Cytapheresis as a Non-Pharmacological Therapy for IBD... in JAPAN

[Lady Organic]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083276/

'' Cytapheresis therapy which removes leukocytes from peripheral blood has first been applied in the treatment of UC in 1995 [2]. The primary aim of cytapheresis is to suppress and reduce impaired immune responses in the diseased intestine by removing circulating activated leukocytes, especially granulocytes, which have been shown to cause intestinal crypt abscess. Currently available cytapheresis techniques for active IBD patients are filtration leukocytapheresis (LCA), adsorption granulocyte/monocyte apheresis (GMA), and centrifugal lymphocytapheresis (CLA). GMA and LCA have been approved by the Japanese national health insurance policy for treating active UC since 2000 and 2001, respectively, and have been widely used as non-pharmacological and non-surgical therapeutic option for intractable UC patients. On the other hand, cytapheresis, although GMA is in the final stage for getting the government approval, has never been approved for CD in Japan.''

14 years in Japan using this treatment, why not here??? I dont get it, its too expensive for gvmt to run it? since no pharmaceutical company can intervene in this treatment, its been overlooked and brushed away? any more infos are welcomed anyone. Hopefully we have better chance with fecal transplant as a non-pharmaceutical treatment...

 

[wild_one353]

Some of your comments remind me of my initial motivations to devote much of my time looking into the science myself, i felt that if there was a natural therapy that was not able to be owned and patented by a large corporation, it would either be kept secret of or just fall by the wayside, and i could possibly find out about it on the internet. I remember thinking, are there any scientists truly representing the interests of the patient? There seemed to be endless intentions of manipulating natural processes to find drug targets, rather then using this information to find the true cause. I wanted to be that scientist that was only fully interested in finding the true cause. Now looking back, i DID end up finding almost exactly what i predicted i would find, fecal transplants. The first person to cure their Ulcerative Colitis with a fecal transplant was a scientist and that was 1989 I think. luckily it didn't fall completely by the wayside, dr borody took notice and started experimenting pushing the research forward, it has been a slow but steady advance, but the momentum now is so fast this treatment could be here in at least 3 years. Fecal transplants are here to stay.

 

[Lady Organic]

just so weird to me bc this is no longer experimental, its current treatment in Japan! I guess Japan is on another plantet...

 

[24601]

There are definitely different factors that come into play in Japan as compared with the US in terms of which treatments are researched and widely used.

I keep reading how Enteral Nutrition is still not that widely used even for children in the US and yet in Japan it's normal to use it in adults for inducing remission and even as a 50-50 diet for maintenance. I think perhaps this is another illustration of the vast differences - and of course the size of the US and their budgets for developing new therapies has an effect on all of us.

 

[Lady Organic]

Yeah I know how EN is popular in other parts of the world. I wish i could have tried it when I was first diagnosed; when we were exploring different minor therapeutic interventions, the first 2 years. I was not knowledgeable at that time and completly dependant on my doctor. Patient's knowledge about disease results in better discussion and collaboration with doctor... well, now its too late for me to give it a real try and I cant risk going off immuno-suppressant. I was in a flare last year, but it happened so brutally and I tried EEN for 2 days only. I couldnt test it any longer unfortunately. I was the first patient my GI prescribed EEN.

 

[Pilgrim]

We had a huge decrease of symptoms when my daughter was on 6 week courses of EEN. Unfortunately, in our experience, even moving to 50%EN (with a good diet for the rest) caused her to return to symptoms with no med. Also, while her symptoms reduced on EEN unfortunately her fecal cal was through the roof (1800 +).

So, it was a very good alternative to steroids but I think that people need to be monitored by fecal cal instead of just a disease activity index with EEN to make sure they don't have ongoing inflammation. We needed a maintenance med.

 

[24601]

Absolutely, EEN, like any treatment, is not always enough for an individual and as with any treatment there will always be non-responders but it's good to know it's an option! And there are too many doctors still who aren't happy to consider it as even part of the solution for their patients.

And I couldn't agree more with the need for treat-to-target protocols! I'm hoping that more doctors start to monitor inflammation since it doesn't necessarily correlate with symptoms and we really do need to know if the treatments are working.

