Lymphopaenia and opportunistic infections; the new marketing battleground in MS. #ClinicSpeak #Neurospeak #MSBlog
There is has been a rather large response to my post yesterday on opportunistic infections in alemtuzumabers. A large number of you have been asking me about opportunistic infections on other DMTs, in particular fingolimod and DMF. Fingolimod mainly suppresses lymphocyte responses and can't be derisked; i.e. a fingolimod works by causing a lymphopaenia. In addition, most of the opportunistic infections on fingolimod have occurred with lymphocytes above 200/mm3, the EMA's recommended cut-off for dose interruption.
The table below summarises the types of infections to expect with the nature of the immunosuppression. DMF (dimethyl fumarate) does cause lymphopaenia, in 5-15% of treated MSers. However, we derisk DMF-induced lymphopaenia by switching patients onto another DMT. At Barts-MS our cut-off is 800/mm3, but other centres use 500/mm3.
Cladribine is similar to alemtuzumab in its mode of action, but you don't get a profound depletion of lymphocytes. Cladribine also leave the innate cells relatively intact, therefore Listeria is unlikely to be a problem with cladribine. In addition, we adjust the dose of cladribine to prevent grade 4 lymphopaenia (<200/mm3).
Daclizumab (anti-CD25) is an outlier in that it does not cause a global lymphopaenia and as a monotherapy has not been associated with opportunistic infections. Lymphocyte counts drop by about 10-15% on daclizumab, which rarely takes the total counts below normal. The main issue with daclizumab is that common infections may be more serious. However, these can be treated earlier and more actively.
Ocrelizumab (anti-CD20) only depletes B-cells; in the short-term this strategy looks clean. However, with time B-cell depletion may affect antibody responses (long-lived plasma cells don't live forever) and then we would expect to see infections occurring with encapsulated bacteria (streptococci, meningococci, etc.).
It is clear that lymphopaenia and opportunistic infections are becoming the new battle ground between the DMTs. Safety, in particular long-term safety is going to be a major differentiator between the DMTs.
CoI: multiple
There is has been a rather large response to my post yesterday on opportunistic infections in alemtuzumabers. A large number of you have been asking me about opportunistic infections on other DMTs, in particular fingolimod and DMF. Fingolimod mainly suppresses lymphocyte responses and can't be derisked; i.e. a fingolimod works by causing a lymphopaenia. In addition, most of the opportunistic infections on fingolimod have occurred with lymphocytes above 200/mm3, the EMA's recommended cut-off for dose interruption.
The table below summarises the types of infections to expect with the nature of the immunosuppression. DMF (dimethyl fumarate) does cause lymphopaenia, in 5-15% of treated MSers. However, we derisk DMF-induced lymphopaenia by switching patients onto another DMT. At Barts-MS our cut-off is 800/mm3, but other centres use 500/mm3.
Cladribine is similar to alemtuzumab in its mode of action, but you don't get a profound depletion of lymphocytes. Cladribine also leave the innate cells relatively intact, therefore Listeria is unlikely to be a problem with cladribine. In addition, we adjust the dose of cladribine to prevent grade 4 lymphopaenia (<200/mm3).
Daclizumab (anti-CD25) is an outlier in that it does not cause a global lymphopaenia and as a monotherapy has not been associated with opportunistic infections. Lymphocyte counts drop by about 10-15% on daclizumab, which rarely takes the total counts below normal. The main issue with daclizumab is that common infections may be more serious. However, these can be treated earlier and more actively.
Ocrelizumab (anti-CD20) only depletes B-cells; in the short-term this strategy looks clean. However, with time B-cell depletion may affect antibody responses (long-lived plasma cells don't live forever) and then we would expect to see infections occurring with encapsulated bacteria (streptococci, meningococci, etc.).
It is clear that lymphopaenia and opportunistic infections are becoming the new battle ground between the DMTs. Safety, in particular long-term safety is going to be a major differentiator between the DMTs.