Do MS drugs stop the development of SPMS?

D
You asked what ProfG thinks of this paper.

To answer that question

I don’t think much

Paper

Coret F, Pérez-Miralles FC, Gascón F, Alcalá C, Navarré A, Bernad A, Boscá I, Escutia M, Gil-Perotin S, Casanova B. Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies.Mult Scler J Exp Transl Clin. 2018 Jun 26;4(2):2055217318783347. 


BACKGROUND: Disease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis.
OBJECTIVE:To explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing-remitting multiple sclerosis patients.
METHODS: Our study included 204 patients treated for relapsing-remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan-Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion.
RESULTS: Relapsing-remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1-18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0.
CONCLUSIONS: The favourable influence of disease-modifying therapies on long-term disability in relapsing-remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

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I think the title is misleading as it states that current DMT do not stop progressive MS from occurring. However, the census period was 1995-2002 and so simply read it as ‘CRAB drugs do not halt progression’. However you know my views and I would replace the B with a P. The CRAB drugs were and are simply not potent enough so really get disease under control for most pwMS. 

Therefore, I don’t want to spend time discussing conclusions based these agents. ProfG will say look at the survival time the CRAB drugs improved it. So they aren’t inert.

Not sure if these investigators understand that SPMS is an artificial (Pharma invented) construct and that progressive MS is there from the beginning; it doesn’t suddenly come on. When is the community going to accept that ?


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MouseDoctor

11 comments

  • OK so SPMS is a pharma construct so lets call it advanced MS. What progress have we seen to date to help people who suffer from advanced MS now and yet to reach that stage. Waiting to hear on MS-SMART otherwise radio silence in the UK. MS-CHARIOT not yet given the green light. Come on, give us something to help us get out of bed in the morning, something to slow down the progression to social isolation and total disability

  • "Waiting to hear on MS-SMART otherwise radio silence in the UK."
    All these trials are being done by U.S. Pharma and Tisch MS
    But at least this blog comes out of the UK.
    ________
    Dr. Sadiq Tisch MS Center

    “Repair and regeneration is possible. We have a patient who no longer needs her cane, one who has transitioned from a motorized scooter to taking steps with a walker and another who has discontinued their bladder medication as those symptoms have dramatically improved. This is the first treatment that improves established disability in patients with progressive MS and shows us there is hope that a future treatment is possible,” stated Dr. Saud A. Sadiq.
    https://www.ebiomedicine.com/cms/attachment/2119347504/2092552776/gr2.jpg
    https://www.ebiomedicine.com/article/S2352-3964(18)30051-3/fulltext
    ____
    Atara Bio
    https://imgur.com/niGAJWi
    60 y/o SPMS EDSS 6.5—6.0
    60 y/o PPMS EDSS 5.0—3.5
    ________
    Principia Bio: Distinct from other BTK inhibitors PRN2246 readily permeates the blood-brain barrier(BBB)

    https://www.principiabio.com/pipeline/btk-prn2246/

    • MS_SMART, so to be published soon, oxcarbazapine is being analysed and more news of progressive studies in UK will surface.

      The Tisch needs to do a proper blinded study, otherwise it is a drip feed of self-serving positive data.

    • If patients disability is reversing. How is a double blinded placebo trial going to show any thing more other than costing billions thus making tisch sell their treatment to pharma who can then justify charge mark up of price by 500%. Even FDA has relaxed rules on gold standard.

  • Is there any studies done thus far MD on any of the newer more potent DMDs (B cell inhibitors) that show a decrease in conversion from RRMS to SPMS?

    I remember a while back you had a publication that showed all MS drugs, even CRAB drugs, worked through inhibiting B-cells. Wouldn't one expect the CRAB drugs to at least have some effect, even minimal, on delaying transition of RRMS to SPMS?

    • The problem is lumping everything together you say the CRAB drugs have small effect or no effect but we do not stratify those that are responding well to say B cell depletion and those that do not. So you are adding noise to the system.

      There is data from MSbase presented this week that report slowing of conversion

  • "SPMS is an artificial (Pharma invented) construct"

    Agreed. Meaning that part of patients that don't respond to drugs and should not be part of trials. The conclusion remains the same: CRABs are useless, despite the early hype and huge sales since their launch. It is a matter of time to see the same conclusion arise for modern age drugs. It would be more difficult to swallow, however, but luckily we have that EBV-lifeboat by our side…

  • "In conclusion, we consider it likely that long-term treatment with DMTs might reduce the number of patients who will develop SPMS. However, in patients who do convert to SPMS, time to conversion, age of transition and subsequent cumulative disability are not influenced by current therapies."

    Obrigado

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