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.

scholarly journals Ozanimod for Treatment of Relapsing-Remitting Multiple Sclerosis in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 11 ◽  
Author(s):  
Yue Sun ◽  
Yanbo Yang ◽  
Zilan Wang ◽  
Fan Jiang ◽  
Zhouqing Chen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Adverse Events ◽  
Treatment Period ◽  
Relapse Rate ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Annualized Relapse Rate

Background: Ozanimod has been approved for use in the treatment of relapsing forms of multiple sclerosis by the United States FDA. As a novel, orally available sphingosine 1-phosphate receptor modulator, ozanimod selectively binds to S1P1 and S1P5 receptor with high affinity, minimizing safety concerns caused by S1P3 receptor activation.Methods: e systematically searched PUBMED, EMBASE database, and Cochrane Library database to identify randomized controlled trials (RCTs) from inception to June 28, 2020. Trials were considered eligible if they 1) were randomized clinical trials (RCTs); 2) enrolled adult participants diagnosed with Relapsing-remitting MS; 3) compared ozanimod with placebo or any other approved DMDs that evaluated in phase III or phase II clinical trials; 4) enrolled over 100 participants; 5) provided any available information for predefined primary or secondary outcomes.Results: 2917 participants from three high-quality, multi-centered randomized clinical trials were pooled in our analysis. We found that using ozanimod was significantly associated with the reduction of the annualized relapse rate during the treatment period (RR, −0.10 [95% CI, −0.15, −0.06]). Also, the decreased number of gadolinium-enhancing lesions at the end of the trial was relative to the treatment of ozanimod (ozanimod, 0.29; control, 0.65; RR, −0.20 [95% CI, −0.34, −0.06]). Compared with patients in the control group, the number of new or enlarging T2 lesions over the treatment period decreased in patients treated with ozanimod (ozanimod, 1.82; control, 3.55; RR, −1.12 [95% CI, −1.52, −0.71]). As to the safety endpoints, patients in the ozanimod group reported a lower rate of adverse events (ozanimod, 66.03%; control, 77.07%; RR, 0.64 [95% CI, 0.43, 0.95]). Similar incidence of infection-related TEAEs was found across treatment groups (nasopharyngitis: ozanimod, 11.19%; control, 9.83%; RR, 1.10 [95% CI, 0.77–1.57]; urinary-tract infection: ozanimod, 3.81%; control, 2.97%; RR, 1.29 [95% CI, 0.83–2.00]). No case of macular edema was noted as well as second-degree, type 2, or third-degree atrioventricular block. As for the subgroup analysis, compared with 0.5 mg ozanimod, 1 mg ozanimod is related with a significant reduction of the annualized relapse rate during the treatment period (1 mg ozanimod, 0.18; 0.5 mg ozanimod, 0.24; RR, 0.05 [95% CI, 0.01, 0.09])and a decreased number of new or enlarging T2 lesions over the treatment period (1 mg ozanimod,1.58; 0.5 mg ozanimod, 2.05; RR, 0.49 [95% CI, 0.19, 0.79]). No significant difference in causing adverse events between 1 and 0.5 mg was found.Conclusions: Our meta-analysis found that, with favorable safety performance, the use of ozanimod as a treatment of relapsing-remitting multiple sclerosis in adults was associated with a significant reduction of the annualized relapse rate during the treatment period, decreased number of gadolinium-enhancing lesions at the end of the trial, and lowered number of new or enlarging T2 lesions over the treatment period. Ozanimod 1 mg outperformed 0.5 mg dose in efficacy without increasing the risk of adverse events.

Ozanimod for the treatment of relapsing forms of multiple sclerosis

2021 ◽  
Author(s):  
Andrea M Kuczynski ◽  
Jiwon Oh
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Side Effects ◽  
Receptor Subtypes ◽  
Efficacy And Safety ◽  
S1p Receptors ◽  
Receptor Modulator ◽  
Wide Range ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Multiple sclerosis (MS) is an inflammatory disease that causes chronic neurological disability in young adults. Modulation of sphingosine 1-phosphate (S1P) receptors, a group of receptors that, among other things, regulate egression of lymphocytes from lymph nodes, has proven to be effective in treating relapsing MS. Fingolimod, the first oral S1P receptor modulator, has demonstrated potent efficacy and tolerability, but can cause undesirable side effects due to its interaction with a wide range of S1P receptor subtypes. This review will focus on ozanimod, a more selective S1P receptor modulator, which has recently received approval for relapsing MS. We summarize ozanimod’s mechanism of action, and efficacy and safety from clinical trials that demonstrate its utility as another treatment option for relapsing MS.

