Role of C5 inhibitors in neuromyelitis optica spectrum disorders with seropositive anti-aquaporin-4 antibody: A systematic review and meta-analysis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by relapses of inflammation and demyelination primarily affecting the optic nerve and the spinal cord. C5 complement inhibition is an effective therapeutic approach in the treatment of NMOSD. In this systematic review and meta-analysis, we aimed to determine the role of C5 inhibitors in the treatment of patients with seropositive anti-aquaporin-4 antibody (AQP4+IgG) NMOSD. METHODS: This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Relevant articles were systematically searched through Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases until October 6th, 2023. We included randomized clinical trials (RCTs) that investigated the treatment with C5 inhibitors compared to placebo in patients with seropositive NMOSD. The primary endpoint was the rates of first adjudicated relapse. Secondary endpoints included different disability and quality of life measures. The random-effects model was used for all statistical analyses. RESULTS: Two RCTs with a total of 201 patients were included. C5 inhibitors demonstrated significant reduction of first adjudicated relapse (risk ratio (RR) = 0.05, 95 % CI 0.01-0.15) and Hauser Ambulation Index (HAI) (mean difference (MD): -0.79, 95 % CI -1.27 to -0.31). There was no significant difference between the two groups in Expanded Disability Status Scale (EDSS) (MD -0.23, 95 % CI -0.54-0.08). C5 inhibitors significantly improved the mean change in EQ-5D index (MD 0.08, 95 % CI 0.01-0.14; P = 0.02); however, no significant difference was shown in the mean change in EQ-5D VAS (MD 3.79, 95 % CI -1.61 to 9.19; P = 0.17). Safety measures were comparable between C5 inhibitors and placebo. CONCLUSION: NMOSD Patients with AQP4+IgG receiving C5 inhibitors have lower rate of relapses and improved levels of disability and quality of life. Real-world studies are warranted to establish the long-term safety of C5 inhibitors.

Influenza vaccine effect on risk of stroke occurrence: a systematic review and meta-analysis.

Background: Stroke is a significant global cause of mortality and long-term disability, potentially influenced by infections that heighten systemic inflammation and thrombotic events. The full impact of influenza vaccination on stroke remains uncertain. This systematic review and meta-analysis aimed to investigate the association between influenza immunization and stroke incidence. Methods: We searched for randomized controlled trials (RCTs), case-control, and cohort studies published in PubMed/Medline, Cochrane-Central-Register-of-Controlled-Trials (CENTRAL), and Embase until 5 December 2022, and identified articles investigating the effect of influenza vaccine on stroke occurrence. All articles were screened by two independent reviewers. We performed a meta-analysis to investigate the risk of stroke occurrence in vaccinated vs. unvaccinated individuals. The random-effects model was used in all statistical analyses. Results: Among the 26 articles meeting our criteria, 10 were retrospective cohort studies, 9 were case-control studies, 3 were prospective cohort studies, 3 were RCTs and 1 case-series. Overall, the studies showed a significant decrease in the risk of stroke incidence/hospitalization among vaccinated patients (OR = 0.81, 95% CI [0.77-0.86], p = 0.00001). Furthermore, studies showed flu vaccine decreases the occurrence of mortality among stroke patients (OR = 0.50, 95% CI [0.37-0.68], p = 0.00001). Sub-group analysis revealed significant protective effect for patients with specific comorbidities including atrial fibrillation (OR = 0.68, 95% CI [0.57-0.81], p = 0.0001), diabetes (OR = 0.76, 95% CI [0.66-0.87], p = 0.0001), Chronic obstructive pulmonary disease (OR = 0.70, 95% CI [0.61-0.81], p = 0.00001), and hypertension (OR = 0.76, 95% CI [0.70-83], p = 0.00001). Conclusion: The current meta-analysis further supports prior findings that influenza vaccination reduces stroke risk, particularly in patients with comorbidities. Guidelines should promote vaccination for at-risk individuals.