Wishing your daughter lots of success with her treatment, Pilgrim, and the very best of health :rosette1::sun::Flower::dance::soledance:

 

[Lady Organic]

ive just watched this very encouraging story of a man fighting liver cancer originated from a rectal cancer. he was treated here and doctors didnt know any other treatment other than chemeotherapy for him. After this preliminary treatment, oncologists didnt have any other options for him. He was awaiting death. Surgery was not possible due to location of cancer. So this man made some reaseach and found a laser treatment which has been offered in Germany since 25 years! he made the trip and he''s been treated and the laser has burned his tumor. 5000$ for foreigners, free for Germans. Cost of such a medical laser equipment : 65 000$ as opposed to 100 000$ for 1 year of chemeotherapy/patient. the man had previoulsy done 3 years of chemeo, so that was 300 000$. After the low cost laser treatment, he's now in remission.

we often think we have access to all the most advanced treatments in North America, so this shows it is clearly not always true. I wish there would be a more international global approach to treatments for diseases. This story proves again that other options do exists, such as Cytapherisis for us in Japan. Other treatments do exist in other worlds and hopefully they will be more accessible for everyone in the near future.

I'd like to ear of any IBD patient from Japan who knows about Cytapherisis.

 

[wild_one353]

ive just watched this very encouraging story of a man fighting liver cancer originated from a rectal cancer. he was treated here and doctors didnt know any other treatment other than chemeotherapy for him. After this preliminary treatment, oncologists didnt have any other options for him. He was awaiting death. Surgery was not possible due to location of cancer. So this man made some reaseach and found a laser treatment which has been offered in Germany since 25 years! he made the trip and he''s been treated and the laser has burned his tumor. 5000$ for foreigners, free for Germans. Cost of such a medical laser equipment : 65 000$ as opposed to 100 000$ for 1 year of chemeotherapy/patient. the man had previoulsy done 3 years of chemeo, so that was 300 000$. After the low cost laser treatment, he's now in remission.

we often think we have access to all the most advanced treatments in North America, so this shows it is clearly not always true. I wish there would be a more international global approach to treatments for diseases. This story proves again that other options do exists, such as Cytapherisis for us in Japan. Other treatments do exist in other worlds and hopefully they will be more accessible for everyone in the near future.

I'd like to ear of any IBD patient from Japan who knows about Cytapherisis.

And some of the first fecal transplants for IBD were done in australia!!

 

[24601]

This is a treatment that I've kind of tried to keep half an eye on even after it was first put forward for Crohn's and then largely set aside. The results have never been as good for CD as for UC, although there may be some explanations for that - the samples often contained patients with more severe disease who had already failed treatment and it's not effective for small bowel Crohn's (my specialist interest!)

But it has surprised me that it hasn't been used more widely for UC (outside of Japan) since it seems that it has proven to be very useful especially when used early in the course of the disease, before exposure to lots of medications and with fairly intact colonic mucosa, and has a better safety profile than the current meds.

The benefit of using this to treat children and teenagers, especially, at initial presentation and before the first use of steroids seems clear, with the high success rates for such patients and the opportunity to avoid the side effects of steroids for such a population. I can't see a good reason why this isn't offered more widely. It really does seem shocking when you look at the stats for certain UC populations - and consider the alternative treatment path that patients face without it.

I think what i hadn't realised was that in Japan, the prevalence of UC is more than 3 times higher than that of CD - and this may go a little way to explaining why cytapheresis research gained more support in Japan. But it does seem that there must be other factors at play too.

Here's what I've read on cost:
In a comprehensive study, Panés et al[78] estimated the treatment cost for patients with UC in the EU countries for conventional medications and GMA. The average annual cost per patient treated with conventional medications was estimated to be 6740€, while the cost for GMA was 6959€, which is very close to the conventional medications. In contrast, for steroid-dependent patients, the average annual cost was 6059€ for conventional medications and 11436€ for GMA. Further, this study found that the efficacy rate in patients who achieved clinical remission with GMA was 22.5% higher than for conventional therapy. The authors concluded that incorporating GMA in the therapeutic management of patients with moderate-to-severe UC, GMA is cost-effective and the extra cost is compromised by GMA’s safety profile when compared with drug therapy. Source

