Hauser S SL, Waubant W. Arnold DL, Vollmer T, et al for HERMES Trial Group. B Cell Depletion with rituximab in relapsing remitting multiple sclerosis. NEJM 2008; 358: 676-678
and editorial
McFarland HF. Focus on research: the B Cell -- old player, new position on the team. NEJM 2008; 358: 664-666.
The phase 2 trial of Rituxan (Rituximab, Biogen Idex and Genentech) in relapsing remitting multiple sclerosis showed a significant reduction of relapses and of MRI lesions, the primary outcome measure. It was a short trial (48 weeks) and not powered to show an effect on disability. There was a rapid reduction not only of contrast enhancing lesions on MRI but also total lesions, within 4 weeks. McFarland opines that the benefits of led to increased interest in the role of B cells in diseases thought to be mediated by T cells. Some patients may have antibody mediated complement destructive lesions and in others B cells may precede lesion development. However the rapidity of the response suggests another mechanism. Possibly, B cells are involved in antigen presentation to T cells and activation of T cell programming (cites Rock, 1984). They may contribute to T cell priming and lesion formation. Treated patients showed the subsequent development of naive rather than memory B cells.
Many trials have shown a reduction of MRI lesions but not clinical disease activity. Since antibodies maybe involved in repair mechanisms, clinical status of the patients will need to be closely monitored in the phase 3 trial. B cells may alos be important within lesions, as CXCL13 which regulated B cell migration in lymphoid tissue is found within plaques.
The study is a phase 2 trial, which means that unanswered questions include low frequency side effects, duration of oeffect, and effect on disability. The study involves only 104 patients.
Carnival of MS Bloggers and the launch of a unique and inclusive Global Multiple Sclerosis Community
ReplyDeleteHi,
I came across your blog via the Carnival Of MS Bloggers, I am Squiffy of Squiffy's House of Fun, on the list ;O)
You may be interested to hear about a new, unique and inclusive Global Multiple Sclerosis Community providing not only up to date MS News and Stories, but a place where those affected by Multiple Sclerosis can communicate with others affected by the disease, and the wider public, by means of Online Blogs, Discussion Forums and Net-based social interaction, which the Multiple Sclerosis Resource Centre launched onth March 6th in collaboration with cre8Buzz.
Why not come and have a look, there are already some established MS bloggers signed up, and maybe join in, it is a great way to promote your blogs etc.
http://www.cre8buzz.com/multiple_sclerosis
squiffs ;O)