Anti-inflammatory Effects of SCIG?

[Remy]

Hi all - 

I'm new here...a Google search led me to the old post below by terryhalper.

I'm currently dealing with CVID and an autoimmune disease.  My doctor is considering using my regular SCIG monthly instead of weekly to better approximate the higher doses given IVIG for autoimmune disease.  I'm looking for information supporting this change to better guide our decision making.

It concerns me that studies may have shown that one may lose the anti-inflammatory benefits when administered subQ.  Does anyone have any references to the studies mentioned here?

My understanding is that while US dosing recommendations suggest increasing the dose when switching from IVIG to SCIG, European doctors typically have switched at 1:1 with no loss of benefit.  Any thoughts here?

Thanks!
Remy

Hi John,

There are 2 things I have heard that have prevented me from making the change from IGIV (I am on Flebogamma for the last 8 years. Other brands of IGIV starting in 1991), to subq gammaglobulin products:

1). It takes 25% more product to achieve the same therapeutic results with subq vs IV infusion. This may not be a concern for those of you in the UK, but for those of us in the U.S.A. who pay part or all of the substantial costs out of pocket, it is definitely a consideration.

2). I believe studies have also shown (I'll try to find and cite them) that one may lose the anti-inflammatory benefits of IGg products when administered subq vs IV routes. Since inflammation is a major cause of cancer, and CVID patients are particularly prone to certain cancers (stomache, thyroid, GI tract), I have decided against this somewhat appealing, subq administration of IGg.

In addition, I understand that subq (sub-cut, as you call it), requires multiple weekly sessions of several hours each, vs my once every 28 day 5 hour regimen with my nurse. I prefer to go with the once a month and done IV and "pretend" I am "normal" the other 27 out of 28 days. Everyone needs to make their own decisions of course in consultation with their physicians to determine what is best for their own unique situation.

I hope this information is helpful in giving you food for thought on your decision.

I generally follow ==> "If it ain't broke, don't fix it".

Terry

Read more: primaryimmuno.proboards.com/thread/510/any-hizentra-tips#ixzz3j5GGMxEg

[s162216]

Aug 17, 2015 14:54:32 GMT Remy said:

Hi all - 

I'm new here...a Google search led me to the old post below by terryhalper.

I'm currently dealing with CVID and an autoimmune disease.  My doctor is considering using my regular SCIG monthly instead of weekly to better approximate the higher doses given IVIG for autoimmune disease.  I'm looking for information supporting this change to better guide our decision making.

It concerns me that studies may have shown that one may lose the anti-inflammatory benefits when administered subQ.  Does anyone have any references to the studies mentioned here?

My understanding is that while US dosing recommendations suggest increasing the dose when switching from IVIG to SCIG, European doctors typically have switched at 1:1 with no loss of benefit.  Any thoughts here?

Thanks!
Remy

Hi John,

There are 2 things I have heard that have prevented me from making the change from IGIV (I am on Flebogamma for the last 8 years. Other brands of IGIV starting in 1991), to subq gammaglobulin products:

1). It takes 25% more product to achieve the same therapeutic results with subq vs IV infusion. This may not be a concern for those of you in the UK, but for those of us in the U.S.A. who pay part or all of the substantial costs out of pocket, it is definitely a consideration.

2). I believe studies have also shown (I'll try to find and cite them) that one may lose the anti-inflammatory benefits of IGg products when administered subq vs IV routes. Since inflammation is a major cause of cancer, and CVID patients are particularly prone to certain cancers (stomache, thyroid, GI tract), I have decided against this somewhat appealing, subq administration of IGg.

In addition, I understand that subq (sub-cut, as you call it), requires multiple weekly sessions of several hours each, vs my once every 28 day 5 hour regimen with my nurse. I prefer to go with the once a month and done IV and "pretend" I am "normal" the other 27 out of 28 days. Everyone needs to make their own decisions of course in consultation with their physicians to determine what is best for their own unique situation.

