Comparative the efficacy and safety of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in patients with Alzheimer's disease: a systematic review and network meta-analysis of randomized controlled trials

Objective : The aim of this study was to compare the efficacy and safety of anti-tau protein monoclonal antibodies for Alzheimer's disease (AD). By investigating the effects of monoclonal antibodies on cognitive function, disease progression, and overall quality of life in patients with AD, which can provide valuable insights into their potential as a therapeutic option for this devastating neurodegenerative disorder. Methods : The randomized controlled trials (RCTs) of Gosuranemab, Semorinemab, Tilavonemab and Zagotenemab in the treatment of AD were searched in database of PubMed, Embase, Web of Science and Cochrane Library, up to May 2024. The control group included placebo. The efficacy indicators were change in the Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) from baseline until the time of efficacy observation. The statistical analysis was performed by Stata14 and RevMan5.4. Data processing, network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots and funnel plots were generated. Mean differences (MD) and 95% confidence interval (95%CI) as effect sizes to analyze continuous variables. Results : This study included six RCTs with 2193 patients. Semorinemab were more effective than placebo in MMSE and ADAS-Cog scores (MDs ranging between 0.52 and 3.21; MDs ranging between 0.17 and 3.30). Placebo showed relatively good efficacy according to SUCRA ranking on change in CDR-SB and ADCS-ADL scores(75.7% and 79.5%). Tilavonemab and Semorinemab exhibited efficacy similar to that of a placebo in the analysis of the two indicators. Tilavonemab showed a lower incidence of AE, SAE, fall, and urinary tract infections than placebo, and the differences were statistically significant. Most safety analysis results showed no statistical difference. Conclusions : Based on the results of this study, Semorinemab and Tilavonemab were recommended treatment options with relatively good efficacy and safety. These encouraging outcomes suggest that anti-tau protein monoclonal antibodies hold considerable potential as a viable therapeutic option for managing AD. Further exploration and clinical validation are warranted to fully elucidate the long-term effects and optimize treatment protocols in this evolving therapeutic landscape.