Current thoughts on clinical trials and other treatments (Dr. Li or Stanford OIT

[hk]

We got dd's lab results back today and everything went up (not that there is much difference in a RAST score of 70 when it was 30 last year).  We had investigated and ruled out doing a multi allergen clinical trial at Stanford a few years ago.  The newest test results and the fact that she's 10 now have me wondering if we made the right decision.  I think we did as our allergist strongly cautioned us to avoid the Stanford study as he thinks their protocol is too aggressive and that they under treat reactions.

We have also considered seeing Dr. Li in her private practice, but it is 3000 miles from us. I would do it though.

I'm just curious where the members of this board are at in their thinking about OIT or TCM these days?  I always value your opinions.  I'll probably be over this phase in a day or two.  Today I feel like I have to do something!  Thank you!

[hedgehog]

DS goes for his two-year follow up appointment this week.  I am so happy we did it.  It makes a world of difference to us.

http://www.nefoodallergy.org

[lakeswimr]

We started desensitization at the same place Hedgehog used.  So far so good.  I am glad we are doing it.   They are claiming a 95% success rate.  They are not calling it a trial but desensitization. 

I think they worked out a lot of the kinks that they didn't know at first.

They advise people to not do any exercise two hours after they eat their daily dose.  They are not supposed to take a hot shower or bath and hour before or two hours after.  They are not supposed to take Motrin with their dose.  They are supposed to eat carbs just before and right after their dose. 

They found that when people didn't follow these guidelines people were more likely to react. 

They also found that many people have minor reactions like an itchy mouth or a stomach ache. 

I think and hope I made the right choice for my child. 

[LinksEtc]

I'm pretty sure you've already seen this thread, but I'll link to it to be sure.

Desensitization Programs in the US -- OIT SLIT SCIT

If you work your way backwards, you'll see some recent stuff.

The gurus are still cautioning that OIT is not ready for clinical practice.

[lakeswimr]

I think it depends on which 'gurus' you ask.  Mendelson is certainly in the guru category and he is one of the allergists at NE FA clinic where we are going. 

[lakeswimr]

Hedgehog,

How high of a daily dose did you get to?  I was surprised they said they now try to get people up to 15/day rather than 1-3 a day because it helps protect against reactions better.  That's a heck of a lot of peanuts!

Did you have any minor reactions along the way?  So far we haven't.

[LinksEtc]

No disrespect intended towards Dr. Mendelson. 

I guess that I agree with Dr. Wood & Dr. Sampson that further research is needed for OIT.  These docs are extremely knowledgeable and I think it's important for any newbies reading threads like this to be aware of what these docs think about this issue.

Working with my dd's docs, I am often willing to push limits and take risks (& aggressive approaches) in managing my own dd's multiple health issues ... but I guess my public posting style is somewhat conservative because I know there are many with limited medical knowledge reading.  Newbies especially may not understand the very real risks involved or that those docs who feel OIT is ready for clinical practice are currently in the minority of docs.



http://www.jaci-inpractice.org/article/S2213-2198(13)00457-1/fulltext

http://www.asthmaallergieschildren.com/2012/05/11/oral-immunotherapy-for-food-allergy-not-ready-for-prime-time/

[ajasfolks2]

When we see our allergist in next couple of weeks, I'll again ask his opinion about OIT.

Most NOVA docs are still saying "not for prime time" as I understand it from other folks in area.

[CMdeux]

 


There is also apparently some thought that not ALL patients will respond well to OIT-- and there is currently not a lot to separate who will from who won't.   There is VERY real risk associated with OIT-- and while the percentage is a mystery since too few people have gone through well-controlled trials-- there seem to be several groups of patients in terms of responders to OIT:

1) those who establish TOLERANCE-- for real tolerance, as in 'we forced this person to no longer be allergic to this allergen.'

2) those who establish an INCREASED THRESHOLD which is STABLE-- as in, anaphylaxis is very unlikely as long as the person maintains that threshold via regular consumption, probably for good. (though again, nobody is sure)

3) those who drop out because they can't seem to establish a STABLE threshold even for dosing beyond very low levels-- these are the anaphylaxers in the treatment group, and

4) those who move unexpectedly from groups 1 or 2 to group 3-- sometimes AFTER treatment, sometimes DURING, sometimes only during illness or other immune stress, sometimes for no reason that can be determined.  The problem is that even coming in allergic to specific allergen proteins, or at low threshold doses.... well, none of that seems to be a determining factor.  The problem is that there ISN'T a way to know that it will/won't happen to a particular patient until you try it.  The other dark side is that there seems to be a very slim, tiny minority whose thresholds are made WORSE (lower) by exposure, or who develop other IgE-related disorders.    Well, actually the EoE group isn't such a tiny minority.   

[lakeswimr]

What we were told is that about 1-2% of people have serious reactions during treatment.  Many people have minor reactions.  They do not encourage people who have had the most severe of reactions to do desensitization.

One of the allergists there said he was in the ICU from a nut reaction and so does not think the treatment would work for him. 

I don't know how many people have to go through their program before that would be enough to make people feel the program has things down.  I can't remember the exact number but I think they are now at somewhere over 430 people who have gone through the program. 

