Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial
Neurology · 2015
tolerability of subcutaneous etanercept in patients with Alzheimer disease (AD) dementia.Although it was not their primary outcome, the authors hypothesized that etanercept could decrease systemic inflammation and result in cognitive benefits.Butchart et al. previously observed that baseline increased inflammatory marker levels were associated with more rapid decline in cognitive functions in patients with AD dementia. 2,3However, the levels of inflammatory markers in the current study are relatively low in comparison with those reported in their previous studies.Tumor necrosis factor range was 1.8-3.2pg/mL in the current study, while it was .3.27 pg/mL in the highest 2 quartiles in the previous study.In addition, interleukin (IL)-6 range was 0.5-1.5 pg/mL in the current study, while it was .2.8 pg/mL in the group with higher IL-6 in the previous study.Absence of low-grade systemic inflammation in the baseline visit may have attenuated a potentially beneficial effect of etanercept on cognitive functions in this study.Finally, the C-reactive protein (CRP) levels may be incorrect: they seem very high at 1.8 mg/mL and may actually have been 1.8 mg/mL.Studying subjects with higher baseline levels of inflammatory markers in further studies might provide valuable information.