Many of my colleagues have criticised and reprimanded me for being over-enthusiastic in stating that immunosuppressive MS DMTs are relatively safe for pwMS if they happen to develop COVID-19 whilst on treatment. However, the issue has been asymmetry of knowledge. I have known that patients on DMTs who get COVID-19 are doing well. This is based on knowledge acquired from multiple sources albeit confidentially. I have been trying to encourage my colleagues to put this information into the public domain, but clearly it is not happening soon enough. The delays in getting this information out to you the MS community has been far too slow. Do you agree? The good news is there are now platforms to speed up the dissemination of data; let’s hope it changes behaviour.
At last, the Italian COVID-19 and MS pilot data has been published in a peer-reviewed journal. They report on the first 232 patients with MS who developed COVID-19. I actually commented on this data on the blog on the 10th April and it was only published yesterday. There is nothing new to report. This delay is simply unacceptable as HCPs and pwMS need this type of information to challenge current treatment guidelines with evidence and more importantly, pwMS need this information to make potentially life-threatening decisions about their MS care. The number of patients on each individual DMTs is probably too small to make a definitive judgement, but sufficient to be reassuring.
So if any of my colleagues are reading this post please put your data out in the public domain ASAP and in a form that is accessible to all. There are several platforms for doing this including the weekly iWiMS webinars (see below) and the MSIFs Global Data Sharing Initiative. The latest data presented in the most recent iWiMS webinar is in line with the Italian data and remains very reassuring. It clearly supports the need to update treatment guidelines and develop an exit plan. At the moment I am still on version 4 of my DMT table.
So what are the wider consequences of asymmetric knowledge? To understand this you need to become an economics scholar. Asymmetric knowledge is an economic construct to explain the consequences of what happens where one party has more or better information than the other in a transaction. It creates an imbalance and can sometimes cause market failure, in this case, a potential moral hazard for pwMS and the wider MS community. Other, examples of this problem are adverse selection and monopolies of knowledge. I abhor the latter and it is particularly important that we try and fight it.
In addition to me falling out with several of my colleagues over this issue, many wars have been caused by asymmetric information. If you are interested in reading more about this topic I would recommend Joseph Stiglitz’s work; he won and shared the Nobel prize for economics in 2002 for “analyses of markets with asymmetric information”.
Sormani et al. An Italian programme for COVID-19 infection in multiple sclerosis. Lancet 29th April 2020
Excerpt:
On March 14, 2020, we sent the case report form to more than 200 Italian neurologists from about 90 multiple sclerosis centres across Italy. As of April 7, 2020, we have collected data on 232 patients from 38 centres, 57 of whom tested positive for COVID-19 and 175 of whom had suspected COVID-19 symptoms but did not have a positive test (appendix p 1). Mean follow-up was 12·6 days (SD 7·4). The severity of COVID-19 infection in 232 patients was classified as mild (no pneumonia or mild pneumonia) in 223 (96%), severe (shortness of breath, respiratory rates ≥30 breaths per min, blood oxygen saturation ≤93%, PaO₂:FiO₂ <300 mmHg/%, and an increase in lung infiltrates of >50% within 24–48 h) in four (2%), and critical (respiratory failure, septic shock, and multiple organ dysfunction or failure) in six (3%). Of the six critical patients, one recovered and five died; all had a positive swab (appendix p 2). 21 patients had undergone a 5-day course of methylprednisolone within 3 months before the onset of COVID-19.
CoI: multiple
Does mean you are restarting alemtuzumab infusions and HSCT?
Version 4 of the view is on line. Read for yourself
No, not yet. The problem with alemtuzumab is not the risk, which can be managed by shielding, but space and the resources to give the infusions. Alemtuzumab takes 6-8 hours to give and needs dedicated nursing time to monitor patients. However, we could give it subcutaneously; we have a protocol in place and have gone this route in a few patients. I would also argue that cladribine is a much better option given the science and risks that come with alemtuzumab. I wonder if NHS England would section switching all our alemtuzumab treated patients to oral cladribine during COVID-19?
HSCT is on hold at present and this is a problem because we were almost ready to start or STAR-MS trial to compare HSCT to alemtuzumab.
” STAR-MS trial to compare HSCT to alemtuzumab.”
Stop..it’s been done…published April 14, 2020….Autologous hematopoietic stem cell transplantation versus alemtuzumab in aggressive MS: a retrospective real-word study
https://n.neurology.org/content/94/15_Supplement/4096
“Conclusions: Intense immunosuppression followed by aHSCT is superior to alemtuzumab in reducing relapses and MRI activity in aggressive MS and promotes disability improvement.”
Thanks I will blog post on this
Interestingly, I was on a webinar a week ago that included clinicians and immunologists from Switzerland. They were planning to restart their HSCT programme in May.
My (Swiss) clinic told me earlier this week that they also didn’t suspend ocrelizumab which was a relief.
It might help that the clinic does not focus on infectious diseases so probably avoided becoming a hot zone.
My slant is that beta-interferons are probably the best deal for new MS patients; they were shown to be effective, in vitro, against the SARS virus. There is an ongoing clinical trial with SARS-COV2 patients, I believe. Be that as it may, patients with MS on OCR are 6, in the Sormani study. I would be interested to know if they are doing well. I am not a fan of S1P inhibitors, per se, given their side-effect profile and withdrawal phenomena/rebound.
