Plasma exchange and disability ECTRIMS abstract

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Plasma exchange and disability ECTRIMS abstract

Postby dignan » Sat Oct 13, 2007 9:25 am

These results blow me away. This is the part I'm referring to:

Improvement in disability with PE occurred in 217 of the 271 pts (p < 0.0001). Ten percent of the pts improved by 2.5 steps on EDSS, 25% by 1.5, 50% by one and the rest less than one. This improvement was well sustained at 6-year follow up (p < 0.001) and stabilized during the years 7 to 9. From years 10-25, the pts started to worsen on EDSS but at a much slower pace than prior to PE (0.07 EDSS decline per year post PE vs. 2.6 per year prior to PE). This difference was significant, p < 0.001.




Sustained long-term improvement in disability with plasma exchange in patients with worsening multiple sclerosis: results of a 25-year follow-up study

B. Khatri, M. McQuillen, S. Tarima, M. Dukic, J. Kramer (Milwaukee, Palo Alto, USA)

Background: Plasma exchange (PE) is an effective therapy for Multiple Sclerosis (MS) patients (pts) who continue to worsen despite cortico-steroid therapy (CST) (Weinshenker B et al, Ann Neurol, 1999). A double blind controlled study proved PE to be significantly effective in reversing disability in chronic progressive MS patients (Khatri et al, Neurology, 1985). This study reports long-term follow-up results in pts with worsening MS treated with PE over the past 25 years at our center.

Methods: Worsening MS pt having failed CST were offered PE. Verification of worsening on Extended Disability Status Scale (EDSS) by at least one step by the insurance carriers was crucial in their authorization of PE. Authorized pts received weekly PE for 10 weeks and then in a declining frequency until clinically stabilized. Temporary radial artery catheterization, femoral vein catheterization or peripheral venous access was used for vascular access.

Results: 271 pts received PE. Age range 19-70, median 41: duration of disease 1-36 years, median 7; severity of disease (EDS) 3-9.5, median 6.5; 74% female; number of PE 3-227, median 20. Peripheral venous access was adequate in 70% of pts and temporary radial artery or femoral vein catheterization in the rest. None required indwelling central line placement for vascular access.

Improvement in disability with PE occurred in 217 of the 271 pts (p < 0.0001). Ten percent of the pts improved by 2.5 steps on EDSS, 25% by 1.5, 50% by one and the rest less than one. This improvement was well sustained at 6-year follow up (p < 0.001) and stabilized during the years 7 to 9. From years 10-25, the pts started to worsen on EDSS but at a much slower pace than prior to PE (0.07 EDSS decline per year post PE vs. 2.6 per year prior to PE). This difference was significant, p < 0.001. Clinical predictors of better response to PE were greater magnitude of worsening 2 years prior to PE ( p<0.001) and duration of disease less than 7.8 years (p<0.001) A total of 8709 PE procedures were well tolerated without any major side effects.

Conclusion: PE can bring about significant and long lasting improvement in disability in worsening MS pts. PE is safe. The large number and types of MS pts selected, the magnitude of improvement and most importantly, the duration for which the improvement persisted, highlights the importance of our findings.

ECTRIMS link
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Plasma exchange

Postby lyndacarol » Sat Oct 13, 2007 11:39 am

I know that plasma exchange (also called plasmapheresis) is a non-selective process. It is thought to remove antibodies, but known to remove calcium as well. My question is "What else?" Insulin maybe???

Perhaps this process shows an improvement until the pancreas churns out excess insulin again?

It is a common treatment for myasthenia gravis (MG), another "autoimmune" disease, which a friend had. Her treatment cost $5000 a pop 8 years ago. (She had plasmapheresis every other day for two weeks and it gave only temporary improvement.)
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Re: Plasma exchange and disability ECTRIMS abstract

Postby Lyon » Sat Oct 13, 2007 1:14 pm

dignan wrote:These results blow me away.
Sustained long-term improvement in disability with plasma exchange in patients with worsening multiple sclerosis: results of a 25-year follow-up study


Very interesting. Thanks dignan.

I guess I can "kinda, sorta" understand the short term results, but the long term results defy me.

I guess I need to learn what plasma consists of, how and where plasma is generated in the body and what exactly "Plasma Exchange" consists of.

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Postby dignan » Sat Oct 13, 2007 2:16 pm

Maybe I'm going off half-cocked here, but isn't a study following 271 patients for 25 years that gives overwhelmingly positive results on disability progression with p values <0.001 enough to make this the standard of care for ALL MS patients with worsening disability?!?! Since it's already an approved treatment, no phase 3 trial required, just start using this treatment on a lot of people, right now. Somebody tell me why I'm wrong!
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Plasma exchange

Postby lyndacarol » Sat Oct 13, 2007 3:44 pm

Dignan, you are RIGHT ON on every point!!!
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Postby Lyon » Sat Oct 13, 2007 5:06 pm

dignan wrote:isn't a study following 271 patients for 25 years that gives overwhelmingly positive results on disability progression with p values <0.001 enough to make this the standard of care for ALL MS patients with worsening disability?!?!
Not to be purposely cynical, but also not wanting to avoid what might be the truth of the matter......if a large drug company stood to profit from this you can bet that negotiations and/or pressure would have already started being put on the insurance companies to accept the treatment and pay for it, in addition to their long ago "leaking" information about the results to the media to raise general awareness.