Effects of glatiramer acetate on relapse rate and accumulated disability in multiple sclerosis: meta-analysis of three double-blind, randomized, placebo-controlled clinical trials

2003 ◽  
Vol 9 (4) ◽  
pp. 349-355 ◽  
Author(s):  
Filippo Martinelli Boneschi ◽  
Marco Rovaris ◽  
Kenneth P Johnson ◽  
Aaron Miller ◽  
Jerry S Wolinsky ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Median Time ◽  
Relapse Rate ◽  
Meta Analysis ◽  
Study Entry ◽  
Clinical Variable ◽  
Double Blind ◽  
Annualized Relapse Rate ◽  
First Relapse

Three randomized, double-blind, placebo-controlled trials have shown that glatiramer acetate (GA) is effective in reducing relapse rate in patients with relapsing-remitting (RR) multiple sclerosis (MS). Using raw data pooled from 540 patients, we performed a meta-analysis of these three trials, to investigate whether the extent of G A efficacy varies according to disease-related variables at study entry. Three regression models were developed to assess the efficacy of G A on the annualized relapse rate (primary outcome measure), on the total number of on-trial relapses and on the time to first relapse. We also explored the efficacy of G A on accumulated disability and the potential role of baseline clinical variables as predicto rs of relapse-rate variables and treatment efficacy. The mean adjusted annualized relapse rate on study was 1.14 in the pooled placebo -treated subjects and 0.82 in the pooled GA group (P =0.004), indicating an average reductio n in annualized relapse rate of 28%. A bout a one third reductio n of the total number of on-trial relapses was also observed in patients receiving GA (P B-0.0001), who had a median time to the first relapse of 322 days versus a median time to the first relapse of 219 days seen in those receiving placebo (P =0.01). A beneficial effect on accumulated disability was also found (risk ratio of 0.6; 95%; C I =0.4-0.9; P =0.02). The drug assignment (P =0.004), baseline EDSS score (P =0.02) and number of relapses during the two years prior to study entry (P =0.002) were significant predicto rs of on-trial annualized relapse rate. No other demographic or clinical variable at baseline significantly influenced the treatment effect. This meta-analysis reaffirms the effectiveness of G A in reducing relapse rate and disability accumulatio n in RRMS, at a magnitude comparable to that of other available immunomodulating treatments. It also suggests that G A efficacy is not significantly influenced by the patients’ clinical characteristics at the time of treatment initiation.

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 Efficacy classification of modern therapies in multiple sclerosis

2021 ◽  
Author(s):  
Imtiaz A Samjoo ◽  
Evelyn Worthington ◽  
Christopher Drudge ◽  
Melody Zhao ◽  
Chris Cameron ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Meta Analysis ◽  
Comparative Trial ◽  
High Efficacy ◽  
Annualized Relapse Rate

Background: The Association of British Neurologists (ABN) 2015 guidelines suggested classifying multiple sclerosis therapies according to their average relapse reduction. We sought to classify newer therapies (cladribine, ocrelizumab, ofatumumab, ozanimod) based on these guidelines. Materials & methods: Therapies were classified by using direct comparative trial results as per ABN guidelines and generating classification probabilities for each therapy based on comparisons versus placebo in a network meta-analysis for annualized relapse rate. Results: For both approaches, cladribine and ofatumumab were classified as high efficacy. Ocrelizumab and ozanimod (1.0 mg) were classified as moderate or high efficacy depending on the approach used. Conclusion: Cladribine and ofatumumab have an efficacy comparable with therapies classified in the ABN guidelines as high efficacy.

Effect of antihypertensive drugs on cognition and behavioral symptoms of patients with Alzheimer’s disease: A meta-analysis

2020 ◽  
Vol 21 ◽  
Author(s):  
Roja Rahimi ◽  
Shekoufeh Nikfar ◽  
Masoud Sadeghi ◽  
Mohammad Abdollahi ◽  
Reza Heidary Moghaddam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Randomized Clinical Trials ◽  
Antihypertensive Drugs ◽  
Meta Analysis ◽  
Behavioral Symptoms ◽  
Cochrane Library ◽  
Mean Differences ◽  
Global Impression Of Change ◽  
State Examination

