Worsening after alemtuzumab

#MSresearch #Clinicspeak

Haghikia A, Dendrou CA, Schneider R, GrĂ¼ter T, Postert T, Matzke M, Stephanik H, Fugger L, Gold R. Severe B-cell-mediated CNS disease secondary to alemtuzumab therapy. Lancet Neurol. 2017;16: 104-106.

We have recently had reports suggesting that people taking alemtuzumab after fingolimod may be at increased risk of treatment failure. Bad news for alemtuzumab

In these case (two) reports presented the inference is that some people may not respond well. In this study the suggestion was made that alemtuzumab did not treat MS and instead generated a severe, antibody mediated CNS condition within a few months. 

Both pwMS responded to plasmaphersis (which is removing antibodies from the blood). Indicating that alemtuzumab had allowed the generation of autoreactive antibodies. We know that this happens, as alemtuzumab is associated with a variety of B cell mediated autoimmunities. Is this (1) augmentation of MS, (2) generating a new autoimmunity targeting the CNS, or (3) a fluke of disease reactivation? 

In both cases, they were treated with B cell depletion thereapy using rituximab. This does not cause immediate plasma cell depletion and disease was controlled.

I believe that B cell autoimmunity is an inherent problem of using alemtuzumab, due to its depletion characteristics (more on this later), but without more info, it is all speculation. However (2) is a possibility but this could be part of (1) also.

CoI: Currently non-relevant