I hope this information is helpful in giving you food for thought on your decision.

I generally follow ==> "If it ain't broke, don't fix it".

Terry

Read more: primaryimmuno.proboards.com/thread/510/any-hizentra-tips#ixzz3j5GGMxEg

Hi Remy,

Terry was last on the forum a couple of weeks ago, and I know he doesn't tend to visit too often so it may be a while before he sees your message.

I assume it's a typo when you say that your doctor is considering giving your SCIG monthly, as the volume you'd have to have would be tremendous and I doubt there would be enough sites on your body to support that much!

Subcutaneous administration (of any medicine) has a serious disadvantage over IV in that there is a limit on how much you can infuse: with IV the drug obviously is immediately in the bloodstream so there's no absorption time and very large quantities can be given in a short space of time. With SC though, you have to wait for the drug to be absorbed into the bloodstream from the subcutaneous tissues, and obviously there is only so much that the surrounding tissues can take before they are "full" and anything extra will leak out. Imagine turning a tap on to fill a tank: with IV the pipe is directly going into the tank, but with SC you're filling up a sink with a small plughole that flows into the tank. As the plughole limits the rate at which the tank can fill, the sink can eventually overflow if too much is put in.

The solution obviously is to either have more infusion sites or more frequent doses; obviously both of those have their limitations as well. Another direction is to artificially increase the volume that the subcutaneous tissues can hold via pharmacological means (this has been done for decades with subcutaneous anesthetics for instance, but the products used were unsuitable for long term use as they were obtained from animal sources and were associated with reactions), and recently a new Ig product called Hyqvia has come on the market which uses a recombinant human product (artificially produced via molecular biology, like with human insulin or growth hormone) for this. With this, prior to the Ig you subcutaneously infuse a quantity of recombinant Hyaluronidase to temporally increase the volume that the surrounding tissue can hold, and then infuse the Ig. This allows a SC infusion every 3 weeks, as the tissues can hold the massive quantities, but there are drawbacks to this as it is very new and of the few people in the UK who I know have tried it, at least 1 has already gone back to weekly SCIG. Try looking it up if you want more information as it may be suitable for you.

Weekly SC does have a tremendous advantage in that adverse effects are usually much reduced due to the lower peak level that you get immediately after the infusion compared to IV. Regarding this issue with anti-inflammatory effects though, I'm unsure. I don't know what studies Terry is referring to, and you'll have to wait until he chimes in with them, but I've had a quick look around Pubmed and not been able to find any immediate papers that are saying there is any reduction in efficacy. From the very limited amount I could find (papers which are exclusively about anti-inflammatory effects are rare compared to those on PID), if anything most are saying that IV and SC infusions are comparable when used in auto-immune conditions, and most patients actually prefer the SC as they tolerated it better. Be aware though that for most conditions where IgG is clinically recognized as effective (the list is actually surprisingly small - beneficial, clear effects have only been demonstrated in a a few conditions compared to what some claim; the list is near endless despite very little if any research into the great majority), a lot of them (especially in auto-immune conditions) are based on a short term high dosage (e.g 5 days of infusions a month) use rather than long term.

The US dosing recommendations stem from the regulatory authorities concern that SCIG may not be as effective when given 1:1 as it has lower bio-availability than IVIG - the product is being slowly absorbed and takes longer to reach peak concentration. The FDA recommend a 137% dose adjustment to compensate for this, but that is quite a general figure as the limited number of studies in this area seem to indicate that it is necessary with some patients, but not others; it's like anything in science/medicine, actual biological organisms will never fit neatly into a category due to inherent variations. One paper which looked at this in detail ended up recommending a dosage adjustment only for those where levels on IVIG had previously been unstable and/or the benefit of the IVIG had been only been of variable effect.

If you want me to provide a reference list for what I found, I'll happily post it.

Sam (Admin).

N.B, I have BSc in Pharmacology in case you're wondering why I happen to know about pharmacokinetics (what the body does to a drug). Still though, I'm not a medical doctor and you should ask one if you want detailed personal medical advice regarding yourself and your condition.

