Wednesday, 29 June 2011

Rituximab: a possible treatment for SPMS?

Rommer et al. Rituximab for secondary progressive multiple sclerosis: a case series. CNS Drugs. 2011 Jul 1;25(7):607-13.

Treatment options are very limited for MS'ers with SPMS. In this observational study the investigators present clinical and spinal fluid findings in 3 patients with SPMS who were treated with rituximab, a drug that target the B-cell or the cell that produces antibodies, for at least 15 months. During the observation period, no severe adverse effects occurred and the disability score stabilised in all subjects after a dramatic increase over the previous years. Conclusion: The investigators concluded that Rituximab seems to be effective in active SPMS. 

"What is wrong with this study? Firstly, it is very small; only 3 MS'ers. Secondly, it may be biased by the design, i.e. it is an open study. Thirdly, the EDSS is a poor outcome measure and too insensitive for change over such a short period of time. Do you think this paper should have been published?"

"What is right with this study? The investigators should be complemented for trying Rituximab in SPMS. In the past this is how therapies evolved; you started with an idea or scientific rationale and you then test the drug in an individual with the disease. If it appeared to work in the individual you then test it in a few more cases; this is called a case series. If the results then look promising you do a trial. Unfortunately, the regulatory, ethical and financial constraints in the NHS means that this classical route of investigator-led drug development is now virtually non-existent. It is becoming increasingly difficult to get PCTs or Commissioners to pay for off-license use of drugs like Rituximab. The usual response to an individual funding request to a PCT is "NO"; particularly if it is the off-license use of an expensive drug. Ultimately, this will hamper medical discovery and staff in the NHS will drop down the league tables of innovation. It also means that drug discovery will become almost the exclusive reserve of the Pharma Industry; this is something we should try and avoid as the needs of Pharma are often at odds with the unmet needs of MS'ers (please see previous posts on oral cladribine). Any thoughts on this?"



9 comments:

  1. Wow, this is the best site I’ve ever read. Thank you for sharing this.clinical research in india

    ReplyDelete
  2. My thoughts are that this is pretty encouraging in one way (i.e. the results of the study) but depressing in another (i.e. 'the classical route of investigator-led drug development is now virtually non-existent'). If people with SPMS knew there was a drug that could (possibly) help to stabilise them and prevent further deterioration I believe they would be clamouring for further research to take place. How can we make this happen?

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  3. Prof G,

    My thoughts:

    Rommer et al should be congratulated for this very small study. They wanted to test it on humans, they got on with it, it looks like the 3 patients benefitted.

    I'm not sure how much Rituximab costs ?£10,000, and there is the cost of MRIs, analysis etc. But not a huge amount. Given that Gilenia will cost c.£20,000 a year it doesn't look a bad deal.

    Too much paper work involved in running big trials in the UK. Ethics Committees? What do they do? I find it unethical that there might be treatments which could help people with progressive MS, but they aren't given the choice. Safety? We are obsessed with safety. When we are talking about a disease which eats your brain away and gives you an early death - why worry about safety? We've built a monster of a bureaucracy in the UK that prevents lots of trials getting underway and, therefore, does not serve the interests of the patient and their families.

    Bring back this case series approach. The Phase I-III studies play into the hands of the big pharms companies.

    If I was you Prof G, I'd run a little trial of one of the neuro-protective agents (which ahve been identified) on 10 patients and use your approach for testing efficacy (spinal fluid tests). This wouldn't cost a bomb - happy to contribute to it. I think you respect this approach - in the business world it's the equivalent of SME (innovative / entrepreneurial). A couple of these small scale studies would give you back your mojo.

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  4. Opexa therapeutics- OPXA announced its initiation of it clinical trial yesterday for SPMS.
    Thoughts on this promising trial?

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  5. They have a product named T celna and it was previously Tovaxin which is based on the concept of T cell vaccination and inhibition of T cell function. T cell immunosuppression has not yet stopped SPMS so far and so on first glance it is hard to see how this is this being different, unless the mechanisms of disease control offer something new.

    However on their website it says
    "subject to securing the necessary resources", so the announcement is a fund raising excerise.

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  6. Dear Anon 11.39 why ask this question here rather than on unrelated blogger comments that are their today rather than post in PAST posts mentioning SPMS
    and again in another?

    It makes me suspicious that this an Opexa marketing plug?

    Do you want to know what T cell vaccination is?

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  7. There was clinical trial reported with Tovaxin
    http://www.ncbi.nlm.nih.gov/pubmed/22065170

    I would like to see data showing that it could do something mechanistically useful to SPMS that is not the same old same old T cell inhibition

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  8. No response from Anon 11.39 yet, so I guess comment is just acompany plug, which should therefore be ignored

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  9. I TO FEEL THAT BIG PHRMA HAS TO DO WITH THIS MATTER.WHY CANT THEY JUST LET IT GO AND LET THOSE WITH SPMS GET SOME RELIEF.

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