No-evidence of disease activity (NEDA) means
- No Clinical Relapse
- No New Lesion activity
- No progression of EDSS
ProfG works some magic with Oreclizumab to make it better than any other chemical DMT.
What’s he done?
Ocrelizumab has become the first treatment for PPMS but there have been complaints that the trials was loaded with people with active disease and so it would respond to treatment as shown with the earlier rituximab studies. However, is this not learning from the past and adapting studies to show a positive effect.
In this study, they rebaseline the MRI and the NEDA rates increase from about 45-50% to closer to 75%.
Is this a fudge too? Again it is learning from biology.
It appears that once triggered disease activity is destined to occur and it is too late to stop it with DMT. So rather than comparing to when drugs are started you give it a few months to work. Then use this as a baseline.
I predict that thiis will become the norm from now on.
Havrdová E, Arnold DL, Bar-Or A, Comi G, Hartung HP, Kappos L, Lublin F, Selmaj K, Traboulsee A, Belachew S, Bennett I, Buffels R, Garren H, Han J, Julian L, Napieralski J, Hauser SL, Giovannoni G. No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a. Mult Scler J Exp Transl Clin. 2018 Mar 12;4(1):2055217318760642.
BACKGROUND: No evidence of disease activity (NEDA; defined as no 12-week confirmed disability progression, no protocol-defined relapses, no new/enlarging T2 lesions and no T1 gadolinium-enhancing lesions) using a fixed-study entry baseline is commonly used as a treatment outcome in multiple sclerosis (MS).
OBJECTIVE:The objective of this paper is to assess the effect of ocrelizumab on NEDA using re-baselining analysis, and the predictive value of NEDA status.
METHODS:NEDA was assessed in a modified intent-to-treat population (n = 1520) from the pooled OPERA I and OPERA II studies over various epochs in patients with relapsing MS receiving ocrelizumab (600 mg) or interferon beta-1a (IFN β-1a; 44 μg).
RESULTS: NEDA was increased with ocrelizumab vs IFN β-1a over 96 weeks by 75% (p < 0.001), from Week 0‒24 by 33% (p < 0.001) and from Week 24‒96 by 72% (p < 0.001). Among patients with disease activity during Weeks 0‒24, 66.4% vs 24.3% achieved NEDA during Weeks 24‒96 in the ocrelizumab and IFN β-1a groups (relative increase: 177%; p < 0.001).
CONCLUSION: Superior efficacy with ocrelizumab compared with IFN β-1a was consistently seen in maintaining NEDA status in all epochs evaluated. By contrast with IFN β-1a, the majority of patients with disease activity early in the study subsequently attained NEDA status with ocrelizumab.
OBJECTIVE:The objective of this paper is to assess the effect of ocrelizumab on NEDA using re-baselining analysis, and the predictive value of NEDA status.
METHODS:NEDA was assessed in a modified intent-to-treat population (n = 1520) from the pooled OPERA I and OPERA II studies over various epochs in patients with relapsing MS receiving ocrelizumab (600 mg) or interferon beta-1a (IFN β-1a; 44 μg).
RESULTS: NEDA was increased with ocrelizumab vs IFN β-1a over 96 weeks by 75% (p < 0.001), from Week 0‒24 by 33% (p < 0.001) and from Week 24‒96 by 72% (p < 0.001). Among patients with disease activity during Weeks 0‒24, 66.4% vs 24.3% achieved NEDA during Weeks 24‒96 in the ocrelizumab and IFN β-1a groups (relative increase: 177%; p < 0.001).
CONCLUSION: Superior efficacy with ocrelizumab compared with IFN β-1a was consistently seen in maintaining NEDA status in all epochs evaluated. By contrast with IFN β-1a, the majority of patients with disease activity early in the study subsequently attained NEDA status with ocrelizumab.
CoI : ProfG is a coauthor of this work.
I guess I should be happy as I take Ocrevus but I am not. These "top" neurology authors, surely all paid handsomely by Roche, sure hit a homerun with yet another neuroinflammatory study. I wonder how HSCT, Tysabri, rituximab or alemtuzumab would do against Ocrevus with re-baselining instead of using an ineffective CRAB drug, interferon, yet again.
I really wish all these "top" neurologists in the world would stop comparing any DMD to CRAB drugs, which have no effect on progression above placebo. They all know the CRAB drugs, despite their billions made by Pharma with their neurologists, have no effect above placebo on disease progression in MS.
