You, Me and NEDA in MS
You may have heard or read the term NEDA (pronounced NEED-AH) in Multiple Sclerosis news in the past few months and wondered just what is NEDA and how does it apply to us? NEDA is an acronym for No Evidence of Disease Activity and sounds like the perfect goal to me.
I recently read the report Evaluation of No Evidence of Disease Activity in a 7-Year Longitudinal Multiple Sclerosis Cohort, published online for the Journal of American Medical Association (JAMA) Neurology, and saw the negative numbers of people sustaining NEDA over a long period of time and found the news discouraging. But it gnawed at me that I was missing something because there are a number of researchers looking at this topic and I sensed an underlying enthusiasm for NEDA. I reached out to my MSologist – Dr. Aaron Boster, OhioHealth Neurological Physicians – for an explanation of just what NEDA means in our long term care.
In a lengthy chat he covered again with me a number of points that most of us already know, including:
- Very few of us will remain disease activity free because that just isn’t how MS and our disease modifying therapy drugs work. We are fortunate to have the drugs, but we can still anticipate relapses or worse, they won’t work for us at all and it is not unusual that our disease modifying therapy (DMT) might need to be adjusted/changed.
- There is a shortage of what we might call MSologists, neurologists who specialize in Multiple Sclerosis. The majority of people receiving MS treatment do so with general neurologists, who may also treat people with Parkinson’s Disease, Stroke, Epilepsy and a host of other neurological disorders. The MSologist is a fairly rare breed with specialized training in MS and they have a great interest in sharing their expertise with other physicians.
The lack of MS specialists is part of the impetus of the NEDA movement, according to Dr. Boster, and he says many people are diagnosed with MS, given a disease modifying therapy drug, and then have very little follow through with their general neurologist. A few years later, if they’re lucky, they are still not doing so bad. But for many people, this approach of let’s treat the MS and see what happens is hazardous to our health and that’s where the importance of NEDA comes in.
There is a move to shift the thinking about our treatment goals and it is no longer enough to just be thinking about getting us on a DMT and meandering and hoping for the best, but now we know we must also monitor how we react to a disease modifying therapy and making adjustments in our treatment plan. This is where NEDA (No Evidence of Disease Activity) as our goal comes in for the long haul.
And what is this NEDA the clinicians are looking for? Disease activity in this case could be one of at least three different markers- one attack/relapse, sustained/increased disability, or one new or enlarging lesion seen on MRI exam.
If you’ve read any of my other articles that include my talks with Dr. Boster, you already know he loves to use home-spun analogies to explain difficult concepts. NEDA is no exception and he offered basketball championships as an example to explain why it is important. I am taking the liberty and changing the sport to pro football because it makes more sense to me ….
NEDA is the equal to what happens at the beginning of the season – every team has the goal of making it to the Super Bowl. In MS care, this winning goal would be NEDA and the patient living a fairly normal life.
As the season plays on, some of the 32 teams win and some lose. The losing teams often switch up their personnel, including the quarterback and sometimes even the coach. In the case of MS, the people on the winning therapies that keep the disease quiet, keep moving forward. The folks who are on the losing side- and we know not all of us respond to the same treatments - may switch therapies or even doctors.
In the case of people who are not seeing an MS specialist, they may assume there is nothing else out there for them and they reluctantly accept losing the battle with MS. A part of thinking so much about NEDA is making other clinicians and patients aware that just settling for inferior results is not the only option they might have.
Toward the end of the season, 12 of the starting 32 football teams are still playing – meaning 37.5% are still having success, but over 60% have failed and they take the time to reshape their team and game plan. Eventually four teams make it to their division championships and two move on to play for the Super Bowl title. The football competition moves even further, advancing to the Super Bowl. But eventually, team after team is knocked out with a loss.
There are a lot of teams that begin the quest for the prized Super Bowl ring, but only 3.125% of the original 32 teams make it to that lofty goal. Unfortunately, the same is true with MS treatment, and for now we know 100% of us will not achieve NEDA over the long haul. Dr. Boster points out that nataluzimab (Tysabri), the most potent DMT available for our use right now in the US and also my drug, has shown NEDA of 37%, so it is encouraging that the new drugs are increasing our odds.
