(s):  
Multiple Sclerosis ◽  
Cohort Studies ◽  
Disease Activity ◽  
Relapse Rate ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Disability Progression ◽  
Obstetrical Outcomes ◽  
Lower Disease Activity ◽  
Relapse Rates

Background: Although previous cohort studies of women with multiple sclerosis (MS) yielded a reduction in relapse rate during pregnancy, the effect size has not been quantified in a comprehensive manner. In addition, the effects on disability progression and peripartum outcomes have been controversial. The purpose of this work is to assess the effect of pregnancy on disease activity, and to assess the effects of MS on pregnancy as well. Materials & methods: We searched in PubMed, Cochrane Library and EMBASE for cohort studies dealing with the effects of pregnancy on relapse rates, disability progression and peripartum outcomes in women with MS. The evaluated outcomes were: changes in the annualized relapse rate (ARR) in pregnancy and puerperium, disability worsening compared with the year before pregnancy, and peripartum outcomes, which were compared with the ones of non-MS women. In the majority of cohorts included here, the women were not under disease modifying therapies during pregnancy. Results: We found 23 cohort studies measuring changes in the ARR during pregnancy and puerperium; 12 were prospective and 11 retrospective. In 17 cohorts there was significant reduction in the ARR during pregnancy compared with prepregnancy period. The pooled mean reduction in the ARR was -0.5 (95% CI: 0.67–0.38), p < 0.001, from 15 cohorts included in meta-analysis. In 18 cohorts the ARR increased in the 3-month puerperium relative to prepregnancy year period; the pooled mean increase in the ARR was 0.22 (95% CI: 0.11–0.33), p < 0.001, from 14 cohorts included in meta-analysis. Disability worsening was addressed in 18 cohorts, and in 14 of them there were no significant changes. Peripartum complications and obstetrical outcomes were assessed in 16 cohorts, of whom 13 were retrospective, without finding significant differences. Conclusion: Pregnancy is associated with lower disease activity, and puerperium with higher disease activity. Disability does not change significantly after pregnancy. The obstetrical outcomes are not very different from those of non-MS women in most cohorts.

scholarly journals Real-world experience of fingolimod in patients with multiple sclerosis (MS Fine): An observational study in the UK

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731880163
Author(s):  
Gordon Mazibrada ◽  
Charlotte Sharples ◽  
Ines Perfect
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Observational Study ◽  
Disease Activity ◽  
Relapse Rate ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
The Uk ◽  
Relapsing Remitting Multiple Sclerosis

Background Fingolimod is approved for the treatment of highly active relapsing–remitting multiple sclerosis in Europe. There is limited information on its effectiveness and safety in clinical practice within the UK. Objective To evaluate retrospectively the effectiveness and safety of fingolimod in patients with relapsing–remitting multiple sclerosis who were prescribed fingolimod by UK neurologists within the National Health Service. Methods This was a multicentre, observational study conducted in the UK. Patients were initiated on fingolimod 0.5 mg 12 months before inclusion in the study. Key efficacy outcomes included annualised relapse rate and the proportion of patients free from relapses, disability progression and clinical and radiological disease activity at 12 months following fingolimod initiation. Resource utilisation and safety outcomes were also assessed. Results In 12 months of treatment with fingolimod, the mean annualised relapse rate was reduced by 79%, the majority of patients were free from relapses (83.7%). Based on limited data, most patients were free from disability progression and clinical and radiological disease activity. More than 90% of patients continued on fingolimod. Lymphocyte count reductions and liver enzyme increases were observed. Conclusion Fingolimod was effective in reducing the disease activity in relapsing–remitting multiple sclerosis patients requiring an escalation from first-line therapies who were prescribed fingolimod in clinical practice in the UK.