I don't know enough about this specific "Plasma Exchange" situation to be confident that it really is the greatest thing since Carter's little liver pills, but this situation might be a good lesson for us that maybe good things really can slip under our radar and that really good things might not gain the immediate recognition and acceptance we had long assumed it would.

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Postby thinkingoutloud86 » Sat Oct 13, 2007 5:29 pm

The way this study comes across, my initial reaction was "where has this been all of this time"...I did a little google search and found some more info produced by mayo on it (see below). Does anyone have more info on the risks or side-effects?

New Mayo Clinic Study Demonstrates Patients' Multiple Sclerosis Lesion Type Dictates Effective Treatment
Plasma exchange treatment shown most helpful for severe attacks in subtype of MS patients

Thursday, August 11, 2005

ROCHESTER, Minn. — A Mayo Clinic study demonstrates that only those multiple sclerosis (MS) patients with evidence for antibody deposition or complement activation — immune cells that can cause tissue destruction — in their lesions are likely to respond to plasma exchange, a treatment for acute MS attacks. This is the first evidence that differences in pathological subtypes of MS may predict response to treatment. The findings will be published in the Aug. 13 issue of The Lancet.

"The new findings may partly explain why some patients respond to a particular treatment and others do not," says Claudia Lucchinetti, M.D., Mayo Clinic neurologist and the paper's senior and corresponding author. "The biological basis for the variable response to current MS treatments is not well understood. It may be that not all MS patients form lesions in the same way and therefore would not be expected to respond to a given treatment the same. Thus, MS treatments may need to be more individualized and tailored for different types of patients."

During plasma exchange treatment, the patient's blood is removed and the blood cells are mechanically separated from the fluid plasma. The patient's blood cells are then mixed with replacement plasma and the mixture is returned to the patient. Mayo Clinic MS experts including Moses Rodriguez, M.D., Brian Weinshenker, M.D.; and Mark Keegan, M.D.; previously found plasma exchange may help restore neurological function in approximately 45 percent of those experiencing sudden, severe MS attacks whose resulting disabilities did not respond to high doses of steroid treatment.

Dr. Keegan, first author of the study, points out that plasma exchange is a treatment for severe MS attacks when standard treatment with corticosteroids fails; it is not a treatment to suppress future attacks or to restore neurological function that has been absent for more than three months.

The study was conducted retrospectively in an attempt to unravel the "all or none" response Mayo Clinic MS experts had witnessed with plasma exchange treatment for acute attacks in 19 patients who at one point had undergone a brain biopsy in the course of their disease when the diagnosis of MS was still in question. Patients were seen at Mayo Clinic, the University of Vermont or a European center, and all included in the study had severe disabilities, including paralysis and loss of speech, which failed to improve with standard anti-inflammatory steroid treatment. Since tissue was already available on these patients, Dr. Lucchinetti and her team classified their lesions into four patterns based on the types of immune cells present and the pattern of myelin injury. Previously, Dr. Lucchinetti and her European collaborators, Professors Hans Lassmann of the Brain Research Institute at the University of Vienna, Austria; and Wolfgang Bruck of the University of Gottingen, Germany; developed and described a classification system for MS patients by lesion type into patterns I, II, III and IV. The investigators found that the 10 patients with pattern II MS lesions which contain large quantities of immunoglobulin (proteins that serve as antibodies) and complement activation (the ability to combine with antibodies to destroy tissue) experienced moderate to marked improvement after treatment with plasma exchange. These patients experienced major gains in cerebral, motor, brain stem/cranial nerve, cerebellar and/or sensory function. Improvement began after an average of three days. However, none of the MS patients with lesions typical of either patterns I or III, which lack evidence for antibody or complement activation, achieved such improvement.

The investigators postulate that only the pattern II MS patients' attacks responded to treatment because of the way in which plasma exchange works — by removing disease-causing factors in the blood and plasma, such as antibodies and complement, which are only present in pattern II MS lesions.

The findings published in The Lancet validate a theory held by Drs. Lucchinetti, Lassmann and Bruck that there are distinct patterns of tissue injury in different MS patients — that MS is not the same disease in all patients and therefore cannot be treated the same way in everyone.

"Our work suggests that the development of MS may vary from patient to patient," says Dr. Lucchinetti. "This recent data on the correlation of plasma exchange response to tissue pathology supports our hypothesis that different patterns of tissue damage in MS may require different treatment approaches."