Background: It has been found that there is a link between hypertension and elevated risk of Alzheimer’s disease (AD). Herein, a meta-analysis based on randomized clinical trials (RCTs) was used to assess the effect of antihypertensive drugs on cognition and behavioral symptoms of AD patients. Method: The three databases – PubMed/Medline, Scopus, and Cochrane Library- were searched up to March 2020. The quality of the studies included in the meta-analysis was evaluated by the Jadad score. Clinical Global Impression of Change (CGIC) included in two studies, Mini-Mental State Examination (MMSE) included in three studies, and Neuropsychiatric Inventory (NPI) in three studies were the main outcomes in this systematic review. Results: Out of 1506 studies retrieved in the databases, 5 RCTs included and analyzed in the meta-analysis. The pooled mean differences of CGIC, MMSE, and NPI in patients with AD receiving antihypertensive drugs compared to placebo was -1.76 with (95% CI = -2.66 to -0.86; P=0.0001), 0.74 (95% CI = 0.20 to 1.28; P= 0.007), and -9.49 (95% CI = -19.76 to 0.79; P = 0.07), respectively. Conclusion: The findings of the present meta-analysis show that antihypertensive drugs may improve cognition and behavioral symptoms of patients with AD. However, more well-designed RCTs with similar drugs are needed to achieve more conclusive results.

scholarly journals Effect of somatometric parameters on the prevalence and severity of varicocele: a systematic review and meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Runqing Li ◽  
Junjie Liu ◽  
Yushan Li ◽  
Quanxian Wang
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Cochrane Library ◽  
China National Knowledge Infrastructure ◽  
Random Effects Models ◽  
Knowledge Infrastructure ◽  
Regression Test ◽  
Mean Differences ◽  
Q Statistic ◽  
The Relationship

Abstract Background Published studies have shown contradictory results regarding the relationship between somatometric parameters and varicoceles. We performed a systematic review and meta-analysis to investigate the possible effects of age, height, weight, and body mass index (BMI) on the presence and severity of varicoceles. Methods Databases including EMBASE, MEDLINE, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Web of Science, and Google Scholar were systematically searched to identify relevant articles published up to March 2020. Two researchers independently identified eligible articles and extracted data. Cochran’s Q statistic and I2 statistics were used to assess heterogeneity. Meta-analysis was performed using StataSE 12.0 software (StataCorp LP, USA). Random-effects models were used to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Publication bias was assessed using Begg’s funnel plot and Egger’s regression test. Results The search strategy produced 272 articles, of which 18 articles were eligible according to the inclusion/exclusion criteria. A total of 56,325 patients with varicocele and 1,334,694 patients without varicocele were included in the meta-analysis to evaluate the effect of somatometric parameters on the presence and severity of varicocele. The overall results demonstrated that the presence of varicoceles was significantly associated with height (WMD = 1.41, 95% CI = 1.07 to 1.74, P < 0.001) and inversely correlated with BMI (WMD = − 1.35, 95% CI = -1.67 to − 1.03, P < 0.001) but not with age (WMD = -0.93, 95% CI = -2.19 to 0.33, P = 0.149) or weight (WMD = 0.24, 95% CI = -2.24 to 2.72, P = 0.850). The severity of varicocele was inversely correlated with increased BMI but not with age. Conclusion The presence of varicoceles was significantly associated with height and inversely correlated with BMI.

scholarly journals Association between serum visfatin levels and psoriasis and their correlation with disease severity: a meta-analysis

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052110023
Author(s):  
Qian Zou ◽  
Jiawei Si ◽  
Yatao Guo ◽  
Jiayu Yu ◽  
Huijuan Shi
Keyword(s):  
Body Mass Index ◽  
Meta Analysis ◽  
Severity Index ◽  
Cochrane Library ◽  
Control Group ◽  
Inclusion Criteria ◽  
Subgroup Analyses ◽  
Mean Differences ◽  
The Cochrane Library ◽  
Psoriasis Severity

Objective To determine the association between serum visfatin levels and psoriasis and to evaluate the correlation between serum visfatin levels and the severity of psoriasis. Methods The electronic databases PubMed®, Embase® and the Cochrane Library were searched for articles published from inception to 1 May 2020. Data were extracted and then standard mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for pooled estimates. Results A total of 11 studies met the inclusion criteria and were included (448 patients diagnosed with psoriasis and 377 controls). This meta-analysis demonstrated that patients with psoriasis had significantly higher levels of visfatin than the controls (SMD = 0.90, 95% CI 0.52, 1.28). Subgroup analyses showed that differences in serum visfatin levels between the patient group and the control group were associated with ethnicity, Psoriasis Area and Severity Index (PASI) and body mass index. Additionally, a meta-analysis of correlations showed that visfatin levels in patients with psoriasis were positively correlated with PASI ( r = 0.51, 95% CI 0.14, 0.75). Conclusions This meta-analysis showed that serum visfatin levels in patients with psoriasis were significantly higher than those in the controls and a positive correlation between serum visfatin levels and psoriasis severity was observed.

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