ProfG has thrown the T and B curve ball by suggesting that brain atrophy data is better with the T and B depleters (Alemtuzumab and HSCT) than the relative B depleters (Ocrelizumab and cladribine).
This is an interesting observation and if correct it needs to be brought into the MS World View. This may point the finger at CD8 T cells as this subset deleted less than CD4 by cladribine and is dominant in MS lesions and are depleted by alemtuzumab and HSCT but not ocrelizumab
So as the Maven lands the first comment posted says “What about atrophy?”
The atrophy data in the CLARITY trial is admitedly not that great with a rate of about -0.56% brain loss a year (De Stefano et al. Mult Scler. 2018;24:222-226). If this is compared to years 1–5: −0.48%, −0.22%, −0.10%, −0.19%, −0.07% with alemtuzumab in the CARE-MSI (Havrdova E et al. Neurology. 2017;89:1107-1116). After the first year it doesn’t look that great. Normal aging is about 0.1-0.2% brain loss a year.
However, I have said previously that the people in the CLARITY trial had MS for on average 9 years verses only 2 years in the CARE MS-I trial. It is well known that in the first year of many DMT there is seeming shrinkage because the loss of inflammation, leading to loss of swelling.
So I went back to the ORACLE study where people with first symptom was given the cladribine tablets where the mean duration of disease before treatment was 0.2 years. There was no data in the paper that I could remember.
However, when I had a look in the (unpublished..well sort of) supplementary trial data. The licenced 3.5mg/kg dose was -0.48% at years one and do the maths -0.2% at year 2. If you look at the higher dose it is -0.1% at year 2. Admittedly the year 1 and year 2 groups are not matched and the data needs to be properly re-analysed
However, my thesis that they all work the same is now still standing and the atrophy data looks comparable to me. Head to head studies needed but probably won’t happen.