In Evaluation of No Evidence of Disease Activity in a 7-Year Longitudinal Multiple Sclerosis Cohort, researchers from Boston’s Partners MS Center, Brigham and Women’s Hospital and the Biostatistics Center, Massachusetts General Hospital took an in depth look at a large cohort of people with MS for NEDA over a longer period of time.
There is a group of people treated at Partners MS Center who have been included in a study of patients named the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB) cohort study, This is a group of people who have been routinely followed with clinical exams and MRI studies over a long period of time, many since their initial diagnosis of either Clinically Isolated Syndrome (CIS) or Relapsing Remitting MS (RRMS). From CLIMB, 219 people were identified who had been diagnosed for 7 years or longer and had comprehensive clinical and test records.
The results of studying their MRI’s, Expanded Disability Status Scale (EDSS) numbers, clinical exams and other measures showed at the one year mark 46% of the group had NEDA. That leaves 54% of the cohort showing some form of change in their MS measures. After seven years, the number of people who still had NEDA drops to just 7.9%. That means 92% of the group showed some form of disease activity.
This number is discouraging but not a surprise – with the current treatments we have for MS, there is a continuing change in our condition for most of us. Perhaps though, these drugs are slowing the progression and that is an important factor to consider that can’t be measured – how much worse would our MS be if we didn’t take these drugs? It should also be noted that this group of people did not have the advantage of the newer DMTs, including the oral therapies, and these numbers are based primarily the early injectable therapies of interferon (Betaseron, Rebif, Avonex) and glatiramer acetate (Copaxone).
NEDA and this study is discussed further on the JAMA Neurology page – I hope you will listen to their explanation by clicking on the link on the right side of the page (you may have to scroll down on your screen) marked Related Multimedia – Author Interview .
The manufacturers of the oral MS disease modifying drugs are also lining up to discuss NEDA – recently released is a study that compares three oral treatments, but their comparison is over a much shorter duration of time than the seven years in the above study. No evidence of disease activity: indirect comparisons of oral therapies for the treatment of relapsing-remitting multiple sclerosis compares NEDA from the phase III clinical trial results of fingolimod (Gilenya), dimethyl fumarate (Tecfidera) and teriflunomide (Aubagio). The complete study results are available free online for readers who might be interested in what they might show. I won’t go into details here because again, the length of time for the comparison seems too short of a period and too few participants, and this look at NEDA might be prompted by the promotional needs of the drug company that showed superiority.
So what does this mean for all of us who have MS? It would be great if I could tell you that brand XYZ of a drug has the best chance for NEDA. There is discussion among the neurologists as to how aggressive of a treatment they should offer to all of us – is the risk of stronger drugs worth the benefits of NEDA? If so, how long might those benefits hold off our MS until it again breaks through, if at all?
It does appear that the early NEDA marks will be a predictor of how aggressive/severe our MS might be. More significantly, according to Dr. Boster, what they are now learning through NEDA is the positive predictive rates for our disease progression. He says that at one year they now have a 72% rate and at 2 years, it increases to a 78% predictive value of understanding how our MS is going to look in the long term. This doesn’t necessarily mean it is great news, but they can see the pattern of progression for most of us and how it will probably fit into our individual case. No disease activity in the first year or two, is a very good sign for our long term MS pattern. He is hopeful that the predictive value will increase to at least 80% and believes every patient should discuss the expectations of NEDA with their own neurologist as it relates to their care.
This is about redefining how we think about treatment, and now that disease modifying therapies are more widely available, we can expect the new goals set by our doctors and the drug makers to include NEDA. Ultimately, though, the best no evidence of disease activity (NEDA) is going to come when the cure for MS is found. Until then, unlike the Super Bowl, fortunately in MS we can have more than one person achieve the team’s goal of NEDA and I hope you are one of them.
Wishing you well,
Do you have a fear of needles and take medication that requires injection?