The MSIF must follow real-time data metrics like the Johns Hopkins Corona virus website and data MUST be put out even as it is rolled out, without any delay, waiting for publication and peer review, etc. I know it makes for poor science but in these days of multi-media ‘action’ even journal publications come with words like, preliminary, not peer-reviewed, must be interpreted in the right context, etc. Moreover, it is an open secret that ‘drug studies’ are funded by the very private companies that folks abhor and those companies pay to publish in open access and other formats. We cannot have it both ways. Or when a journal editor published in his or her own journal !
Life, unfortunately, is now run by Twitter and Facebook and no one gives a rip about where the information is coming from. And meanwhile, the so-called experts themselves are all over the map. From outrageously erroneous projections of death and doom from Imperial College to wherever else, it is all mayhem, real or imagined.
“My slant is that beta-interferons are probably the best deal for new MS patients”…What do the people with MS say?.
Surely the risk is theirs, all recent studies show that newer agents are better than the interferons……The risk of MS verses the risk of COVID?
Editor publishing in their own Journal…Ha, Ha. My old bosses view was that we never did it, those days are gone, Hope about the issue of reviewers publishing in their own journal, do you every wonder why the same faces appear in the same journals:-)
I suspect we have said enough on editorial publishing practices and sponsored research.
Even the so-called federal research dollars do not go to the person or persons who write the most sensible protocols or try to develop new ideas, but to those who are in the ‘old boys’ club. The too is no secret.
Quote =My slant is that beta-interferons are probably the best deal for new MS patients
Not for treating MS they aren’t they are at best a piss poor treatment and at worst useless.
You wouldn’t prescribe a known ineffective treatment to a cancer patient and openly tell them it’s pretty crappy, their disease will spread and they will deteriorate in an uncontrolled manner but they haven’t ‘earned enough disability points yet’ to qualify for something that’s not shit. Yet doing so to PWMS is commonplace offering sub standard ineffective lazy treatments almost guaranteed to leave the PWMS’s life irrevocably and unnecessarily changed for the worse.
Acquired disability in MS patients is regarded as ‘inevitable’ and it is when patients are offered antiquated ‘horse and cart’ medications by lazy uniformed physicians rather than the 7 seater family estate.
Offering new MS patients rubbish meds ‘because it might be effective with C-19’ is insulting and ludicrous
My post was solely restricted to use of ‘MS medications during the COVID 19 pandemic’ and that too in newly diagnosed MS patients. The only class of drugs that have been shown to be effective against the cytopathic effects of SARS virus were the beta-interferons. If ANY OTHER drug has been shown to have something similar against any SARS virus that probably has great homology with the current SARS-CoV2, I will stand corrected.
The amino acid sequence homology between SARS-CoV and SARS-CoV-2 approximates to 75% for the spike proteins, and are 73.7% and 50.0% for RBDs (receptor binding domain) and RBMs, respectively. The prominent sequence differences between the crucial RBMs *receptor binding motif of SARS-CoV-2 and SARS-CoV raise a critical question of whether the binding affinity of SARS-CoV-2 spike protein to human ACE2 is comparable to that of SARS-CoV.
Given the above, beta-interferons are probably the best defense but I am not obviously suggesting that other drugs are less efficacious; all I am saying is that but that there is no proof that they blunt or can blunt SARS-COV2 and the best shot one has is perhaps beta-interferons.
The Imperial College projection, assuming a death rate of 0.5-1% and 60-70% of the population being infected was entirely reasonable. Indeed, it is only this that forced the backtrack from the laissez-faire herd immunity startegy to the social distancing policy that has thankfully kept the numbers of deaths lower so far.
But the imperial college estimates (Professor Neil Ferguson) of mortality were way blown out of proportion, if I am not mistaken and he himself apologized for his SNAFU. The only thing that CoV2 does is the R0 which was scary. The case fatality rate or ratio was 0.01 (Prof Jay Bhattacharya of Stanford U) and so it is blown way out of proportion. If people wear masks (at least moving forward), maintain social distancing (whatever that distance might be since that too is a moving target as an MIT study published in JAMA said that the actual distance ought to be 27 feet) and businesses are forced to work at 1/3 or 1/2 of their capacities but RETURN to WORK, some economic pain will ease. Lest, everyone is doomed. From joblessness or hunger or both.
The Imperial College predicted that over 500,000 people could die in the U.K., and over two million could die in the U.S., but Ferguson said he now expects the death toll in Britain to be under 20,000, according to NewScientist.
Thank you for this Prof G. It feels like a long lonely wait for information when you are self isolating.
I agree with this statement, I am currently
on Ocreluzimab and was due my infusion
in early April, my infusion was given in
the London dental institution next to the Royal London Hospital, I cannot praise the
nurses enough, there where only two patients at the appointment, and we where
completely separate from the main Hospital,
fantastic work, I can’t thank you enough XXX
” Or when a journal editor published in his or her own journal”
Boa
🙂
Wonder who that is aimed at….:-)
You know that there countless ‘editorials’, and opinion type articles !!
I am not going to be politically incorrect !!
We are jumping ahead here in terms of changing any guidance with quite weak data and study design on anything published on the impact of COVID on MS patients. Far too many confounding variables. We need to first understand the COVID virus itself – impact of varied strains, sub-populations at risk, immune response to the virus (the cytokine release hypothesis etc). The view on the virus itself seems to be changing weekly.
It’s two months today (19 May) since the Association of British Neurologists signed off their guidance for pwMS:
https://www.theabn.org/page/covid-19_patients
Info asymmetry notwithstanding, there is certainly more info available now (as you’ve demonstrated). Do you know of any plans for an update from the ABN? With lockdown progressively easing, no doubt plenty of folks on DMTs will be asking themselves what they should do for the best…
New guidelines are being finalised as I write this.
Brilliant – thanks.