Course of relapsing–remitting multiple sclerosis before, during and after natalizumab

2010 ◽  
Vol 17 (4) ◽  
pp. 490-494 ◽  
Author(s):  
Michael D Kaufman ◽  
R Lee ◽  
HJ Norton
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Relapse Rate ◽  
Generalized Estimating Equations ◽  
Chart Review ◽  
Relapsing Remitting ◽  
Annualized Relapse Rate ◽  
Natalizumab Treatment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Relapse Rates

The consequences of interruption of natalizumab treatment are incompletely known. The objective was to assess the confirmed annualized relapse rates for patients preceding initiation, during and following suspension of natalizumab therapy. A chart review was conducted and data were analyzed using the Generalized Estimating Equations. During natalizumab therapy the confirmed annualized relapse rate was 0.08, compared to 0.52 ( p = 0.0003) during the prior 12 months and to 0.35 ( p = 0.0032) during the following 3 to 24 months. Similar results were found when confirmed and unconfirmed were analyzed. To conclude, following cessation of natalizumab therapy disease activity rapidly returned to pre-natalizumab levels.

scholarly journals Efficacy and acceptability of the S1P receptor in the treatment of multiple sclerosis: a meta-analysis

2021 ◽  
Author(s):  
Jingyi Tong ◽  
Qin Zou ◽  
Yongmin Chen ◽  
Xiaoping Liao ◽  
Rong Chen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Disease Modifying Drugs ◽  
S1p Receptors ◽  
Annualized Relapse Rate ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Mean Differences

Abstract Background and objective Sphingosine-1-phosphate (S1P) receptors are extensively used in the treatment of multiple sclerosis (MS). However, the optimal therapeutic role of S1P in MS patients has still remained elusive. This network meta-analysis (NMA) systematically evaluated the efficacy and acceptability of S1P receptors, as disease-modifying drugs, in the treatment of patients with MS, so as to find out the most appropriate therapeutic strategy and provide a reliable basis for the prescription of S1P drugs for patients with MS. Methods We conducted a systematic review and NMA to compare the efficacy and acceptability of S1P receptors for treating MS patients. Randomized controlled trials (RCTs), which were published until May 2020, were retrieved from the PubMed, Cochrane Library, Embase, and ClinicalTrials.gov databases. The primary outcome in this study was the treatment efficacy for the S1P receptor for MS patients, in terms of decrease in annualized relapse rate. The secondary outcomes were adverse events leading to discontinuation of a study, such as an unfavorable or unintended sign/symptom. Outcomes were appraised using a random effects model expressed as standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs), respectively, and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities for hierarchical clustering of interventions. Results A total of 13 RCTS were included, which enrolled 10,554 patients. The results of NMA showed that Fingolimod, Laquinimod, Siponimod, Ozanimod, Amiselimod, and Ponesimod were superior to placebo in terms of reducing the annualized relapse rate of MS patients. Regarding efficacy, the best and worst treatments were Amiselimod (0.4 mg; SUCRA 8.1%) and placebo (SUCRA 90.5%), respectively. As for acceptability, the best and worst interventions were Ozanimod (1 mg; SUCRA 20.4%) and Ponesimod (40 mg; SUCRA 96.0%), respectively. The comparison-adjusted funnel plots of annualized relapse rate and side effects in the included studies revealed that there was no significant funnel plot asymmetry Conclusions This NMA indicated that Amiselimod (0.4 mg) is the most effective treatment strategy as a S1P receptor for MS patients. However, the abovementioned findings need to be further confirmed in the next researches.

Prevalence and Risk Factors of Relapse in Patients with ANCA-Associated Vasculitis Receiving Cyclophosphamide Induction: A Systematic Review and Meta-analysis of Large Observational Studies

Rheumatology ◽  
2020 ◽  
Author(s):  
Peng He ◽  
Jin-ping Hu ◽  
Xiu-juan Tian ◽  
Li-jie He ◽  
Shi-ren Sun ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Baseline Serum ◽  
Anca Associated Vasculitis ◽  
Hazard Ratios ◽  
Post Hoc ◽  
Cumulative Probabilities ◽  
Relapse Rates