[Remy]

Aug 23, 2015 16:55:49 GMT s162216 said:

I assume it's a typo when you say that your doctor is considering giving your SCIG monthly, as the volume you'd have to have would be tremendous and I doubt there would be enough sites on your body to support that much!

No, it's not a typo!  I'm currently infusing 12g of Hizentra weekly.  I've been on it for almost 3 years now.  We are considering switching to 12g five days in a row, once monthly.  

There has been some research done on infusing Hizentra every two weeks and that was found to be as effective as weekly.  So hopefully monthly administration will be as well.  I can't see why it would be any different honestly.

If it works out in my trial, I may think about switching to Hyqvia in the future but since I tolerate Hizentra pretty well and administration is a snap by now, I'm hesitant to change formulas.

Aug 23, 2015 16:55:49 GMT s162216 said:

Weekly SC does have a tremendous advantage in that adverse effects are usually much reduced due to the lower peak level that you get immediately after the infusion compared to IV. Regarding this issue with anti-inflammatory effects though, I'm unsure. I don't know what studies Terry is referring to, and you'll have to wait until he chimes in with them, but I've had a quick look around Pubmed and not been able to find any immediate papers that are saying there is any reduction in efficacy.

I couldn't find any studies stating this either. I hope he does chime in because I'm really curious to know what he's found.

Thanks, Sam, for your reply.  I appreciate the information and your help!


Remy

[s162216]

Aug 29, 2015 20:40:32 GMT Remy said:

Aug 23, 2015 16:55:49 GMT s162216 said:

I assume it's a typo when you say that your doctor is considering giving your SCIG monthly, as the volume you'd have to have would be tremendous and I doubt there would be enough sites on your body to support that much!

No, it's not a typo!  I'm currently infusing 12g of Hizentra weekly.  I've been on it for almost 3 years now.  We are considering switching to 12g five days in a row, once monthly.  

There has been some research done on infusing Hizentra every two weeks and that was found to be as effective as weekly.  So hopefully monthly administration will be as well.  I can't see why it would be any different honestly.

If it works out in my trial, I may think about switching to Hyqvia in the future but since I tolerate Hizentra pretty well and administration is a snap by now, I'm hesitant to change formulas.

Aug 23, 2015 16:55:49 GMT s162216 said:

Weekly SC does have a tremendous advantage in that adverse effects are usually much reduced due to the lower peak level that you get immediately after the infusion compared to IV. Regarding this issue with anti-inflammatory effects though, I'm unsure. I don't know what studies Terry is referring to, and you'll have to wait until he chimes in with them, but I've had a quick look around Pubmed and not been able to find any immediate papers that are saying there is any reduction in efficacy.

I couldn't find any studies stating this either. I hope he does chime in because I'm really curious to know what he's found.

Thanks, Sam, for your reply.  I appreciate the information and your help!


Remy

Oh! From how you put it I assumed that you were proposing having it in one go, which would probably not be advisable for the reasons I gave above. Having multiple doses spread over several days is normal practice with high dose IgG (usually a full dose everyday for 5 days, then wait 5 days then repeat if needed) that is used for treating Gillian-Barre syndrome, haemolytic disease of the newborn etc as you want that intensely high level maintained. I've never heard of anyone using multiple days for PID treatment though, likely as the volumes needed are much smaller so they can be done in one infusion and that intensely high level is unwanted (as it's frequently associated with reactions).

Hizentra can be given every 2 weeks, but it's more commonly given weekly as, except for those on smaller doses, the volume is usually too large for most people to cope with without having to have excessive numbers of infusion sites and/or very long infusion times. Newer more concentrated products do make it easier as the volume is hence smaller, but the longer it gets between infusions increases the chance of a "dip" in levels when it gets closer to the next infusion - like with IVIG which can cause problems with tiredness and increased risk of infection in some people. Weekly dosing is actually a huge advantage of SCIG as it allows very constant levels to be maintained.

