The continuous improvements of our understanding of the pathophysiological 
changes that occur in multiple sclerosis (MS) have translated into many novel 
therapeutic agents at different stages of development. These agents target more 
specifically the innate or the adaptive immune response. We will review agents 
available or under development that target the humoral pathways of the adaptive 
immune response. As such, humoral targeted immunotherapies that are being 
developed for MS are discussed herein: rituximab, ocrelizumab, and ofatumumab 
show promise as B-cell depleting agents. Other agents, such as atacicept were 
suspended during development in MS due to increased inflammatory activity versus 
the placebo. Although most agents were tested in relapsing-remitting forms of 
MS, rituximab and ocrelizumab have both been studied in progressive MS, whereas 
ocrelizumab only is currently moving forward in primary progressive MS trials. 
We provide an overview of agents available and under development that target the 
humoral response and include their mechanisms of action, safety profiles, and 
results of clinical trials.