Abstract Background Clinical relapses are common in patients with ANCA-associated vasculitis (AAV). The aim of this systematic review was to estimate time-point prevalence and risk factors of relapse. Methods We searched PubMed, Embase, and Cochrane Library databases from their inception to March 30, 2020. Cohorts and post-hoc studies were included for the estimation of summary cumulative relapse rates (CRRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Sensitivity and meta-regression analyses were also performed. Results Of the 42 eligible studies, 24 studies with 6236 participants were used for the pooled analyses of CRRs. The summary 1-year, 3-year, and 5-year CRRs were 0.12 (95% CI, 0.10–0.14), 0.33 (0.29–0.38), and 0.47 (0.42–0.52), respectively. In meta-regressions, the baseline age was positively associated with 1-year CRR. The proportion of granulomatosis with polyangiitis was positively associated with 5-year CRR. Twenty-eight studies with 5390 participants were used for the meta-analysis of risk factors for relapse, including a lower level of baseline serum creatine, proteinase 3 (PR3)-ANCA positivity at diagnosis, an ANCA rise, extrarenal organ involvement (including lung, cardiovascular, upper respiratory, and gastrointestinal involvement), intravenous (vs oral) cyclophosphamide induction, a shorter course of immunosuppressant maintenance, and maintenance with mycophenolate mofetil (vs azathioprine). Conclusions Our systematic review demonstrated that the 1-year, 3-year, and 5-year cumulative probabilities of relapse were ∼12%, 33%, and 47% in AAV patients receiving cyclophosphamide induction, respectively. Early identification of risk factors for relapse is helpful to the risk stratification of patients so as to achieve personalized treatment.

scholarly journals Risk of dementia in gout and hyperuricaemia: a meta-analysis of cohort studies

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e041680
Author(s):  
Shu-Yue Pan ◽  
Rui-Juan Cheng ◽  
Zi-Jing Xia ◽  
Qiu-Ping Zhang ◽  
Yi Liu
Keyword(s):  
Cohort Studies ◽  
Quality Assessment ◽  
Publication Bias ◽  
Data Extraction ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
Crystal Formation ◽  
Medical Subject Headings ◽  
Eligibility Criteria

ObjectivesGout, characterised by hyperuricaemia with monosodium urate crystal formation and inflammation, is the most common inflammatory arthritis in adults. Recent studies have found that elevated uric acid levels are related to the occurrence of dementia. We conducted a study to investigate the association between dementia and gout or hyperuricaemia.DesignSystematic review and meta-analysis of cohort studies.Data sourcesStudies were screened from inception to 28 June 2019 by searching Medline, Embase and the Cochrane Library databases.Eligibility criteriaCohort studies comparing the risk of dementia in patients with gout and hyperuricaemia versus non-gout and non-hyperuricaemia controls were enrolled.Data extraction and analysisTwo reviewers separately selected studies and extracted data using the Medical Subject Headings without restriction on languages or countries. The adjusted HRs were pooled using the DerSimonian and Laird random effects model. Sensitivity analyses were conducted to evaluate the stability of the results. Publication bias was evaluated using Egger’s and Begg’s tests. Quality assessment was performed according to the Newcastle-Ottawa Scale.ResultsFour cohort studies that met the inclusion criteria were included in our meta-analysis. We found that gout and hyperuricaemia did not increase the risk of dementia, with a pooled HR of 0.94 (95% CI 0.69 to 1.28), but might decrease the risk of Alzheimer’s disease (AD), with a pooled HR of 0.78 (95% CI 0.64 to 0.95). There was little evidence of publication bias. Quality assessment of the included studies was high (range: 6–8 points).ConclusionsOur study shows that gout and hyperuricaemia do not increase the risk of dementia. However, gout and hyperuricaemia might have a protective effect against AD. Due to the limited number of research articles, more investigations are needed to demonstrate the potential relationship between dementia and gout or hyperuricaemia.

scholarly journals 2513. The Effect of Treatment Supporter Interventions on ART Adherence in Eastern and Southern Africa: a systematic review and meta-analysis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S872-S873
Author(s):  
Ya Haddy Sallah ◽  
Thabani Nyoni ◽  
Kim Lipsey
Keyword(s):  
Cohort Studies ◽  
Southern Africa ◽  
Meta Analysis ◽  
Standard Of Care ◽  
Cochrane Library ◽  
Virologic Suppression ◽  
Art Adherence ◽  
Meta Regression ◽  
Eastern And Southern Africa ◽  
Study Type

