Meta-analysis of adverse events in recent randomized clinical trials for dimethyl fumarate, glatiramer acetate and teriflunomide for the treatment of relapsing forms of multiple sclerosis

2014 ◽  
Vol 125 (11) ◽  
pp. 798-807 ◽  
Author(s):  
Francisco J. Zagmutt ◽  
Cathryn A. Carroll
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Adverse Events ◽  
Glatiramer Acetate ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Dimethyl Fumarate

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.

675 FUNDOPLICATION VERSUS ORAL PROTON PUMP INHIBITORS FOR GASTROESOPHAGEAL REFLUX DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Luca Schiliró Tristão ◽  
Francisco Tustumi ◽  
Guilherme Tavares ◽  
Letícia Nogueira Datrino ◽  
Maria Carolina Andrade Serafim ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Gastroesophageal Reflux Disease ◽  
Gastroesophageal Reflux ◽  
Adverse Events ◽  
Proton Pump ◽  
Reflux Disease ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Oral Intake

Abstract   Gastroesophageal reflux disease (GERD) is a widely studied and highly prevalent condition. However, few is reported about the exact efficacy and safety of fundoplication (FPT) compared to oral intake proton-pump inhibitors (PPI). This systematic review and meta-analysis of randomized clinical trials (RCT) aims to compare PPI and FPT in relation to the efficacy, as well as the adverse events associated with these therapies. Methods This systematic review was guided by PRISMA statement. Search carried out in June 2020 was conducted on Medline, Cochrane, EMBASE and LILACS. The inclusion criteria were (I) patients with GERD; (II) Randomized clinical trials, comparing oral intake PPI with FPT; (III) relevant outcomes for this review. The exclusion criteria were (I) reviews, case reports, editorials and letters (II) transoral or endoscopic FPT (III) studies with no full text. No restrictions were set for language or period. Certainty of evidence and risk of bias were assessed with GRADE Pro and with Review Manager Version 5.4 bias assessment tool. Results Ten RCT were included. Meta-analysis showed that heartburn (RD = −0.19; 95% CI = −0.29, −0.09) was less frequently reported by patients that underwent FPT. Furthermore, patients undergoing surgery had greater pressure on the lower esophageal sphincter than those who used PPI (MD = 7.81; 95% CI 4.79, 10.83). There was no significant difference between groups in the percentage of time with pH less than 4 in 24 hours, sustained remission and Gastrointestinal Symptom Rating Scale. Finally, FPT did not increase significantly the risk for adverse events such as postoperative dysphagia and impaired belching. Conclusion FPT is a more effective therapy than PPI treatment for GERD, without significantly increasing the risk for adverse events. However, before indicating a possible surgical approach, it is extremely important to correctly assess and select the patients who would benefit from FPT, such as those with severe erosive esophagitis, severe respiratory symptoms, low adherence to continuous drug treatment and patients with non-acid reflux, to ensure better results.

scholarly journals The Efficacy and Safety of Acellular Matrix Therapy for Diabetic Foot Ulcers: A Meta-Analysis of Randomized Clinical Trials

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Wentao Huang ◽  
Yongsong Chen ◽  
Nasui Wang ◽  
Guoshu Yin ◽  
Chiju Wei ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Healing Rate ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Complete Healing ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Efficacy And Safety ◽  
Acellular Matrix

Background. Acellular matrix (AM) therapy has shown promise in the treatment of diabetic foot ulcers (DFUs) in several studies. The clinical effects of AM therapy were not well established. Therefore, we conducted a meta-analysis of randomized clinical trials (RCTs) to examine the efficacy and safety of AM therapy for patients with DFUs. Methods. A literature search of 5 databases was performed to identify RCTs comparing AM therapy to standard therapy (ST) in patients with DFUs. The primary outcome was the complete healing rate and the secondary outcomes mainly included time to complete healing and adverse events. Results. Nine RCTs involving 897 patients were included. Compared with ST group, patients allocated to AM group had a higher complete healing rate both at 12 weeks (risk ratio RR=1.73, 95% confidence interval (CI): 1.31 to 2.30) and 16 weeks (RR=1.56, 95% CI: 1.28 to 1.91), a shorter time to complete healing (mean difference MD=−2.41; 95% CI: -3.49 to -1.32), and fewer adverse events (RR=0.64, 95% CI: 0.44 to 0.93). Conclusion. The present study suggests that AM therapy as an adjuvant treatment could further promote the healing of full-thickness, noninfected, and nonischemia DFUs. AM therapy also has a safety profile. More large well-designed randomized clinical trials with long follow-up duration are needed to further explore the efficacy and safety of AM therapy for DFUs.

Exercise training and cognitive performance in persons with multiple sclerosis: A systematic review and multilevel meta-analysis of clinical trials

2020 ◽  
pp. 135245852091793 ◽  
Author(s):  
Reza Gharakhanlou ◽  
Leonie Wesselmann ◽  
Annette Rademacher ◽  
Amit Lampit ◽  
Raoof Negaresh ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Exercise Training ◽  
Cognitive Performance ◽  
Randomized Clinical Trials ◽  
Selection Process ◽  
Meta Analysis ◽  
Training Dose ◽  
Domain Specific ◽  
Positive Effects

