Taking progressive biology seriously in the time of B-cells and BTK.

The successful landscape of relapsing remitting multiple sclerosis (RRMS) treatments has revolutionized our conceptualization of the disease. This led to a shifting interest towards finding ways of stopping neurodegeneration in progressive MS. The past decade brought us lots of new definitions, such as compartmentalized inflammation, progression free of relapsing activity and the proposal of MS as a disease continuum. It also brought novel therapeutic candidates, the Bruton´s Tyrosine Kinase inhibitors. Unfortunately, the results (reported and announced) of clinical trials in progressive MS have been underwhelming. A recurring theme that may explain the current state of the field is the handling of classical inflammatory "relapsing biology" in progressive MS populations. Although co-pathology of these processes along with neurodegeneration is expected, the time is ripe to take progressive biology seriously.