Abstract Background Access to ART has significantly reduced morbidity and mortality and improved quality of life in people living with HIV (PLWH). Treatment supporter interventions (TSIs) utilize patient or facility selected individuals to increase optimal ART adherence through home visits, peer support and medication management. This aim of this meta-analysis is to evaluate the effectiveness of TSIs in improving optimal ART adherence among PLWH in SSA using process- and outcome-oriented measures. Methods We searched PubMed, EMBASE, SCOPUS, Web of Science (WOS), Cochrane Library, and ClinicalTrials.gov for randomized controlled trials or cohort studies comparing treatment supporter interventions to the standard of care conducted in Eastern and Southern Africa. The primary outcomes were ART adherence measured by pill counts and virologic suppression. Pooled risk ratios with 95% confidence intervals were calculated using random-effects models. Stratified analyses and meta-regression were conducted to determine the effect of study type and patient nomination of treatment supporters on ART adherence. Results Sixteen studies, 10 RCTs and 6 cohort studies, were selected for inclusion. Virologic suppression was reported in 14 studies with 12,457 individuals in TSIs and 23,592 receiving the standard of care. Optimal ART adherence was reported in 7 RCTs only (2,185 individuals in TSI and 1,545 receiving SOC). Optimal ART adherence was 7.6% higher in TSIs compared with SOC (pooled RR 1.076, 95% CI 1.005–1.151, p = 0.035). Heterogeneity of these studies was high (I2 = 91.1%). Virologic suppression was 5% higher in TSIs compared with the standard of care (pooled RR 1.05, 95% CI 1.019–1.081, P = 0.001). Meta-regression demonstrated that virologic suppression did not significantly vary by study type (b = −0.042, 95% CI −0.09–0.001, P = 0.057) and patient selection of the treatment supporter (b = 0.026, 95% CI −0.07–0.12, P = 0.554). Conclusion Optimal ART adherence is marginally higher in treatment supporter interventions compared with the standard of care. Patient-nominated supporters achieve similar rates of virologic suppression to facility-selected supporters, and could play a critical role in addressing disparities in health outcomes among PLWH. Disclosures All authors: No reported disclosures.

scholarly journals Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS

2019 ◽  
pp. jnnp-2019-321124 ◽  
Author(s):  
Kumaran Deiva ◽  
Peter Huppke ◽  
Brenda Banwell ◽  
Tanuja Chitnis ◽  
Jutta Gärtner ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Phase Iii ◽  
Disability Progression ◽  
Double Blind ◽  
Younger Patients ◽  
Treatment Groups ◽  
Registration Number ◽  
Treatment Naïve ◽  
Post Hoc

BackgroundIn PARADIGMS, a double-blind phase III trial in 215 paediatric patients with multiple sclerosis (MS) (10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualised relapse rate (ARR) and rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a.ObjectivesTo investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression.MethodsARRs at 10, 11 and 12 years were estimated based on predefined modelling extrapolations. Changes in Expanded Disability Status Scale (EDSS), and in 3 month (3M) and 6 month (6M) confirmed disability progression (CDP) were evaluated post hoc.ResultsIn the treatment-naïve subpopulation, fingolimod reduced ARR and n/neT2 lesions by 85.8% and 53.4%, respectively versus INF β-1a (both p<0.001), compared with 81.9% and 52.6% in the overall population. Model-based ARR reductions in younger patients (≤12 years) were 91.9%–94.6%. Twice as many IFN β-1a-treated than fingolimod-treated patients had worse EDSS scores at study end (20.6% vs 10.5%, p=0.043). Risk reductions in 3M-CDP and 6M-CDP were 77.2% (p=0.007) and 80.2% (p=0.040), respectively.ConclusionsFingolimod in paediatric MS was associated with consistent control of disease activity versus IFN β-1a (including treatment-naïve and younger patients) and resulted in less disability progression for up to 2 years.Trial registration numberNCT01892722.

Impact of natural menopause on multiple sclerosis: a multicentre study

2019 ◽  
Vol 90 (11) ◽  
pp. 1201-1206 ◽  
Author(s):  
Damiano Baroncini ◽  
Pietro Osvaldo Annovazzi ◽  
Nicola De Rossi ◽  
Giulia Mallucci ◽  
Valentina Torri Clerici ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cigarette Smoking ◽  
Relapse Rate ◽  
Disability Progression ◽  
Natural Menopause ◽  
Multicentre Cohort Study ◽  
Disability Status ◽  
Speed Up ◽  
Multicentre Cohort

ObjectiveTo study the effect of natural menopause on multiple sclerosis clinical course.MethodsThis was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status.Results148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059).ConclusionNatural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.

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