Efficacy and safety of anti-tau drugs for Alzheimer’s disease: A systematic review and network meta-analysis

Objective To evaluate and compare the effects of different anti-tau drugs on clinical and biological outcomes in patients with Alzheimer’s disease (AD). Methods PubMed, Cochrane Library, and Embase databases were searched for identifying randomized, controlled clinical trials from inception to December 2025. Results Twelve high-quality studies with 11 drugs were evaluated. Systematic meta-analysis did not demonstrate significant efficacy of anti-tau drugs in preventing cognitive and functional declines or clearance of tau deposition on PET. However, effects in reducing levels of p-tau (SMD=-0.48, 95% CI: -0.73 to -0.22, P < 0.01) and t-tau (SMD=-0.69, 95% CI: -0.94 to -0.45, P < 0.01) in the cerebrospinal fluid were observed. Network analysis revealed that MAPT Rx and nicotinamide ranked highest for improving cognitive function, and gosuranemab ranked highest for tau biomarker changes. Conclusion The current findings highlight the disease-modifying potential of anti-tau therapies for AD, although clinical benefit is limited. The observed reductions in CSF tau biomarkers and the favourable safety profile of current anti-tau therapies suggest promising therapeutic potential for the treatment of AD. However, the clinical value of anti-tau therapies should be confirmed in adequately powered phase III trials with biomarker-enriched populations.