And there was certainly some doubt cast about the efficacy by one of the double-blind trials, but that trial has been questioned: "Due to the obvious difficulty of carrying out double-blind randomized studies with inactive columns, results are available from only two studies of this type (one using leukocyte apheresis and one using GMA). In the leukocyte apheresis study, the response to active treatment was significantly higher than in control subjects (80% versus 33%, respectively).37 Surprisingly, in the other study, carried out in more than 200 patients treated with GMA or an inactive column,24 no significant difference was found (clinical response for 44% versus 39%, respectively). In spite of the theoretically adequate strength of the study, the large number of cases rejected during recruitment or lost to follow-up during the study, together with debatable inclusion criteria, have given rise to some doubts regarding the reliability of these results." Source

Perhaps this treatment didn't prove as useful for the steroid dependent and refractory cases as was hoped and trials into other therapies were therefore pursued instead. But the data seems clear that this is a useful and safe treatment, with especially good results early on for UC and some Crohn's. I'd really like to understand why it's not been used more!

When I was at my hospital's apheresis unit last week having my stem cells havrested, I asked them if they'd ever treated any patients for UC and Crohn's and the nurse could remember only one patient being treated for Crohn's.

Here are some studies I found:
Lots from Japan (obviously!) but this 2014 review is interesting (quoted above)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123360/
One from the US (2006, Mayo Clinic)
http://www.ncbi.nlm.nih.gov/pubmed/16378006
One from Italy
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258586/
One from Spain
http://www.ncbi.nlm.nih.gov/pubmed/18367949
One from Finland
http://www.ncbi.nlm.nih.gov/pubmed/19137602
One from Sweden
http://www.ncbi.nlm.nih.gov/pubmed/17327942
Two from Germany
http://www.ncbi.nlm.nih.gov/pubmed/20331579
http://www.ncbi.nlm.nih.gov/pubmed/16437606
And I think this was one of the original studies from Japan
Shimoyama T, Sawada K, Tanaka T. Granulocyte and monocyte apheresis with the G-1 column in the treatment of patients with active ulcerative colitis. Jpn I Apher. 1999;18:117–131

 

[Lady Organic]

thank you 24601!

this is so interesting!

ive just read the first article so far and keep the rest for later. I am pleased to see the treatment is been used in Europe too, so that means it must be somehow possible to try it. Im definately going to inquire about that. eventhough I dont fit the ideal candidate criteria, I still have nice mucosa without any scarring. so maybe for a case like mine of long term duration of disease (long moments of remission too), multiple treatments including steroids, the chance of success could be around 50% im guessing.

its funny because ive already done acupuncture and a few time they did a bloodletting on my finger (to help arthritis). I imagine the quantity of blood remove in the present techniques are more elaborated somehow. I wonder how is the procedure done exactly, but Im prolly going to read it in one of the articles you posted. thx again!

 

[24601]

Yes, I would think you might well still fit in the 50% category. I'm still a little unsure if the 50% results are what they refer to as 'disappointing' since that still seems really useful - especially in patients who don't respond to any other medical treatment. It wouldn't seem to make sense to call that disappointing when there a drug trials that are touted as promising etc. with, I think, lesser results.

My understanding of the procedure is that they put in a large canula in one arm and this takes the blood away to the filtration machine with the adacolumn (or similar), the blood is filtered removing the inflammatory components and returned via a canula placed in the other arm. That's basically the procedure I had last week for stem cell harvest - except they filtered out stem cells obviously! And collected a little plasma too for storage. There were other patients having apheresis treatments for other diseases and the procedure looked the same (same setup with the canulas, tubing and machine) but the bags of blood products were different - for some they were filtering out large quantities of plasma for example.

As i understand it, the protocol for inducing remission is something like 1 one-hour treatment per week for, if I remember correctly, five weeks. Or at least I think that might have been the original protocol. But there are another 'intensive' protocols with two treatments per week, either for the first 2-3 weeks or the entire treatment length, and they've looked at different durations of treatment, perhaps up to 11 weeks. If patients have no response in the first few weeks then they may be classified as non-responders and treatment stopped. Some studies found 90 min sesions more effective. And some found it better to process more blood per session - 3000ml vs. the conventional 1800ml.

Meeting people who are routine visitors to the apheresis unit, some who go back twice a week every fortnight for their treatment, made me think of this treatment for IBD again but as far as I know it's not used in the UK. I plan on asking my GI why that is! I'll be asking just out of curiosity, because it's not appropriate for me, I don't believe, but it seems a shame it's not an option for others.