The efficacy and safety of fingolimod in patients with relapsing multiple sclerosis: A meta‐analysis

Yang, Ting; Tian, Xin; Chen, Chao-Yang; Ma, Lei; Zhou, Shuang; Li, Min; Wu, Ye; Zhou, Ying; Chen, Yimin

doi:10.1111/bcp.14198

Cited by 17 publications

(11 citation statements)

References 39 publications

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“…With regard to the risk of arrhythmia induced by S1PRM use, our meta-analysis indicated that S1PRMs mainly increased the risk for bradyarrhythmia, a finding that is consistent with the results of several previous studies. One meta-analysis ( 37 ) published in 2020 evaluated the efficacy and safety of fingolimod in 10 RCTs and indicated that fingolimod use was associated with a significantly increased risk of bradycardia (RR, 3.92; 95% CI, 1.30–11.84), a finding that is consistent with our study. However, only bradycardia data were retrieved from that study, as its assessment of the risk of cardiovascular AEs was not comprehensive.…”

Section: Discussionsupporting

confidence: 91%

Risk for Cardiovascular Adverse Events Associated With Sphingosine-1-Phosphate Receptor Modulators in Patients With Multiple Sclerosis: Insights From a Pooled Analysis of 15 Randomised Controlled Trials

Zhao

et al. 2021

Front. Immunol.

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BackgroundAll agents engaging sphongosine-1-phospate receptors (S1PRs) will have some cardiovascular effect. This study aimed to elucidate the risk of cardiovascular adverse events (AEs) in patients with multiple sclerosis (MS) treated with S1PR modulators (S1PRMs).MethodsWe systematically searched the PubMed, EMBASE, and Cochrane Library databases for randomised controlled trials (RCTs) published through January 5, 2021. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. Sensitivity analyses and meta-regression were performed.ResultsSeventeen RCTs (12 for fingolimod; 3 for ozanimod; 2 for siponimod) involving 13,295 patients were included. Compared with the control treatment, S1PRMs significantly increased the risk of cardiovascular AEs (RR, 2.21; 95% CI, 1.58–3.10; I2, 75.6%). Notably, the high-risk cardiovascular AEs associated with S1PRMs were primarily bradyarrhythmia (RR, 2.92; 95% CI, 1.91–4.46; I2, 30.8%) and hypertension (RR, 2.00; 95% CI, 1.49–2.67; I2, 56.5%). Subgroup analysis results were consistent with the primary outcomes except that ozanimod was associated with a higher risk of hypertension only (RR, 1.76; 95% CI, 1.10–2.82; I2, 0.0%), while siponimod was associated with a higher risk of bradyarrhythmia only (RR, 2.75; 95% CI, 1.75–4.31; I2, 0.0%). No significant inter-subgroup differences were observed (Pinteraction > 0.05).ConclusionsS1PRM use increased the risk of cardiovascular AEs by 1.21 times in patients with MS, and increased risks for bradyarrhythmia and hypertension were at 2.92- and 2.00-fold, respectively. These findings can help clinicians assess the risk of cardiovascular AEs in patients treated with S1PRMs.Systematic Review RegistrationThe PROSPERO ID is CRD42020183215.

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Section: Discussionsupporting

confidence: 91%

Risk for Cardiovascular Adverse Events Associated With Sphingosine-1-Phosphate Receptor Modulators in Patients With Multiple Sclerosis: Insights From a Pooled Analysis of 15 Randomised Controlled Trials

Zhao

et al. 2021

Front. Immunol.

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“…In these studies, the overall incidence of adverse events (AEs) was counted, and no systematic analysis for specific adverse events (such as infection) was performed. At present, only one study in 2019 evaluated the efficacy and safety of fingolimod using 10 RCTs (27). In that study, bronchitis, nasopharyngitis, sinusitis, and urinary tract infection were considered infection events, and the analysis indicated that fingolimod was associated with a significantly increased risk of bronchitis, which was consistent with our result that fingolimod increased the risk of lower respiratory infection.…”

Section: Comparison With Previous Studiessupporting

confidence: 78%

Incidence and Risk of Infection Associated With Fingolimod in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis of 8,448 Patients From 12 Randomized Controlled Trials

Zhao

et al. 2021

Front. Immunol.

