Ziemssen T, Thomas K. Alemtuzumab in the long-term treatment of relapsing-remitting multiple sclerosis: an update on the clinical trial evidence and data from the real world. Ther Adv Neurol Disord. 2017;10:343-359
Alemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS), given as two annual courses on five consecutive days at baseline and on three consecutive days 12 months later. Here we provide an update on the long-term efficacy and safety of alemtuzumab in RRMS, including real-world experience, and advances in our understanding of its mechanism of action. Recent data from the phase II/III extension study have demonstrated that alemtuzumab reduces relapse rates, disability worsening, and the rate of brain volume loss over the long term, with many patients achieving no evidence of disease activity. In high proportions of patients, pre-existing disability remained stable or improved. Alemtuzumab is associated with a consistent safety profile over the long term, with no new safety signals emerging and the overall annual incidence of reported adverse events decreasing after the first year on treatment. Acyclovir prophylaxis reduces herpetic infections, and monitoring has been shown to mitigate the risk of autoimmune adverse events, allowing early detection and overall effective management. Data from clinical practice and ongoing observational studies are providing additional information on the real-world use of alemtuzumab. Recent evidence on the mechanism of action of alemtuzumab indicates that in addition to its previously known effects of inducing depletion and repopulation of T and B lymphocytes, it also results in a relative increase of cells with memory and regulatory phenotypes and a decrease in cells with a proinflammatory signature, and may further promote an immunoregulatory environment through an impact on other innate immune cells (e.g. dendritic cells) that play a role in MS. These effects may allow preservation of innate immunity and immunosurveillance. Together, these lines of evidence help explain the durable clinical efficacy of alemtuzumab, in the absence of continuous treatment, in patients with RRMS.
This is a review and we don't report of reviews but it is perhaps good that you can get an alternative view. If you can get access to this.
However I have been spending the day getting my poster ready for ECTRIMS 2017 and so was happy to see the state of play,
but....reading through this makes me feel that I am am living in an alternative universe:-(.
Apparently there are "no new safety signals" emerging so best not give a plug for the ECTRIMS poster that shows alemtuzumab can stop working
P1231. C. Eggers, K. Akgün, T. Hofer, M. Egger, T. Ziemssen
Abrogation of the lymphocyte depleting action of Alemtuzumab by neutralizing antibodies - a case report.
Apparently there is "recent evidence on the mechanism of action of alemtuzumab" so I thought great...our ideas are gaining some traction....but then the depression sets in.
So in addition to the mechanism of inducing depletion and repopulation of T and B lymphocytes ,we get a result in a relative increase of cells with memory and regulatory phenotypes...yeah that's T cells.
I guess memory B are not on the radar yet.
So the 30,000 cells per millilitre going down to 2 is still an increase in the minds of my peers?. Maybe that the 2 Treg cells are now controlling the 1 surviving CD4 T cell is the relative cell increase we need.
The new mechanism is a expansion of NKCD56 high, so it works like daclizumab too?
Have a read of this and tell me what you think.