It is clear how the MS community feels about ocrelizumab for PPMS #ClinicSpeak #ThinkHand
I have previously discussed the concerns many neurologists have about the risk-benefit ratio of ocrelizumab in PPMS. Ocrelizumab is a much more potent B-cell depleter than Rituximab, i.e. ~10x as potent. A 600-mg dose of ocrelizumab is ~6x more potent than 1,000-mg dose of rituximab. This may explain the efficacy difference between the two monoclonals; particularly if ocrelizumab is targeting the hard to get to meningeal and intrathecal B cells.
After some of the comments on this blog we ran a survey to poll what pwMS thought about the ocrelizumab results. It is pretty clear that for pwMS ocrelizumab represents a real advance and the beginning of something very important for them. We now have something to build on. Let’s hope we see a large number of new trials exploring other DMTs in more advanced MS. What was once an intractable problem seems tractable. This has to be good news.
It is interesting that only a minority of the survey respondents support a PPMSer protest. Why?
I have previously discussed the concerns many neurologists have about the risk-benefit ratio of ocrelizumab in PPMS. Ocrelizumab is a much more potent B-cell depleter than Rituximab, i.e. ~10x as potent. A 600-mg dose of ocrelizumab is ~6x more potent than 1,000-mg dose of rituximab. This may explain the efficacy difference between the two monoclonals; particularly if ocrelizumab is targeting the hard to get to meningeal and intrathecal B cells.
After some of the comments on this blog we ran a survey to poll what pwMS thought about the ocrelizumab results. It is pretty clear that for pwMS ocrelizumab represents a real advance and the beginning of something very important for them. We now have something to build on. Let’s hope we see a large number of new trials exploring other DMTs in more advanced MS. What was once an intractable problem seems tractable. This has to be good news.
It is interesting that only a minority of the survey respondents support a PPMSer protest. Why?
CoI: multiple
Re. " It is interesting that only a minority of the survey respondents support a PPMSer protest. Why? "If it was explained what you mean by 'PPMSer protest', if it was defined more with an example on the survey this may have supported it more. What do you mean by PPMSer protest? PPMSers protesting outside a particular building? Sorry if I sound naive but I might not be the only one to think this way.
How about a march on the EMA buildings in Canary Wharf, or a PPMSer sit-in at the EU-Parliament in Brussels, or an online petition, or a PPMSer protest outside, Dowing Street? Any idea if Theresa May's mother had PPMS or SPMS?
Perhaps some PPMSers – such as I – are dismayed about the continued emphasis on immune system sledge hammers. Drugs which carry very significant risks. I'm all for "Think Hand", but not if it is primarily a vehicle to get more people taking the stuff pharma churn out. Stuff which will, for many, have a risk/benefit ratio which will have to be weighed up very carefully.In my opinion, I need neuroprotectives. Not semi-destruction of my immune system.
You are very smart. Do they expect us to believe that a drug with a 24% benefit in 44 year olds with gad+ lesions is going to work in 65 year olds with no lesions or relapses in many years? They want us to risk urosepsis over a possible marginal benefit? They must think we are idiots.
Totally agree. But then, how do you explain that 90% of voters in the survey believe that Ocrelizumab results are meaningful?I believe that this kind of surveys are a way of diffusing the responsibility of a failed treatment strategy: YOU want more immunomodulators, so WE are giving them to you. Don't say you weren't informed.Much like the papers you sign before extending your Tysabri treatment.
Wear a 'Ocrelizumab for PPMS or Think Hand, Ocrelizumab for PPMS' T-shirt for the MS Walk. More making a statement than a protest.
If I'm gonna wear a T-shirt and wave a banner around I'd rather the message 'cladribine 4 progressive MS' 'please don't forget us'
I / Person with Progressive Relapsing MS, losing mobility by the day, cannot wait for a chance to protest the lack of possibility for many / including myself, to be treated with Ocrelizumab…
Have you tried to obtain off-label cladribine?
At the end of trial, all participants should be asked a simple question:Were you taking the active drug or the placebo?This could be used as a measure of success of the blinding process and should reflect in the overall "effectiveness" of the drug.Reading again the published results of the Ocrevus trial, the drop-out rate of the placebo arm was huge, a sign that the blinding process had literally collapsed.
Interesting point. If you have an infusion reaction with the ocrevus, you know instantly that you are on the drug, so you are going to be more confident and optimistic going forward. This could easily bias the results.
In the trial they give placebo infusions for the placebo patients. This trial was double-blind so neither the nurse administering the infusion, or the patient, would know whether the active treatment or placebo was given.
Indeed. However, 40% of pwPMS had infusion related reactions versus 26% on placebo, hence "Tuesday, August 08, 2017 11:18:00 pm" probably has a little point here.
You are a complete sell out. Rituximab completely depletes b cells to undetectable levels. Hence, no drug can be "stronger." The concept of ocrevus being "more effective" or better at getting to "intrathecal or meningeal" b cells is completely made up. The data in the OLYMPUS trial for younger patients with gad+ lesions are actually better than the data in the ORATORIO trial. I dare Genentech to go head to head Ocrevus vs. rituxan. They will find that they are equivalent except possible increased risk of cancer with Ocrevus. There is no need for Ocrevus to exist in the first place. It is a complete farce, and they deprived patients with MS of anti-b cell therapy for 15 years in order to fatten their wallets.
Very good point. Ocrelizumab should not be licensed, it is a worse and more dangerous drug than Rituximab.Outlaw, permanently, drug companies, and instead use all the money currently spent filling their pockets doing government research and clinical trials.
I had Ocrevus at the start of June. I was in the clinic with two other PPMS patients who were also getting it. In the roughly two months that have passed, I am now able to walk 1160 meters at a time whereas previously I struggled to do even 400 meters. I have been able to use stairs. I have gotten out and done yard work at my house. I have been able to remember where I put my keys 5 minutes ago instead of looking for them far past the time I was supposed to leave.It was subtle at first, but after about 6 weeks it was definitely improving. All that I have done for the last 4 years is lose the ability to do stuff – with Ocrevus, I am now turning the clock back. I am hoping to start running again soon.To deny people the opportunity to take back from this thief of a disease, particularly if they can cover it themselves, just isn't right.
Ocrevus does not enter the nervous system or grow nervous tissue, so your improvement is just coincidental. Many people with MS improve spontaneously without treatment…including people with progressive MS. In the clinical trial in PPMS with Ocrevus (ORATORIO), the average patient declined rather than improved. MS is not like ALS where people tend to uniformly decline-there is a lot of variation. Also, there is an essentially identical drug in existence (rituxan), so why would someone be entitled to specifically receive ocrevus. Rituxan should be the preferred agent based on lower cost and longer safety history. Just remember: someone has to be deprived of medical care they could benefit from in order for you to get Ocrevus instead of rituxan. Do you care, or is it all about you?
There is strong evidence for remylination occuring following the removal of inflammatory burden. Evidence of people having less disability is commonly seen in trials of other high-efficacy therapies.
Fast track improvements under immunosuppression could be coincidental, but they are probably due to inhibition of more inflammation and thus reduction of swelling within the closed compartment of the skull. Which means that part of the perceived disability is caused by pressure on the axons within the inflammation site (relapse followed by remission).This kind of relief is not reversal of disability, it is just a pause of the immune reaction.For remyelination to take place, CNS debris must be collected first. Removal of the inflammatory burden by means of immunosupression won't deploy the garbage collection process and remyelination will be suppressed.