Buyers Club..Don’t Buy Duds.


ProfG has created an off-label list of DMT. Many of them are based on the generic version of current MS drug, or a generic pro-drug of an active MS drug.

You perhaps would thought that Charities would want options for all people with MS, including those in resource-poor environments to have options. These studies could have been done by now, but my experience with generic cladribine told me otherwise. I don’t buy the idea that generics are second best and it is now only a matter of time before chemical generics arrive. Will we get change then? I have my predictions. However I get chastised for making these.

If you go to the effort of a buyers club, it is important that you don’t put duds into the mix.

ProfG asked about methotrexate?

Methotrexate was made in 1947 and initially came into medical use to treat cancer, as it was less toxic than the then-current treatments. Methotrexate is available as a generic medication. The wholesale cost as of 2014 in the developing world is between US$0.06 and US$0.36 per day for the form taken by mouth. It is currently used in rheumatoid arthritis alot.

I thought I would have a look at the effect on memory B cells. There is not much in multiple sclerosis, but there are a few studies in rheumatoid arthrits and they say the same thing.

The prediction is perhaps clear to me?

So what happens in MS?

Ashtari F, Savoj MR. Effects of low dose methotrexate on relapsing-remitting multiple sclerosis in comparison to Interferon β-1α: A randomized controlled trial. J Res Med Sci. 2011;16(4):457-6

Eighty patients with definite RRMS aged 15 to 55 years were randomly allocated to receive a 12-month treatment course of either oral Methotrexate (7.5 mg/week) or intramuscular Interferon β-1α (30 μg/week). Response to treatment was assessed at 12 months after start of therapy. The results of the study demonstrated significant reduction in relapse rate in both groups (p < 0.01). In 40 patients treated by Methotrexate, the mean value (SD) of relapse rate decreased from 1.75 (0.74) to 0.97 (0.83) (p < 0.01). Correspondingly, the mean value (SD) of relapse rate in patients treated by Interferon β-1α decreased from 1.52 (0.59) to 0.57 (0.78) (p < 0.01).

So not as good as beta interferon in this study:-(

Now I could pull out a paper showimg.methorexate slowed the progression of deterioration of hand function, suggesting promise.

That is not the point.i am trying to make. My point we there a agents that are more potent than others, and this needs to be thought about as putting people on low efficacy options may not be the best plan

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  • MD you mustn’t forget that relapses and focal MRI activity are not the disease, i.e. MS, therefore, you can’t say that methotrexate is a dud. The other problem is that the dose has not been optimised. In real-life when we use methotrexate to treat RA or sarcoid we titrate the dose based on treatment response. You could be on anything from 7.5mg up to 25mg per week. I think we need to do a trial of methotrexate using an adaptive dosing strategy. What do you think?

    • Totally agree and am aware of the hand data from the trial in MS, so it surely must be doing something.

      However, the point I was trying to make (perhaps not too well) is that based on what we know, there is a hierachy of efficacy amongst current DMT. Likewise, there will be a hierarchy of responsiveness in relation to the off-label options.

      Azothioprine is as cheap as chips, but there was a head to head study against beta interferon and they came out about the same. Therefore if we put our eggs in the azothioprine basket your end result may be as good, or as bad as beta interferon. Based on what we know rituximab and cladribine for example would be clearly more efficacious at least with respect to relaspe. Therefore there is an opportunity to maximize potential benefit if you go down the route of a club by selecting . Methorexate is used as a add-on in arthritis and this may also offer benefit as an add on, it may be offering neuroprotection potential. However if relapse is the otuome and this is the dose you plump for

  • That’s because they used a homeopathic dose of methotrexate. Do the trial again with double the dose and the results would be different.

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