Q&A June 2020


Want to Ask a Question this is the place for You

Springwatch….There was some strange holes in the grass….so we got a night camera guess what we found?

About the author



  • Hello! So glad I found this blog, it’s been a huge help over recent weeks and (as a cell biologist) I loved last weeks new DMT/COVID paper- fascinating stuff and great that immunomodulatory therapy mechanisms are being given consideration in terms of cellular subtypes. Just a quick question- given the below from a previous post, does this imply that patients on natalizumab therefore most vulnerable (in terms of neurotrophic infection) immediately following infusion?

    “The theory behind EID is that some cells are less sensitive to the effects of natalizumab and that if you delay the next natalizumab infusion by 1 or 2 weeks the saturation of their surface receptors drops below a threshold and allows these cells to traffic into the central nervous system.”

  • nice find
    question re treatments
    With Cladrabine being relatively easy to use and dose, do you think it will eliminate other oral DMT’s that claim similar efficacy. compliance is almost set at 99.9% (there’s always someone) and its been shown / claimed that other oral DMT’s are luck to be at 70%. If people are not compliant then its not working. Does this sway peoples prescribing to it due to its ease compared to a similar oral DMT??

    The major issue with feedback from pts is they worry about when to re-dose being a bit vague do you just go ahead and do it at 3 years or wait till there’s issues

  • Hello! What is your current strategy at Barts for people on natalizumab who are concerned about PML but are doing well? Do you move them to EID? Do you switch them to another treatment and if yes, which one?

  • Posted this last month, would like to hear your opinion, and also there was a question about MRI contrast -which is also relevant as it’s required to highlight inflammation to access these treatments…
    “Is there any point in considering treatment(for PPMS) with ocrelizumab or (off-label) cladribine, considering without current inflammation, even although the current eligibility states that there needs to be current (proven) inflammation?”
    I am desperate for a treatment as progressing rapidly but there want proof of current inflammation on last MRI or LP.

  • Do you live in the countryside? How amazing to see. We just want a hedgehog to visit our back garden.

  • Hello everyone,

    I am not asking for a personal opinion. But I would like to have your thoughts on this situation on general. And maybe some other readers of thé blog had face a similar situation ?

    I have been on DMF for 1 year and a half (ie since my diagnostic) and have been NEDA3 so far (and EDSS at 0) but I want to switch for ocrelizumab for the reasons we lnow on this blog.

    My medical team refuse me that. They argue that ‘I am perfectly responsive to DMF so changing for another DMT is not safe’.

    What do you think ? What can I answer to them ? Do you have some advices for me in order to convince them ? I think someone on this blog (@Dominic ?) had to fight also to switch from DMF to OCR.

    @Prof G : By the way the Professor in charge of the medical team (who is a ms specialist) know you well I heard.


    • Ms its a battle

      In a battle you are never safe

      Only the Doctors are

      Its not their brain that are burning

      Ps: Time is brain

    • “fight also to switch from DMF to OCR. ”

      Would not switch to Ocrevus as Alemtuzumab and hsct seem superior to it.
      But most have to really..really fight to get those.

  • With the second peak being( ancedotally obviously) by funeral directors and some NHS staff beginning in June and deaths being very high in July, what are the odds on Neuros giving the go ahead for Ocrevus treatment to begin for the first ever round in July I wonder?

    Also, is it possible to get high dose vitamin D on prescription from the neuro (pre-paid certificate)?

  • Well trained? I guess it is to spread the pee it was rolling around in. I dont know any ideas?

        • We are all card-carrying socialists here; we believe is socialist medicine. Unfortunately, the Big Pharma system we have created doesn’t allow for successful alternatives; unless there is massive and I mean massive risk-taking and investment from the governments of the rich-world.

  • Been on DMF for 5 years, lymphopenic ever since (between 0.5 and 0.7). I’ve had a serious infection last year, that lasted for over a year. It’s not a stretch to think that persistent lymphopenia (and indirectly DMF) is a probable factor here?

    • Overall Safety and Efficacy Through 10 Years of Treatment with Delayed-Release Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis


      Of 618 patients with follow-up for ≥10 years, 192 were continuously treated BID (192/501, 38% of the overall continuously treated BID population). Mean (SD) age 41.6 (8.7) years; 68% female. Fifty-one percent (98/192) of patients remained relapse-free; 73% (141/192) had ≤1 relapse; ARR over Year 0–10: 0.107 (rate ratio vs.10-year placebo/DMF 0.603 [p=0.018]). Median time to first relapse was 518 weeks. At baseline, mean (SD) expanded disability status scale (EDSS) score was 2.24 (1.18). Patients with EDSS ≤3.5: 164/184 (89%) Year 2, 148/184 (80%) Year 8, 146/184 (79%) Year 10. Over 10 years, 64% (122/191) of patients had no CDP. Overall, 77 (40%) patients experienced SAEs; most were MS relapse (18%, 34/192) or infections (6%; 12/192). Over 10 years, there was no increased incidence of serious infection. Patients remained stable on SF-36 and EQ-5D from baseline to Year 10.


