Q&A 53 - more on tolebrutinib and BTKIs

What does tolebrutinib teach us about the differences between progressive and relapsing biology?

Question

I am a neuroimmunology fellow. Please share your perspective on tolebrutinib.

I am perplexed by the way this drug has seemingly separated relapse biology from progressive biology -- it reduces progression in BOTH relapsing people and non-relapsing people, but doesn't seem to significantly impact relapsing disease. 

What does this teach us about the differences between progressive and relapsing biology? You've mentioned before that you think the REAL MS is progression and that relapses might be something else, something independent. However, we have evidence that all people with MS have some elements of both. Relapsing people have evidence of subclinical disease progression. People who go on to develop progressive MS have pre-symptomatic evidence of focal, inflammatory MRI lesions that have come and gone (Correale et al. Benign multiple sclerosis: does it exist? Curr Neurol Neurosci Rep. 2012). 

Any additional thoughts would be so appreciated. 

Thanks for your time. 

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Prof G’s answer

In addition to answering these questions, I will discuss the evolution of the focal MS lesion and how Tolebrutinib and other BTK inhibitors (BTKIs) may impact it. 

Please note these question are research-related, hence them being labelled under MS-Selfie Research.