Background: Cognitive impairment is common, debilitating, and poorly managed in persons with multiple sclerosis (pwMS). Exercise training might have positive effects on cognitive performance in pwMS, yet the overall magnitude, heterogeneity, and potential moderators remain unclear. Objective: This three-level meta-analysis aims to identify the effects of exercise training and those of exercise modalities on global and domain-specific cognitive performance in pwMS. Methods: MEDLINE, PsycInfo, SportDiscus, CENTRAL, and EMBASE were screened for randomized and non-randomized clinical trials from inception to 27 January 2020, yielding 3091 articles. Based on titles and abstracts, 75 articles remained in the selection process. After full-text evaluation, 13 studies were finally selected (PROSPERO pre-registered). Results: The pooled effect of exercise training on the global cognitive performance was null ( g = 0.04, 95% confidence interval (CI): –0.11 to 0.18) and no significant differences were displayed among domains. Heterogeneity within studies was null ([Formula: see text]= 0.0%) and between studies was low ([Formula: see text]= 25.1%). None of the moderators (exercise modalities, age, Expanded Disability Status Scale (EDSS), supervision, cognitive domains) reached significance. However, the exercise volume explained most of the overall heterogeneity (slope = 4.651 × 10−5, [Formula: see text] = 100%, [Formula: see text] = 52.34%). Conclusion: These results do not support the efficacy of exercise training on global or domain-specific cognitive performance in pwMS. Future studies are needed to determine whether higher training dose are beneficial.

scholarly journals Comparison Outcomes of Discover Total Disk Arthroplasty and Anterior Cervical Discectomy with Fusion in Surgical Treatment of Cervical Disk Degenerative Disease: a Meta-Analysis of Randomized Trials

2018 ◽  
Vol 24 (4) ◽  
pp. 137-147
Author(s):  
V. A. Byvaltsev ◽  
I. A. Stepanov ◽  
M. A. Aliyev ◽  
B M. Avakov ◽  
B. R. Yussupov ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cervical Spine ◽  
Surgical Treatment ◽  
Adverse Events ◽  
Confidence Interval ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Degenerative Disease ◽  
Upper Limbs ◽  
Cervical Disk

The purpose —to compare the effectiveness of Discover cervical disk arthroplasty (CDA) and anterior cervical discectomy with fusion (ACDF) in the surgical treatment of cervical intervertebral disk (IVD) degenerative disease.Study design —a meta-analysis of randomized clinical trials.Material and Methods.Randomized clinical trials were conducted in the Pubmed, EMBASE, ELibrary and Cochrane Library databases published from 2008 to October 2018, which compared the results of Discover CDA and ACDF techniques in the surgical treatment of cervical IVD degenerative disease. For dichotomous variables, the relative risk and 95% confidence interval were calculated, standardized difference of mean values and their 95% confidence interval were used for continuous variables using the random effects model.Results.This meta-analysis included 9 randomized controlled clinical trials, including the results of surgical treatment of 513 patients with degenerative disease of the cervical IVD. In the CDA group, the operation time was significantly shorter, in contrast to the group of patients who underwent ACDF (p<0.0001). The values of blood loss (p = 0.89), levels of quality of life for patients according to the Neck Disability Index (NDI) (p = 0.22), severity of pain in the cervical spine (p = 0.50) and upper limbs on a visual analogue scale (VAS) (p = 0.16), as well as the prevalence of secondary surgical procedures (p = 0.68) and adverse events (p = 0.40) between the compared groups did not have significant differences. At the same time, significantly large values of the range of motion at the operated level were noted in the CDA group (p<0.00001).Conclusion.Discover CDA in comparison with ACDF has a significantly large values of range of motion at the operated level. At the same time, there were no statistically significant differences in the NDI scores, VAS pain scores in cervical spine and upper limbs, and the prevalence of secondary surgical procedures and adverse events between the compared groups of respondents were not identified.

scholarly journals Adverse Events Associated With Anti-IL-23 Agents: Clinical Evidence and Possible Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Ru ◽  
Xiaojie Ding ◽  
Ying Luo ◽  
Hongjin Li ◽  
Xiaoying Sun ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Event ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Cochrane Library ◽  
The Cochrane Library ◽  
Specific Symptoms

BackgroundAnti-interleukin (IL)-23 agents are widely used for autoimmune disease treatment; however, the safety and risks of specific symptoms have not been systematically assessed.ObjectivesThe aim of this study was to summarize the characteristics and mechanisms of occurrence of five immunological and non-immunological adverse events caused by different anti-IL-23 agents.MethodsThe Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched for eligible randomized clinical trials published from inception through May 1, 2020. Randomized clinical trials that reported at least one type of adverse event after treatment were included, regardless of sex, age, ethnicity, and diagnosis. Two investigators independently screened and extracted the characteristics of the studies, participants, drugs, and adverse event types. The Cochrane Handbook was used to assess the methodological quality of the included randomized clinical trials. Heterogeneity was assessed using the I2 statistic. Meta-regression was applied to determine the sources of heterogeneity, and subgroup analysis was used to identify the factors contributing to adverse events.ResultsForty-eight studies were included in the meta-analysis, comprising 25,624 patients treated with anti-IL-23 agents. Serious immunological or non-immunological adverse events were rare. Anti-IL-12/23-p40 agents appeared to cause adverse events more easily than anti-IL-23-p19 agents. The incidence of cancer did not appear to be related to anti-IL-23 agent treatment, and long-term medication could lead to mental diseases. The prevention of complications should be carefully monitored when administered for over approximately 40 weeks to avoid further adverse reactions, and the incidence of infection was the highest among general immunological adverse events.ConclusionsThe application of anti-IL-23 agents induced a series of immunological and non-immunological adverse events, but these agents tend to be well-tolerated with good safety profiles.

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