  • Its zealots time : )


    Conclusions: While it is imperfect to indirectly compare treatments from different studies, EDSS outcome patterns between aHSCT and alemtuzumab differed remarkably. aHSCT, in contrast to alemtuzumab, was associated with the largest magnitude of fall in EDSS that was sustained in the long-term to five years. A direct comparison of aHSCT with alemtuzumab in a RCT seems warranted to confirm these observations of long-term benefit with aHSCT.


    Ebmt 2020

  • Vacines and Hsct
    Conclusions: Re-vaccination in patients who underwent an autologous HSCT for a severe autoimmune disease is a common practice in many centers and is also recommended in the EBMT guidelines. However, some concerns about this practice were raised for the putative role of vaccinations as an autoimmunity trigger. In the literature there is no study on the loss of protective antibody titer in either natural or vaccination-driven immunity with regards to patients transplanted for autoimmune diseases. In our series a high variability in antibodies titers at baseline was shown. The larger subset analysed confirms that most patients showing a protective titre against the tested agents, show a trend to maintaining it. A possible approach might be to revaccinate the patients with unprotective titre at 2 years after HSCT, taking into account the individual risk of being exposed to the infection; a larger series of data is necessary to provide conclusive evidences on this topic.

    Ebmt 2020

  • Its all about the $$$$$$$$


    Results: Mean direct costs were $42,295 (range $33, 887 to $57,704), mean indirect costs were $42,888 (range $33,653 to $62,555), and mean total costs were $85,184 (range ($70,635 to $120,260). Mean revenue collected was $95,268 (range $16,544 to $173,204) and mean net income (profit) per patient was $10,084.


    Ebmt 2020

      • Burt charged like $200,000 and his staff would get insurance compaies to pay by telling them patients would save money by going off dmt. Heard of people taking out mortages…Know someone
        who was told by Burt he would treat her if she had just one more mri lesion.. Her husband said..that makes no sense..let’s just go to Mexico. Mexico has treated 1,000 patients at $50,000 for 50 million revenue since 2015…and only 2 patient deaths both being edss 8+.
        Meanwhile U.S. has 1 million ms patients and not one place that does hsct. But neuros still use betaseon and copaxone here.

  • First, I would like to thank all the authors for their amazing work on this blog! This blog has been a lifesaver in terms of providing thoughtful insights on current MS research, something I haven’t found anywhere else.

    My question is based on the fact that aHSCT seems to work best on younger, recently diagnosed patients with a low EDSS score AND fewer previous DMT failures. The first 3 criteria make sense to me (age, disease duration, disability level), but I’m curious on why previous DMT use can predict an increased likelihood of aHSCT failure? The obvious answer is that those who failed several DMTs have a more aggressive form of MS that is harder to treat, but is there any mechanistic reason on how certain DMTs could lower the efficacy of aHSCT or other IRTs? Could some drugs possibly cause changes to lymphocytes that make IRTs less effective later during the disease course?

    • “but is there any mechanistic reason on how certain DMTs could lower the efficacy of aHSCT or other IRTs”

      Moot point…Why even go on DMT…? Just go straight for IRT .

      • Yes, that was where I was heading with the question. All these HSCT trials require DMT failures, which could actually be worsening IRT outcomes through drug induce immune senescence. This argues that HSCT and Lemtrada should actually be first-line treatments, not only because they’re more effective early on in the disease course, but because other drugs could make them ineffective. I have not seen this argument in the literature though

        • AHSCT has been designated as a clinical
          option in the EBMT guidelines for the treatment
          of patients with aggressive MS that is unresponsive to
          conventional and approved therapies63. However, a
          critical point for patients and clinicians to understand
          is that AHSCT is not a neuroregenerative treatment
          or a treatment that should be used as a last resort after
          failure of all available treatments. Rather, the optimaltiming is immediately after failure of licensed treatment,
          when the aggressive clinical course of the disease
          is clear but the patient remains minimally compromised.
          The current evidence enables us to refine the profile of
          the ideal candidate for AHSCT on the basis of several
          important factors: relapses and the phase of the disease,
          MRI activity, age and disease duration, neurological
          disability, comorbidities, cognitive impairment and
          response to prior treatments
          (BOX 2

          Previous response to MS therapies.