I don't see why you couldn't have it like you propose, but you could run into the problem of running out of infusion sites. Subcutaneous tissue needs time to recover after being infused into - like with long term diabetics (such as me!) for instance who get problems if a site is overused - and by having it every day for 5 days I could see you running into that problem unless you perhaps kept the needles in (which I don't see why you couldn't do if the pump was properly disconnected; I have a subcutaneous insulin pump and an SC cannula permanently in which I change and rotate the site of every 2 days), but I don't know if that would be possible. Plus it'll be very inconvenient for you to have to do it for 5 days every month.

There is another recent technique that you might want to look into, Rapid Push administration. Basically every 1-2 days you manually inject (with no pump) a small dose of IgG subcutaneously. This allows very stable levels to maintained, and is very quick to do each day. At the moment it's starting to gain much popularity in Canada as there's currently a shortage of SCIG pumps; the idea came about 10 years or so ago, but at the time wasn't really practical as the products available were not of a high enough concentration for the injections of to be of a reasonable volume. As that problem has now been bypassed it's becoming quite popular in some centres, and in a few studies more patients actually preferred it to having to use a pump (if you want the references I'll have to look them up again as it was a while ago I read the papers).

I hope that everything works out for you, no matter what direction you choose to take.

Sam.

[aryani]

Hi Sam,

Rapid Push Administration sounds like 'popping a pill a day', but it is probably more like injecting insulin. It sounds very promising to me. SCIG didn't work out for me (I had an allergic reaction), but this may be a solution. So it would be great, if you would be able to post more information or references.

And Remy: Just as Sam, I hope you'll find a good solution.

Aryani.

[s162216]

Sept 15, 2015 13:17:41 GMT aryani said:

Hi Sam,

Rapid Push Administration sounds like 'popping a pill a day', but it is probably more like injecting insulin. It sounds very promising to me. SCIG didn't work out for me (I had an allergic reaction), but this may be a solution. So it would be great, if you would be able to post more information or references.

And Remy: Just as Sam, I hope you'll find a good solution.

Aryani.

Hi,

There are a number of papers about rapid push SCIG around, but most are behind a paywall or I can only get to them through my university (I've just started doing a Research Masters in Pharmacology at the University of Strathclyde, which does give a huge perk!). The abstracts to quite a few are helpful though, and there are a few open access papers so if you come back shortly I'll have posted a few links up.

Sam.

[aryani]

Hi,

I found this (with dr. Google):

-articles:
www.ncbi.nlm.nih.gov/pubmed/23806460
www.uptodate.com/contents/subcutaneous-and-intramuscular-immune-globulin-therapy/abstract/45

- you tube:


I have discussed it with my specialist. It's a bit risky in my situation, because I had an allergic reaction to SCIG. I'll stick to IVIG.

Aryani.

[s162216]

That's it aryani heres another full, open access paper that's quite good. You should be able to directly access it at this link: link.springer.com/article/10.1007/s10875-009-9352-2

What do you think to rapid push? Obviously how frequently and how much you have will vary between each person, but do you think it would work out for you?

Sam.

O.K, sorry I didn't see your edit you made, perhaps it was just the product that you were using, there are other SC infusion products around, although it does vary around the world with there being something like 5 or 6 licensed in the UK, but only 3 in the USA for example.

[mothergoose]

I live in Canada, I watched the video above, that is exactly how I was taught to do my SCIG treatments, I was told I could infuse my dosage all at once or a bit every day just as long as I had it all infused in 7 days. To begin with I was told to push 1 ml in every 3 mins, I was also told after a month I could try to pus it in faster.
I was also told I could get the needle in a newer type that you can put in and leave it in for 5 days at a time, theses were quite a bit more expensive to buy.
So I do know the Push method works for at east Hizentra.
After a month or so I bought my own pump, it's just easier, I set everything up sit back and relax, I do change sites once per treatment so I use 2 sites.