However, brain biopsies such as those undergone by the patients studied are not routinely done in MS patients — they are only performed when excluding another diagnosis such as tumor or infection, according to Dr. Lucchinetti. Therefore, she explains that it is necessary to identify specific markers. either from blood, DNA or MRI, which can distinguish between these four patterns without the need for a brain biopsy.

Dr. Lucchinetti is the principal investigator of the International MS Lesion Project, funded by the United States National Multiple Sclerosis Society since 2000. This project is focused on trying to identify clinical, MRI, blood or genetic markers of MS lesions which could be used to stratify MS patients into subgroups in order to better tailor their treatments to the ways in which their MS lesions are formed.

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Postby dignan » Sat Oct 13, 2007 6:18 pm

That article about lesion types rings a bell. At first I thought they were just looking at lesions, so I was going to say that it doesn't really matter based on the ECTRIMS study, which is impressive for the results on disability progression, not on lesion formation. Anyhow, after reading the article you posted, it sounds like they are saying that the overall response to plasma exchange is better in type II lesion patients. Which then leads me to think, if it is only people with one type of lesion who respond, wouldn't the results from the ECTRIMS study be even more impressive if they could break it out by lesion type? Wouldn't their study include a relatively large number of non-responders? Do our neurologists know which lesion type we are based on our MRI scans? Do you need a special type of scan?
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Postby Lyon » Sat Oct 13, 2007 6:25 pm

I'm not sure what's going on. I searched "plasma exchange multiple sclerosis" at the Mayo Clinic site and now it seems they are pointing out that it only works in some MS patients and even then for only three months http://www.mayoclinic.org/medical-edge- ... jan-1.html

This is my attempt to send the results of the search http://tinyurl.com/2mqvbl

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Postby dignan » Sat Oct 13, 2007 7:20 pm

Bob, I think this all means that the ECTRIMS study challenges the traditional notion that plasma exchange is just good to help get over relapses and nothing more. And I'd say it presents one hell of a challenge.
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Postby Lyon » Sat Oct 13, 2007 7:57 pm

Hi dignan,

I don't know the process for writing things up at ECTRIMS but maybe these researchers just weren't as cautious in their wording as the other authors of articles regarding MS plasma exchange?

A challenge? I suppose if the authors were convinced that plasma exchange is an infrastructure which could be improved enough to show improvement for the majority of MS patients and provide them long term improvement, but so far no obvious reasons for such beliefs have shown themselves.

Please notice the PM I sent you.

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Postby marcstck » Sat Oct 13, 2007 11:34 pm

Just thought I'd chime in with my personal experience. I underwent six rounds of plasmapheresis this past July in a "Hail Mary" attempt to put the brakes on my PPMS. Sorry to report, the treatments did nothing, and were quite grueling at that. Each exchange was a minimum two to three hour long process, sometimes longer, and after each treatment I was hit with tremendous physical exhaustion. I did the treatments over the course of two weeks, and would barely recover from having one treatment when I had to undergo the next. Of course, it would have been worth it had the results been better, but as I stated previously at best the treatment did nothing, at worst it left me weaker than before I started...

Of course, this is not to say that my experience is typical across the MS spectrum. But the folks that were administering the treatment did say that the best results were seen in relapsing remitting patients who were undergoing severe acute symptoms. As I am most definitely progressive, this was a speculative treatment at best, and was done partially in an attempt to see if I might be responsive to Rituxan, which also reduces or eliminates most of the antibodies in the blood stream. As I didn't respond to the plasmapheresis, my doctors are thinking I will not respond to Rituxan...
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Postby Lyon » Sun Oct 14, 2007 12:03 pm

Thanks for the info Marc. Evidently they've been seeing reduction in disability but you can't count on that.

Are you quite sure that plasmapheresis might have stopped progression of disability even though you didn't notice a reduction in symptoms?

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Postby marcstck » Mon Oct 15, 2007 2:22 pm

My disease progression has definitely continued unabated since I underwent plasmapheresis. Rather than see a reduction in disability, my condition has worsened.

I had high hopes for the treatment going in, but unfortunately my expectations were not met. I certainly wouldn't take my negative experience to mean that plasmapheresis is worthless for all multiple sclerosis patients, but despite this recent study most research on the subject states that only a small subset of MS patients will be helped by the process.
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Postby Lyon » Mon Oct 15, 2007 3:37 pm

marcstck wrote:My disease progression has definitely continued unabated since I underwent plasmapheresis. Rather than see a reduction in disability, my condition has worsened.
I am SO sorry to hear that, but thanks for sharing it.

There have been similar accounts regarding MS symptoms minimizing during pregnancy and "making up for it" afterwards and accounts of more rapid progression after stopping Tysabri.

That almost seems to defy logic but logic has it that a cold shower would cool you off on a hot day when in reality it turns your metabolism on high which actually makes you feel hotter afterwards. I have great respect for logic and I think it needs to be used a lot more in the world of MS research, but it's also obvious that we can't have blind faith in logic alone.

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