Before these influential neurologists continue to pat each other on the back, I really wish they would start actively working on promoting the other 3/4 of the treatment pyramid but I guess this does not pay them as well. There are people suffering badly and by them continually promoting treatment of the neuroinflammatory model only, they are obstructing further meaningful treatments in neurodegeneration, remyelination and neurorestoration, which are sorely lacking.
Well said.
Whilst I do not diagree with you on this one and some of these authors will be in the alphabet neurologists a-j in the Coles paper.
The rebaselining is not against the CRABS but against itself so month 3 after ocrevus is month 0 in the rebaseline.
That they go againist a CRAB drug is not the fault of the neuros, although they perhaps do not stand up enough to say it is not ethical as they know the CRABS are not that effective, it is the pharma people who decide what actually gets done, the neuros can advise but cannot dictate.
The real problem is the ethical review panels it they got a spine and said no it would not happen. However, how many times do we see NIH trials go against placebo. So we should not put all the blame on pharma.
It's the same old names putting their names to these papers. I wonder how much each would get paid for each paper they put their name to. Prof G thinks it's ok to just declare a conflict of interest. I don't think that is the real point. People with MS have shorter life spans, more likely to be unemployed… yet the experts (who have made little impact on disability progression and still do not know the cause of disease) are doing very well financially from this disease. I suppose the money compensates them from not having the rewards of giving their patients their health back (like heart surgeons and oncologists).
"I wonder how much they get paid"…It's not really any of our business, but they will work to an hourly/daily rate just like any other profession doing a job. They don't work for free but neither does a mechanic sorting out a car.
"I suppose the money compensates…..for not having rewards"…I suspect that if you ask people who had alemtuzumab ten years ago they would not all be slagging the docs from Cambridge off. Many people have done very well and sing the praises of ProfCs. This will happen for some of the other potent MS treatments.
Oncology and cardiology has made big progress but if you ask about the amounts that have gone into research of either of these two conditions it dwarfs that spent on MS. In cancer the outocmes are clear and can be seen in a short amount of time. This is not the case for neurological problems
I agree with above posts but why have none of the neurologists replied ?
They are probably on holiday as its easter!
NEDA after twelve weeks? What a joke of an outcome. I was diagnosed with MS 18 years ago and I have often had periods much longer than 12 weeks when I had NEDA. I've also been on a highly active or moderately active DMD for the last 7 years. But now I'm using a wheelchair full-time and struggling with agonising neurological facial pain. I might well have showed as a success in this trial. When are neurologists going to face the fact that for lots of people MS takes at least a decade to show its horrible effects?
They can't do a longitudinal study on a med so new, but one wonders why they can't collate the data from Rituxan usage and extrapolate from there. . .oh right $. It's common knowledge we're all SPMS 90% of the time, my neuro could live a lavish lifestyle on his honorariums alone, yet the floor and chairs in his office are as threadbare and dirty as his heart. The analogy to a mechanic grunting away inside of a car doesn't quite follow although I think these UK doctors must care more because they will take time to answer blog posts.
"I think these UK doctors must care more because they will take time to answer blog posts."
Good point.
Although often responding MD's are the Mouse Doctors.
Will people in Great Britain who have paid for rituximab be moved onto Ocrelizumab when it is available?
I dont know
No-one pays for rituximab in Great Britain. We have a welfare state – those who earn pay taxes and the cost of medicines (and the cost of the health service) is paid out of these taxes.
No-one gets rituximab full stop. I've tried 🙁
Sorry to disagree with both of you, but I do know of someone in the UK who pays for rituximab.
I don't know whether the welfare state would actually pay for them to move to Ocrevus, they would have to meet the same criteria as everyone else will, it's not done on the basis of replacing drug for drug.
And I tried too, AM. 🙁
Bad luck JoH 🙁
Out of interest does the person pay for all costs of treatment or just the drug itself? Don't answer if you'd rather not.
NICE not sounding positive re ocrelizumab I hear, which probably means still negotiating….
Likewise, Annonie Mouse. 🙁
I believe the person paid for the cost of treatment too, but the drug was the major part of the cost.
According to the UK MS Society's news website, NICE has initially given a "no" for RRMS – so all our discussions may turn out to be academic…. and where that leaves pwPPMS – anyone's guess…
https://www.mssociety.org.uk/ms-news/2018/04/nice-says-initial-no-ocrelizumab-relapsing-ms