Background A variety of novel monoclonal antibodies and immunosuppressant have been proved effective in treating Neuromyelitis Optica Spectrum Disorder (NMOSD). This network meta-analysis compared and ranked the efficacy and tolerability of currently used monoclonal antibodies and immunosuppressive agents in NMOSD. Methods Electronic database including PubMed, Embase and Cochrane Library were searched for relevant studies evaluating monoclonal antibodies and immunosuppressants in patients with NMOSD. The primary outcome measures were annualized relapse rate (ARR), relapse rate, the Expanded Disability Status Scale (EDSS) score, and total adverse events (AEs). Results We identified 25 studies with 2919 patients in our meta-analysis. For the primary outcome, rituximab (RTX) (SUCRA: 0.02) ranked first in reduction ARR with a significant difference compared with azathioprine (AZA) (MD – 0.34, 95% CrI – 0.55 to – 0.12) and mycophenolate mofetil (MMF) (MD –0.38, 95% CrI – 0.63 to – 0.14). Tocilizumab (SUCRA: 0.05) ranked first in relapse rate, which was superior to satralizumab (lnOR – 25.4, 95% CrI – 74.4 to – 2.49) and inebilizumab (lnOR – 24.86, 95% CrI – 73.75 to – 1.93). MMF (SUCRA: 0.27) had the fewest AEs followed by RTX (SUCRA: 0.35), both of which showed a significant difference compared with AZA and corticosteroids (MMF vs AZA: lnOR – 1.58, 95% CrI – 2.48 to – 0.68; MMF vs corticosteroids: lnOR – 1.34, 95% CrI – 2.3 to – 0.37) (RTX vs AZA: lnOR – 1.34, 95% CrI – 0.37 to – 2.3; RTX vs corticosteroids: lnOR – 2.52, 95% CrI – 0.32 to – 4.86). In EDSS score, no statistical difference was found between different interventions. Conclusion RTX and tocilizumab showed better efficacy than traditional immunosuppressants in reducing relapse. For safety, MMF and RTX had fewer AEs. However, studies with larger sample size on newly developed monoclonal antibodies are warranted in the future.
Review question / Objective: (1) participants: adult patients over 18 years with NMOSD; (2) intervention: monoclonal antibodies and immunosuppressants in patients with NMOSD; (3) outcomes: efficacy outcomes included annualized rate of relapse (ARR), EDSS score, relapse rates; Safety outcomes contains adverse events (AEs), gastrointestinal intolerance, leukopenia, hepatotoxicity; (4) study type: RCT and cohort studies. Condition being studied: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory neurological disorder which is common in neurological department. Current studies did not reveal the efficacy and safety of various monoclonal antibodies and immunosuppressants in patients with NMOSD. The aim of our study is to evaluate which drug intervention is the optimal therapy for NMOSD in controlling relapse, ARR and EDSS based on clinical evidence so far. In our study, we concluded the most effective and most safe drugs in NMOSD patients and made a rank probability of currently used antibodies and immunosuppressants. INPLASY registration number: This protocol was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) on 04 December 2022 and was last updated on 04 December 2022 (registration number INPLASY2022120018).
BackgroundParkinson's disease (PD) is a neurodegenerative disorder defined by progressive motor and non-motor symptoms. Currently, the pro-cognitive effects of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are well-supported in previous literatures. However, controversy surrounding the optimal therapeutic target for motor symptom improvement remains.ObjectiveThis network meta-analysis (NMA) was conducted to comprehensively evaluate the optimal strategy to use rTMS and tDCS to improve motor symptoms in PD.MethodsWe searched PubMed, Embase, and Cochrane electronic databases for eligible randomized controlled studies (RCTs). The primary outcome was the changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, the secondary outcomes were Time Up and Go Test (TUGT) time, and Freezing of Gait Questionnaire (FOGQ) score. The safety outcome was indicated by device-related adverse events (AEs).ResultWe enrolled 28 studies that investigated various strategies, including high-frequency rTMS (HFrTMS), low-frequency rTMS (LFrTMS), anodal tDCS (AtDCS), AtDCS_ cathode tDCS (CtDCS), HFrTMS_LFrTMS, and Sham control groups. Both HFrTMS (short-term: mean difference (MD) −5.21, 95% credible interval (CrI) −9.26 to −1.23, long-term: MD −4.74, 95% CrI −6.45 to −3.05), and LFrTMS (long-term: MD −4.83, 95% CrI −6.42 to −3.26) were effective in improving UPDRS-III score compared with Sham stimulation. For TUGT time, HFrTMS (short-term: MD −2.04, 95% CrI −3.26 to −0.8, long-term: MD −2.66, 95% CrI −3.55 to −1.77), and AtDCS (short-term: MD −0.8, 95% CrI −1.26 to −0.34, long-term: MD −0.69, 95% CrI −1.31 to −0.08) produced a significant difference compared to Sham stimulation. However, no statistical difference was found in FOGQ score among the various groups. According to the surface under curve ranking area, HFrTMS ranked first in short-term UPDRS-III score (0.77), short-term (0.82), and long-term (0.84) TUGT time, and short-term FOGQ score (0.73). With respect to the safety outcomes, all strategies indicated few and self-limiting AEs.ConclusionHFrTMS may be the optimal non-invasive brain stimulation (NIBS) intervention to improve motor function in patients with PD while NIBS has generally been well tolerated. However, further studies focusing on the clinical outcomes resulting from the different combined schedules of tDCS and rTMS are required.Systematic review registrationhttps://inplasy.com/inplasy-2023-4-0087/, identifier: 202340087.
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