There are so many killjoys out there who think progressive MS is an intractable problem and that we have no treatments that work. Incorrect! I would like to remind these killjoys of the cyclosporine and methotrexate studies from over 25 years ago in people with chronic progressive MS (SP & PPMS). Both these studies were positive and had an impact on disability progression. Cyclosporine was dropped because of renal toxicity and hypertension and methotrexate was dropped because most people think that protecting the upper limbs in people with progressive MS is not worth doing.
The above is water under the bridge, right now we should be celebrating the recent results of ocrelizumab in PPMS and siponimod in SPMS, results. The killjoys say these results are not good enough. What do you want? Please remember a 25% difference in progression rates at
at 2-3 years of follow-up may be 50% at 5 years and 75% at 10 years. I agree that if you have progressive MS these results are not what you want; you want to get back to normal. However, these drugs are not designed to restore function; for that to occur we need new therapies to add-on to anti-inflammatory therapies. Please be positive and celebrate the recent successes in progressive MS. The tragedy is we had similar successes over 25 years ago and we didn’t build on them. This time we need to seize the day; carpe diem!The Multiple Sclerosis Study Group. Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. Ann Neurol. 1990 Jun;27(6):591-605.
Goodkin et al. Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann Neurol. 1995 Jan;37(1):30-40.
Methods: A randomized, double-blinded, placebo-controlled, clinical trial of low-dose, weekly, oral methotrexate was performed in 60 patients with clinically definite chronic progressive multiple sclerosis (MS) attending a referral-based outpatient MS clinic. Study patients were 21 to 60 years old with a disease duration of longer than 1 year. Patients’ Expanded Disability Status Scale scores were 3.0 to 6.5 (ambulatory with moderate disability). Patients were first stratified by Expanded Disability Status Scale scores, 3.0 to 5.5 and 6.0 to 6.5, and then were randomized to receive methotrexate or placebo treatment. Treatment consisted of weekly, oral, low-dose (7.5 mg) methotrexate or identical placebo for 2 years, followed by observation for as long as 1 year. A composite outcome measurement instrument was used and consisted of (1) Expanded Disability Status Scale, (2) ambulation index, (3) Box and Block Test, and (4) 9-Hole Peg Test.
You are a hero not just in the neurological community but in the medical world generally for this kind of public engagement. It matters.As someone with PPMS, I'm listening to this message. My concern is not unrealistic expectations regarding efficacy. As a single mother in her 40s, I am concerned about malignancies with Ocrevus. How to consider the balance of risk and benefit when a patient is willing to end up in a wheelchair — isn't the mean for PPMS 50-50% in 20 years — than significantly raise my risk for cancer and leave my child without a caregiver because of an intervention I chose.
Prof G is med-mad. He believes that pill-popping remedies all, and side effects are worth it all.
Yep…because that view is supported by data.
I thought the mean time to the wheelchair is 20 years from onset for RRMS and not PPMS?Could someone verify this?
I was referring to some natural history studies. Here is one: https://www.researchgate.net/publication/262341244 Mt. Sinai in NY recently published a study of their PPMS patients showing even slower progression rates. This is interesting for all of us who will be thinking about risks and benefits and new treatments are approved.
"Methotrexate was well tolerated at the low doses used in the research. Longer-term use may be associated with serious side effects, including lung and liver problems, and the suppression of bone marrow. As a result, methotrexate is not a first line treatment for multiple sclerosis."https://www.mstrust.org.uk/a-z/methotrexate-maxtrex#sideeffects"If you had progressive MS would you consider methotrexate?"I have PPMS and personally, no, I would not. It seems it would maybe be a case of choose your poison – PPMS alone, or PPMS with methotrexate. Not a good choice – the devil or the deep blue sea sort of thing.I'm not celebrating Ocrelizumab, at least not at the moment. Safety issues concern me.
I was on the ASCEND trial. At the time my problems were mobility and I did not notice any flatlining to my progression. Now I am on MS-SMART trial since Jan 2017. I have noticed tasks with my hands such as writing are becoming a lot more difficult and also my mobility declining. Without FES I would definitely be in a wheelchair. Watching my decline does not make me a happy bunnyUtopia to me would be treatment that will flatline progression
Sorry to hear that you feel you are deteriorating but we have to rememebrMS-SMART is a placebo controlled trial and so 1 in 4 people get the placebo and as ProfG has suggested drugs may not flatline but change the slope of worsening.
What kind of FES are you using Patrick? It's new to me and since my spastic leg is causing problems I'd like a tip how to improve it.
I am using a two channel FES. It is a bit of aa faff to setup correctly and it takes a bit of practice and experience. I sugggest you go back to the clinic that issued it to you and talk to them.
The trouble with treatments for progression is that Prof G and co think a slowing down, possible flatlining is great. I want something more than just watching myself deteriorate at a slightly slower pace. Are you really that pleased with the efficacy of treatments in the pipeline for progressive MS? If someone is diagnosed with PPMS tomorrow there is NO treatment that can be offered. Yet Prof G thinks everything is hunky dory and we should stop moaning. How brave people are who don't have have to face watching themselves deteriorate.
HSCT has stopped progression in PPMS. They are now offering it in London if you have active lesions. Other places will offer it without active lesions.
This claim needs a privio, the data is that progressive MS is less likely to respond to HSCT, so not all people will get total benefit. Those with active lesions are more likely to benefit.
I did four doses of methotrexate – – one year. I could not tell that it affected the course of my disease at all and I suffered with the side effects (nausea) plus the time and unpleasant experience of being infused. The costs are real and the benefits are very blurry.