I've been trying evaluate the risks and benefits of rituxan and found these items of interest below.
Given that rituxan has such a devastating effect on both B and T cells, I am actually surprised that only 23 cases (and 2 deaths) have been reported from PML. Rituxan seems to be rather like Cytoxin and Novantrone in nuking the entire system. At least Tysabri appears to be a more discrete weapon, acting to inhibits interactions between alpha4-integrin and its ligands (presumably stopping the migration of leucocytes to sites of inflammation within the CNS--if I understand it correctly).
I've read different estimates of PML morbidity--from 90% down to 50% die; the rest have permanent neurological damages. Treatment aims at reconstituting the immune system--discontinuing the drug, perhaps using plasma pharesis. But, no effective drug exists.
How is it that Tysabri was suspended temporarily and now strictly limited to RRMS, while rituxan can have so many cases of PML and remain in such good repute?
In addition to the reports about rituxan collected at
http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1394
you might check out
Olaf Stüve, MD; Sabine Cepok, PhD; Birte Elias, MD; Andreas Saleh, MD; Hans-Peter Hartung, MD; Bernhard Hemmer, MD; Bernd C. Kieseier, MD, "Clinical Stabilization and Effective B-Lymphocyte Depletion in the Cerebrospinal Fluid and Peripheral Blood of a Patient With Fulminant Relapsing-Remitting Multiple Sclerosis," ARCH NEUROL 62 (OCT 2005): 1620-1623. WWW.ARCHNEUROL.COM
Nancy L. Monson, PhD; Petra D. Cravens, PhD; Elliot M. Frohman, MD, PhD;
Kathleen Hawker, MD; Michael K. Racke, MD, "Effect of Rituximab on the Peripheral Blood and Cerebrospinal Fluid B Cells in Patients with Primary Progressive Multiple Sclerosis," ARCH NEUROL 62 (FEB 2005): 258-264. WWW.ARCHNEUROL.COM
E Janas,* R Priest,* J I Wilde,† J H White,† and R Malhotra, "Rituxan (anti-CD20 antibody)-induced translocation of CD20 into lipid rafts is crucial for calcium influx and apoptosis,” Clin Exp Immunol 139.3 (March, 2005): 439–446 at
http://www.pubmedcentral.nih.gov/articl ... id=1809325
VERY HELPFUL is the PowerPoint presentation by
Andrew Sylvester, M.D., “Rituxamab (Rituxan) and Multiple Sclerosis” at
Sylvester offers charts showing how drastically both B cells and T cells are depleted, which I am unable to replicate here, unfortunately. It's sobering.
In short, is it worth taking this drug when its effect on B and T cells is so utterly destructive? What is left of the immune system? Maybe someone can explain how it is possible to live in such a state of compromise?