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Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, ... double-blind, placebo-controlled study, 2021, Krishnan et

Discussion in ''Conditions related to ME/CFS' news and research' started by Hutan, Oct 16, 2021.

  1. Hutan

    Hutan Moderator Staff Member

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    Australia
    Abstract
    Background
    Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain, leaving patients incapacitated for months to years. With no available vaccine or specific therapeutic for any alphaviral disease, and a growing economic and public health burden, there is a serious need for the development of specific therapies.

    Methods
    This study evaluated the safety and efficacy of pentosan polysulfate sodium (PPS) in subjects with RRV-induced arthralgia in a double-blind, placebo-controlled trial. Twenty subjects were randomized 2:1 to subcutaneous PPS (2 mg/kg) or placebo (sodium chloride 0.9%) twice weekly for 6 weeks. Safety evaluation included physical examination, concomitant medications, and laboratory findings. Efficacy assessments included change from baseline in joint function (hand grip strength and RAPID3) and quality of life (SF-36) at Days 15, 29, 39 and 81 after treatment initiation. Inflammatory and cartilage degradation biomarkers were exploratory endpoints.

    Results
    PPS was well tolerated, with a similar proportion of subjects reporting at least one treatment-emergent adverse event (TEAE) in the treatment and placebo groups. Injection site reactions were the most common TEAE and occurred more frequently in the PPS group. Dominant hand grip strength and SF-36 scores improved with PPS at all time points assessed, with hand grip strength improvement of 6.99 kg (p = 0.0189) higher than placebo at Day 15. PPS showed significant improvements versus placebo in adjusted mean relative change from baseline for RAPID3 Pain (p = 0.0197) and Total (p = 0.0101) scores at Day 15. At the conclusion of the study overall joint symptoms, assessed by RAPID3, showed near remission in 61.5% of PPS subjects versus 14.3% of placebo subjects. Additionally, PPS treatment improved COMP, CTX-II, CCL1, CXCL12, CXCL16 and CCL17 biomarker levels versus placebo.

    Conclusions
    Overall, the improvements in strength and joint symptoms warrant further evaluation of PPS as a specific treatment for RRV-induced and other forms of arthritis.
     
    Peter Trewhitt likes this.
  2. Hutan

    Hutan Moderator Staff Member

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    I thought this paper was interesting given the discussions we have had about whether there might be a spectrum of post-viral conditions ranging across ME/CFS, fibromyalgia and overt arthritis resulting from chikungunya.


    It's also interesting to see Australian virologist Lara Herrero as an author, given her comments in a recent article.
     
    Last edited: Oct 17, 2021
  3. Hutan

    Hutan Moderator Staff Member

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    Interesting re the placebo effect on subjective endpoints:
     
    Peter Trewhitt, shak8 and Trish like this.
  4. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    That sounds like a new way of scratching around for an excuse for not getting any results doesn't it?

    I am not impressed with the 'biomarkers' they chose to report - biomarkers of what? Why not give results for something we know a bit more about like CRP or ESR?

    I suspect pentosan polysulphate is quite irritant so this may not be realistically blinded.
     
    FMMM1 and Hutan like this.
  5. Hutan

    Hutan Moderator Staff Member

    Messages:
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    Location:
    Australia
    Yes, the results for the treatment don't look very exciting. And the authors suggest that maybe they need to dose at a higher rate, which could also be a way of scratching around for an excuse for not getting any results in this experiment. Perhaps they will find something with that treatment eventually, although probably not.

    But I thought it was an interesting paper due to the apparent acceptance that alpha viruses including Ross River Virus can cause joint inflammation and pain. (Whereas, the discussions here have been a lot less certain about that.). And we know RRV causes a post viral fatigue syndrome that can meet ME/CFS criteria.

    I heard a young woman who has idiopathic juvenile arthritis, which she got after a virus, on the radio the other day. As well as a lot of pain, she talked about 'paying' for exertion on the days following, and life-limiting fatigue, in a way that sounded a lot like PEM. That together with the joint pain that my son had, and that I currently have makes me think that maybe there are some commonalities in ME/CFS and inflammatory joint conditions.
     
    Last edited: Oct 17, 2021
    FMMM1, Sean and Trish like this.
  6. Mithriel

    Mithriel Senior Member (Voting Rights)

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    One of the symptoms of ME before CFS was joint pain which could affect different joints at different times.
     
    Hutan likes this.

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