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Background and Aims: There is a controversy regarding whether fingolimod is associated with an increased risk of infection in patients with multiple sclerosis (MS). We performed a systematic review and meta-analysis of data from randomized controlled trials (RCTs) to determine the risk of infection in these patients.Methods: We systematically searched PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov from inception to April 8, 2020, to identify RCTs that reported the occurrence of infection in patients with MS treated with fingolimod. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using the random-effects model.Results: Twelve RCTs including 8,448 patients were eligible. Compared with the control (placebo and other active treatments), fingolimod significantly increased the risk of infection (RR, 1.16; 95% CI, 1.07–1.27; I2, 81%), regardless of whether the infection was a general infection (RR, 1.14; 95% CI, 1.05–1.25; I2, 78%), or a serious infection (RR, 1.49; 95% CI, 1.06–2.10; I2, 0%). Analyses of subgroups found that fingolimod significantly increased the risk of lower respiratory infection (RR, 1.48; 95% CI, 1.19–1.85; I2, 0%) and herpes virus infection (RR, 1.34; 95% CI, 1.01–1.78; I2, 9%). There appears to be no dose-dependent increase in the risk of infection associated with fingolimod (0.5 mg: RR, 1.15; 95% CI, 1.07–1.25; I2, 91%; 1.25 mg: RR, 1.11; 95% CI, 0.97–1.28; I2, 81%; Pinteraction = 0.66).Conclusions: Compared with a placebo and other active treatments, fingolimod was associated with a 16% increase in the risk of infection, especially lower respiratory infection and herpes virus infection. The risk of infection associated with fingolimod might not be dose related.

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“…To this end, the total number of relapses of all patients was calculated and divided by the total number of years of drug use to obtain the annual relapse rate of the patients. The obtained value was then divided by the number of patients using each drug in order to obtain the mean relapse rate of each drug (40,41).…”

Section: Effectivenessmentioning

confidence: 99%

The Clinical Effectiveness and Cost-Effectiveness of Rituximab Versus Natalizumab in Patients With Relapsing Remitting Multiple Sclerosis

Rezaee

Morowvat

Poursadeghfard

et al. 2021

Preprint

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Introduction: Multiple sclerosis (MS) is an inflammatory disease in which the myelin sheaths of the nerve cells in the brain and spinal cord, which are responsible for communication, are destroyed and cause physical signs and symptoms. According to studies, anti-CD20 monoclonal antibodies have significant results in the treatment of this disease. Thus, the aim of the present study was to determine the effectiveness and cost-effectiveness of Rituximab against Natalizumab in the patients with MS in southern Iran in 2020. Methods: This is an economic evaluation including cost-effectiveness analysis in which the Markov model with a lifetime horizon was used. The study sample consisted of 120 patients randomly selected from among those referred to the MS Association and the Special Diseases Unit of Shiraz University of Medical Sciences. In this study, the costs were collected from a societal perspective, and the outcomes were obtained in the form of Quality Adjusted Life Years (QALY) and the mean recurrence rate. The TreeAge pro 2020 and Excel 2016 software were used for data analysis. Results: The comparative study of Rituximab and Natalizumab showed that the patients receiving Rituximab had lower costs ($ 58307.931 vs. $ 354174.85) and more QALYs (7.77 vs. 7.65). In addition, the incidence of relapse by Rituximab was lower compared to Natalizumab (1.15 vs. 2.57). The probabilistic one-way sensitivity analysis showed the robustness of the results. The scatter plots also showed that Rituximab was more cost-effective for the patients in 100% of the simulations for the threshold of >$ 37,641. Discussion and Conclusion: According to the results of this study, Rituximab had higher cost-utility and cost-effectiveness than Natalizumab. Therefore, it could be a priority for MS patients compared to Natalizumab because it reduced treatment costs and increased effectiveness.

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The efficacy and safety of fingolimod in patients with relapsing multiple sclerosis: A meta‐analysis

Cited by 17 publications

References 39 publications

Risk for Cardiovascular Adverse Events Associated With Sphingosine-1-Phosphate Receptor Modulators in Patients With Multiple Sclerosis: Insights From a Pooled Analysis of 15 Randomised Controlled Trials

Risk for Cardiovascular Adverse Events Associated With Sphingosine-1-Phosphate Receptor Modulators in Patients With Multiple Sclerosis: Insights From a Pooled Analysis of 15 Randomised Controlled Trials

Incidence and Risk of Infection Associated With Fingolimod in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis of 8,448 Patients From 12 Randomized Controlled Trials

The Clinical Effectiveness and Cost-Effectiveness of Rituximab Versus Natalizumab in Patients With Relapsing Remitting Multiple Sclerosis

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