The efficacy and safety of FcRn inhibitors in patients with myasthenia gravis: a systematic review and meta-analysis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease that causes local or generalized muscle weakness. Complement inhibitors and targeting of the neonatal Fc receptor (FcRn) to block IgG cycling are two novel and successful mechanisms. METHODS: PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before May 18, 2023. Review Manager 5.3 software was used to assess the data. RESULTS: We pooled 532 participants from six randomized controlled trials (RCTs). Compared to the placebo, the FcRn inhibitors were more efficacy in Myasthenia Gravis Activities of Daily Living (MG-ADL) (MD = - 1.69 [- 2.35, - 1.03], P < 0.00001), MG-ADL responder (RR = 2.01 [1.62, 2.48], P < 0.00001), Quantitative Myasthenia Gravis (QMG) (MD = - 2.45 [- 4.35, - 0.55], P = 0.01), Myasthenia Gravis Composite (MGC) (MD = - 2.97 [- 4.27, - 1.67], P < 0.00001), 15-item revised version of the Myasthenia Gravis Quality of Life (MGQoL15r) (MD = - 2.52 [- 3.54, - 1.50], P < 0.00001), without increasing the risk of safety. The subgroup analysis showed that efgartigimod was more effective than placebo in MG-ADL responders. Rozanolixizumab was more effective than the placebo except in QMG, and batoclimab was more effective than the placebo except in MG-ADL responder. Nipocalizumab did not show satisfactory efficacy in all outcomes. With the exception of rozanolixizumab, all drugs showed non-inferior safety profiles to placebo. CONCLUSION: FcRn inhibitors have good efficacy and safety in patients with MG. Among them, efgartigimod and nipocalimab were effective without causing an increased safety risk. Rozanolixizumab, despite its superior efficacy, caused an increased incidence of adverse events. Current evidence does not suggest that nipocalimab is effective in patients with MG.

The efficacy and safety of general anesthesia vs. conscious sedation for endovascular treatment in patients with acute ischemic stroke: a systematic review and meta-analysis.

Background: Endovascular thrombectomy (EVT) is an important treatment for patients with acute ischemic stroke (AIS). A number of studies have suggested that anesthesia type (conscious sedation vs. general anesthesia) during intra-arterial treatment for acute ischemic stroke has implications for patient outcomes. Methods: PubMed, EMBASE, Cochrane Library and clinicaltrials.gov were searched for randomized controlled trials (RCTs) that were performed to evaluate general anesthesia (GA) and conscious sedation (CS) up to May 30, 2023. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and mean difference (MD) were analyzed and calculated with a fixed effect model. Results: We pooled 930 patients from seven RCTs. We conducted a meta-analysis comparing the outcomes of GA and CS in the included trials. The rate of functional independence in the GA group was higher than that in the CS group (RR: 1.17, 95% CI: 1.00-1.35; P = 0.04; I2 = 16%). The GA group had a higher successful recanalization rate than the CS group (RR: 1.15, 95% CI: 1.08-1.22; P < 0.0001; I2 = 26%). The GA group had a higher pneumonia rate than the CS group (RR: 1.69, 95% CI: 1.22-2.34; P = 0.002; I2 = 26%). In addition, there was no significant difference between GA and CS with respect to the National Institutes of Health Stroke Scale (NIHSS) score at 24 h (P = 0.62), Modified Rankin Scale (mRS) score at 90 days (P = 0.25), intracerebral hemorrhage (P = 0.54), and mortality at 3 months (P = 0.61). Conclusion: GA demonstrated superiority over CS in achieving successful recanalization and functional independence at 3 months when performing EVT in AIS patients. However, it was also associated with a higher risk of pneumonia. Further studies, particularly those with long-term follow-ups, are necessary to identify precise strategies for selecting the appropriate anesthetic modality in EVT patients. Systematic review registration: INPLASY202370116.

The efficacy and safety of anti-Aß agents for delaying cognitive decline in Alzheimer's disease: a meta-analysis.

Background: This meta-analysis evaluates the efficacy and safety of amyloid-ß (Aß) targeted therapies for delaying cognitive deterioration in Alzheimer's disease (AD). Methods: PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before January 18, 2023. Results: We pooled 33,689 participants from 42 studies. The meta-analysis showed no difference between anti-Aß drugs and placebo in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and anti-Aß drugs were associated with a high risk of adverse events [ADAS-Cog: MDs = -0.08 (-0.32 to 0.15), p = 0.4785; AEs: RR = 1.07 (1.02 to 1.11), p = 0.0014]. Monoclonal antibodies outperformed the placebo in delaying cognitive deterioration as measured by ADAS-Cog, Clinical Dementia Rating-Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), without increasing the risk of adverse events [ADAS-Cog: MDs = -0.55 (-0.89 to 0.21), p = 0.001; CDR-SB: MDs = -0.19 (-0.29 to -0.10), p < 0.0001; MMSE: MDs = 0.19 (0.00 to 0.39), p = 0.05; ADCS-ADL: MDs = 1.26 (0.84 to 1.68), p < 0.00001]. Intravenous immunoglobulin and γ-secretase modulators (GSM) increased cognitive decline in CDR-SB [MDs = 0.45 (0.17 to 0.74), p = 0.002], but had acceptable safety profiles in AD patients. γ-secretase inhibitors (GSI) increased cognitive decline in ADAS-Cog, and also in MMSE and ADCS-ADL. BACE-1 inhibitors aggravated cognitive deterioration in the outcome of the Neuropsychiatric Inventory (NPI). GSI and BACE-1 inhibitors caused safety concerns. No evidence indicates active Aß immunotherapy, MPAC, or tramiprosate have effects on cognitive function and tramiprosate is associated with serious adverse events. Conclusion: Current evidence does not show that anti-Aß drugs have an effect on cognitive performance in AD patients. However, monoclonal antibodies can delay cognitive decline in AD. Development of other types of anti-Aß drugs should be cautious. Systematic Review Registration: PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42023391596.