Your thoughts on the NEDA principle
Posted: Fri Feb 28, 2014 10:32 pm
NEDA, or "no evidence of disease activity" is the idea that the goal of treatment in relapsing multiple sclerosis should be as follows:
1) No clinical relapses
2) No new or worsening neurological exam findings
3) No new T2 bright MRI lesions
4) No enlarging T2 bright MRI lesions
5) No gadolinium enhancing MRI lesions
In other words, no evidence of any multiple sclerosis activity whatsoever by currently available means of detection. Another way to say this would be that the goal is to achieve both clinical and radiologic remission.
This is endorsed by the mouse doctor blog: http://multiple-sclerosis-research.blogspot.com/
They have some interest in doing a clinical trial on the subject
The idea is that you escalate therapy until NEDA is achieved.
For example:
You are a 22 year old female. You have left optic neuritis and retrospectively give a history of double vision 1 year earlier consistent with a likely brainstem demyelinating attack. MRI scans and spinal tap are consistent with a diagnosis of multiple sclerosis.
you are started on avonex. 6 months later, you developed numbness in the right leg and a banding sensation around the abdomen. You are diagnosed with a multiple sclerosis exacerbation (transverse myelitis), given IV solumedrol, and switched to tysabri.
In the following year, you have no clinical relapses, and screening MRI reveals no new lesions since the last relapse, so tysabri is continued as long as it can be tolerated with reasonable safety.
This would be an example of treating towards NEDA. Of course, avonex is unlikely to achieve NEDA in most MSers, so you may start with a more effective agent.
The justification of such an approach could be based on the following assumptions...
1) In the very long run, the natural history prognosis is poor. For instance, with no treatment, the 22 year old in this example probably has a fairly low likelihood of significant disability at age 30 but a fairly high likelihood of at least some degree of disability at age 60
2) The side effects of even second line therapies are minimal in risk compared to the risk of disability from MS in the long run
3) Early prevention of relapses and MRI lesion accumulation has an effect on time to secondary progressive MS or course of secondary progressive MS. In other words, achieving NEDA has long term therapeutic benefits, not mere benefits in preventing relapses which may recover anyways.
I think #3 is the most in question out of these assumptions.
Here are some of the potential pitfalls
1) In the future, much more effective and safer treatment of both progressive and relapsing MS may be developed, so by escalating therapy early, you may be taking unnecessary risk of side effects
2) Some individuals with MS will have some evidence of disease activity but will never acquire any disability and will not develop progressive MS (in other words, they will prove to have "benign MS"). By striving for NEDA, you risk treating yourself unnecessarily when you actually have benign MS.
3) There is no proof that achieving NEDA has any long term benefits. It may be that SPMS cannot be prevented or delayed with current therapies if it is predestined to occur.
4) Some aggressive therapies such as cytoxan/rituxan/alemtuzumab/novantrone have long term immunosuppressive effects
5) Newer second line DMTs such as tysabri and lemtrada may have long term deleterious effects which are not yet known.
6) There is clinical evidence from the interferon trials that mild lesion progression is often associated with being an "interferon responder"...at least in the short run.
What are your thoughts on the NEDA principle?
1) No clinical relapses
2) No new or worsening neurological exam findings
3) No new T2 bright MRI lesions
4) No enlarging T2 bright MRI lesions
5) No gadolinium enhancing MRI lesions
In other words, no evidence of any multiple sclerosis activity whatsoever by currently available means of detection. Another way to say this would be that the goal is to achieve both clinical and radiologic remission.
This is endorsed by the mouse doctor blog: http://multiple-sclerosis-research.blogspot.com/
They have some interest in doing a clinical trial on the subject
The idea is that you escalate therapy until NEDA is achieved.
For example:
You are a 22 year old female. You have left optic neuritis and retrospectively give a history of double vision 1 year earlier consistent with a likely brainstem demyelinating attack. MRI scans and spinal tap are consistent with a diagnosis of multiple sclerosis.
you are started on avonex. 6 months later, you developed numbness in the right leg and a banding sensation around the abdomen. You are diagnosed with a multiple sclerosis exacerbation (transverse myelitis), given IV solumedrol, and switched to tysabri.
In the following year, you have no clinical relapses, and screening MRI reveals no new lesions since the last relapse, so tysabri is continued as long as it can be tolerated with reasonable safety.
This would be an example of treating towards NEDA. Of course, avonex is unlikely to achieve NEDA in most MSers, so you may start with a more effective agent.
The justification of such an approach could be based on the following assumptions...
1) In the very long run, the natural history prognosis is poor. For instance, with no treatment, the 22 year old in this example probably has a fairly low likelihood of significant disability at age 30 but a fairly high likelihood of at least some degree of disability at age 60
2) The side effects of even second line therapies are minimal in risk compared to the risk of disability from MS in the long run
3) Early prevention of relapses and MRI lesion accumulation has an effect on time to secondary progressive MS or course of secondary progressive MS. In other words, achieving NEDA has long term therapeutic benefits, not mere benefits in preventing relapses which may recover anyways.
I think #3 is the most in question out of these assumptions.
Here are some of the potential pitfalls
1) In the future, much more effective and safer treatment of both progressive and relapsing MS may be developed, so by escalating therapy early, you may be taking unnecessary risk of side effects
2) Some individuals with MS will have some evidence of disease activity but will never acquire any disability and will not develop progressive MS (in other words, they will prove to have "benign MS"). By striving for NEDA, you risk treating yourself unnecessarily when you actually have benign MS.
3) There is no proof that achieving NEDA has any long term benefits. It may be that SPMS cannot be prevented or delayed with current therapies if it is predestined to occur.
4) Some aggressive therapies such as cytoxan/rituxan/alemtuzumab/novantrone have long term immunosuppressive effects
5) Newer second line DMTs such as tysabri and lemtrada may have long term deleterious effects which are not yet known.
6) There is clinical evidence from the interferon trials that mild lesion progression is often associated with being an "interferon responder"...at least in the short run.
What are your thoughts on the NEDA principle?