Tuesday, 20 September 2016

NeuroSpeak & ResearchSpeak: effectiveness and safety of immunosuppressants

Long-term immunosuppression the new marketing battleground to differentiate DMTs. #NeuroSpeak #ResearchSpeak #MSBlog

"As promised a PDF of my slides from one of my ECTRIMS teaching courses on immunosuppressants. Immunosuppression, in particular long-term immunosuppression, was a hot topic at ECTRIMS for several reasons. The main driver, however, is that this will almost certainly become the next marketing battleground to differentiate DMTs from each other. One issue that came up was whether or not boosting your immune response to varicella-zoster virus with a vaccine would reduce your risk of getting shingles or zoster. Until we have definitive data we won't know. The study below of a new component VZV vaccine from GSK is very reassuring; it shows much better protection than the current live VZV vaccine. I would therefore urge all of the MS pharma companies to partner with GSK to do a large study to see if by boosting VZV immunity, in people who are VZV-seropositive, prior to starting an immunosuppressive reduces their risk of getting shingles or zoster. Please note that under current NHS vaccine guidelines we can't do this routinely. The only people we vaccinate with the current VZV vaccine (live attenuated vaccine) prior to starting an immunosuppressive therapy are those who are VZV-seronegative." 



Cunningham et al. Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older. N Engl J Med. 2016 Sep 15;375(11):1019-32. 

Background: A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). 

Methods: This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. 

Results: In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. 

Conclusions: In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229.).

7 comments:

  1. Having just endured a MAJOR case of shingles (L1-L4 involvement) I can be the poster child for any vaccine against this outbreak. I would take any and all vaccines to prevent recurrence, even if it means messing with my MS a bit! I'm sorry the NHS won't allow everyone to be vaccinated.

    ReplyDelete
  2. To:
    Professor Gavin Giovannoni:


    I tried to execute my post yesterday, but probably did an error. So I give it a try again.

    It is very hopeful that you bring up these immunosupressive drugs, Tysabri, Ocrelizumab, Lemtrada etc, as a possibility for some of us with PPMS.

    But I feel it could work for some not all. And we need also something else in the arsenal that is not immunosupressive. That said, you mentioned earlier, in a blog post 22 febr this year, that you were very optimistic about an experimental agent called Laquinimod.

    Source:

    http://multiple-sclerosis-research.blogspot.com/2016/02/researchspeak-reply-to-email-from.html

    I been waiting to hear something more about this drug. But after the above blog post, it has been totally quiet about it on the blog, at least to my best knowledge.

    I just wonder if you still have hope for this laquinimod in PPMS, or have your hope faded away as to your belief and hopes in this non-immunosupressive drug ?

    For some of us, as for me, without going into details about, I can not use heavy immunosupressive drugs for long duration, without taking very high risks. I have another disease than PPMS, that makes me very vulnerable for all these heavy immunosupressive agents.

    So then, I would like an honest answer, your honest personal opinion, about your beliefs in this non-immunosupressive drug laquinimod today ...?

    Sometimes silence speak, and I been watching out hear some more about this drug, given that you had very high hopes, aired especially in your blog post 22th febr this year.

    But things could change, new knowledge, new science, or some other bump in the road, that makes the rational for this drug less workable for patients with PPMS. If that is the case, then it which would explain the silence around this drug.

    I know it is good to think positively, but I prefer an honest opinion based on a solid rational, even if it is a personal rational, not shared by all, instead of only "hopes".

    Grateful to receive your honest answer or about this. Especially since all talks are now about these heave immunosupressive agents, and there are a few of us that can not take the risk to start to use those for different reasons. I.e. we need an effecient alternative.

    Please advice on this

    Regards
    Elisabeth

    p.s.
    I hope i will submit my post correctly this time
    d.s.

    ReplyDelete
    Replies
    1. Unfortunately there have been some safety issues with the higher dose of Laquinimod, forcing the company producing the drug to re evaluate their position and whilst they have continued their progressive trial with a lower dose, where the problem was not yet seen, given the small difference between doses makes one wonder what will happen. It is for the company to decide

      Delete
  3. As opposed to long term immunosuppressive therapy for highly active MS I would opt for short term induction therapies alem or even HSCT and proceed with revaccination. If a patient was low edss and remained jcv neg then natalizumab would be a good choice as an aggressive, highly effective therapy. JCV pos pts. Not on Natalizumab , maybe periodically check their ab titer for vzv to see if immunity is waning.

    ReplyDelete
  4. Dear MD,

    No offence ... but I would strongly like to have Professor Gavin input on this.

    WHY(?), well since he so strongly advocated for laquinimod in PPMS in his blog post 22th of february (see my previous blog post above), I think it would be fair if he, and not you dear MD, could answer and drop a couple of lines.

    In the same blog post professor Gavin also acknowledge the fact that the high dose was cancelled, but study is ongoing with 0.6 dose, which has been proven safe, at least what this professor Gavin states.

    So I would appreciate if you could hand over the previous blog post to him, and hopefully he will maybe answer :-)

    It is more of a follow up on his blog post 22 th february adn the silence since then.

    Warm regards
    Elisabeth

    ReplyDelete
    Replies
    1. I,m not good enough :-(
      DrK is the PI on the trial at Barts.
      Enjoy the wait :-)

      Delete
    2. Sorry, didn´t understand .. what means PI .. and who is DrK ?

      Kind regards

      Elisabeth

      Delete

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