          For patients with average active MS (which is distinct
          from aggressive), the current prevailing opinion is
          to initiate treatment with a first-line therapy, followed
          by escalation to natalizumab, fingolimod or alemtuzumab
          in those who fail to respond89. In our opinion,
          escalation through two lines of therapy before considering
          AHSCT is acceptable but not required: patients who
          experience persistence of their disease or breakthrough
          of substantial clinical and MRI inflammatory activity
          during induction treatment with a high-efficacy monoclonal
          antibody (as defined above) administered as a
          first-line therapy could be considered as candidates for
          AHSCT, as well as for alternative approved high-efficacy
          treatment options. However, prior treatment with more
          than two immunotherapies is associated with poorer
          progression-free survival after AHSCT61, highlightingthe limited window of opportunity for effective MS treatment,
          and the fact that treatment escalation over several
          years precludes the chances of success with any treatment
          that is given too late. With >10 currently approved drugs
          for MS, the risk of missing this therapeutic window
          is of
          particular concern.

          Autologous Haematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis


    • We will have to wait for the results but using an antibody to treat something inside the brain is not the most sensible approach

    • No, not new we showed info of statins on endothelia twenty years ago. If this is about progression why as they looking at blood vessels with relapsing MS Sera. I’ll have a proper look and update my response

  • Recently somebody I know posted an extract from an article in a Whatsapp group. The article is written by JK Rowling and includes the following statement ‘I also fund research into MS, a disease that behaves very differently in men and women…’

    How does the disease behave differently in men and women. The only difference I am aware of is that it is more common in women than men.

  • As I possibly am asking people who has glandular fever as a child.. Did you get any special educational allowences, help or support at school for the time you had off school, sick at home?

    The talk of school children having their education damaged, by time off school due to Covid-19 has made me think..

    I didn’t get any allowences/ help/ support and I was off for several months and then had relentless fatigue after that.

    • The glandular fever did impact on my social mobility (my education). And that was before my MS reared it’s ugly head, damaging my social mobility even more.

  • T time

    For Doc Mouse

    Aparently you dont need the antibodies in Sars cov 2

    And the test to diagnosed covid-19 should be made to t cell instead


    Background. In the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results. Methods. Here we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls. Results. All index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection. Conclusion. Exposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus

    Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion


  • What is the reaction of BartsMS to the decision by NICE to reject Siponimod as a treatment for SPMS? Seems like another kick in the pants. 2020 is shaping up to be a really bad year

  • Covid-19

    10 000 Milions

    The milestone is a rebuff to health experts and global leaders — including U.S. President Donald Trump — who had hoped early in the pandemic that the virus would fade away with the summer heat. Instead, infections are multiplying faster than ever.

    How said that summer who ease virus trnasmition?

    Not me 🙂


  • T time
    part 2


    Immunity to COVID-19 is probably higher than tests have shown

    One interesting observation was that it wasn’t just individuals with verified COVID-19 who showed T-cell immunity but also many of their exposed asymptomatic family members,” says Soo Aleman. “Moreover, roughly 30 percent of the blood donors who’d given blood in May 2020 had COVID-19-specific T cells, a figure that’s much higher than previous antibody tests have shown.”

    Patients with severe COVID-19 often developed a strong T-cell response and an antibody response; in those with milder symptoms it was not always possible to detect an antibody response, but despite this many still showed a marked T-cell response.


    Second study basically showing the same thing


    • Not second I think there are others but much appreciated it, but it is evident that some of those T cell responses may be cross-reactive to previous infection with cold causing cornonaviruses and in those cases often the T cells do not recognise the nucleocapsid, which is the basis for many antibody tests.

  • Its B aker time 🙂

    B cells and their function in the immune system

    Maybe you dont need anti cd 20 antibody to get rid of B lymphocytes 🙂

    B cells die more easily without Pdap1

    “A particularly surprising finding to come out of our in vivo experiments, however, was that mouse B cells that are unable to produce Pdap1 die far more easily than is normally the case,” adds Di Virgilio. Her team discovered that the protein protects B lymphocytes from stress-induced cell death. “Mature B cells experience cellular stressors particularly when they begin to grow and proliferate rapidly after contact with the pathogen,” explains the researcher.

    It seems that in unmodified animals, Pdap1 helps B cells to cope with this stress. Without the protein, however, a program is started that ultimately leads to cell death. “So Pdap1 not only helps the B lymphocytes to consistently produce the effective antibodies,” says Di Virgilio. “It can also be seen as their protector.”




Recent Posts

Recent Comments