As I said, they found a lot of the causes of the sudden reactions.   They were from people doing things that caused a rise in their metabolism such as exercising after a dose, taking a hot bath or shower one hour before or two hours after a dose, taking Motrin with a dose, not eating carbs just before and right after eating it, being in hot weather, etc.  Once those things are eliminated from what they are telling me people are not having reactions.  Almost all reactions were in cases where people did some of the above things.  Also, they used to get people up to 1-3 peanuts a day and now they aim to closer to 15/day because they find that people don't have unexplained reactions when they are up to higher doses than when they are only up to lower doses.  They also said that if a person is going to have a reaction of any significance it tends to happen when they are on their way to 1 peanut.  Once you get to 1 they say it is easy to get to 2 and then once there, easy to get to 3, and so on. 

[lakeswimr]

I agree that for new people it is good for them to know to read about this topic before deciding but it is also good to know that NE FA are going forward with treating people and claiming high success.  One reason I didn't even look into them sooner was because of things I was reading here.  I was shocked when I heard them claim a 95% success rate.  That's not the impression I got from reading things here.  I think that is important for people to know.

Eventually odds are my child would end up accidentally eating peanuts.  I would rather he do this program first.  If it doesn't end up working we will have to avoid peanuts which we are already doing.  If he starts having significant stomach issues during this I will have to think carefully about EOE.  So far he has had zero symptoms.  It amazes me.  If all we get out of it is that he doesn't have to worry about contact ingestion for peanut that alone would be huge for us.

[CMdeux]

  All of that makes complete sense-- and the ONLY thing that doesn't make sense to me (or to our allergist, who, recall, used to be affiliated with some of the same physicians who are now doing desensitization clinically) is the claims of success rates topping 90%.     

The reason that doesn't quite add up for us is that this is just SO far from what controlled OIT studies have found, which is more along the lines of 60-70%.  The other bit that doesn't make sense is the part about serious reactions in just 1-2% of individuals.  Clinical studies have demonstrated that rate to be somewhere between 5-10% of patients, depending upon the allergen.    It's a big difference.  Maybe it's selection bias, maybe it's less rigorous intake protocols, maybe it's a lot of the little details in refinement (noted by Lakeswimr)-- but in any event, I have to wonder how much of that stuff is coincidence or luck rather than actual causation (that is, why carbs and not something else-- and why "before" as well as after dosing... and why would illness not play a role when it seems to have done so in the controlled studies...).  Less than 500 persons is still pretty small numbers when you think about how different the manifestations of atopy can be from one individual to another-- and honestly, without a negative control group (actually, SEVERAL control groups), numbers up to a thousand or two aren't even completely compelling.  Yet.  I also wonder if they simply don't know the reasons when people drop out of treatment and don't say why they've done so.  That was one factor in the high success rates of very early OIT trials, like the one that Melissa's DS participated in at Hopkins.  When participants dropped out of the experimental arm of the protocol, they weren't followed super-aggressively to determine WHY. 

That's not to say that it doesn't work precisely as stated for some, maybe even "most" patients who do it. 

One hesitation that our allergist in particular has had w/r/t DD doing something like this is that her immune system seems to be generally rather trigger-happy.  That is, we KNOW that pushing on one thing with immunotherapy is likely to result in unpredictable, unrelated, but definitely IgE-mediated stuff popping up elsewhere.  So for people like her, it can be a game of Let's Make a Deal-- I just want to know what IS behind all of those doors, myself.  If one of them is something worse, then I'd like to know what those odds are, and whether or not they could be higher/enhanced for a particular individual, and how would one know that at the outset of treatment.

[lakeswimr]

I think that they sound like the actively discourage people from doing it if they have had very, very severe past reactions.  They also do tell people not to take the daily dose if one is ill or has a fever.  Also, if people miss more than 1-2 doses you have to call them and see if you need to come in again before taking your dose or if you need the dose backed down.  There are probably a few other 'refinements' that I didn't remember as well.

As for why carbs before and after, they find that it slows down the rate of absorption of protein.  Ditto not exercising and not taking hot baths/shows.  They find that things that raise the metabolic rate increase the absorption rate.  So, while a person's body might be able to handle x amount of peanut at y rate, increasing that rate could make the person react because they can't handle the speed with which the protein is getting into the blood stream.

The initial studies--did they have the same protocols and precautions that I am mentioning here?  If not, then it isn't apples to apples but some other comparison.  They used to have a higher % react but once they realized the things that tended to be linked to people having sudden reactions to previously tolerated doses they found a very small % react. 

I think eliminating people who are on the most sensitive end of things, going super, super slowly with those who are most sensitive of those they do treat, having people take the above precautions, etc must have greatly decreased the % who have serious reactions. 

There are other things, too--we have to be careful not to let the peanut get heated.  So, even when driving home in the car I had it in the A/C with us rather than in the trunk.  I put it in a cool part of our house to store it.  If people who did this in the past did not take care with this, they could have less potent doses and then get a new set of doses and not be ready for the dose increase.

Another reason I didn't do this program earlier is that I have a friend who did it when they first started.  Her child is one who reacted a lot and had to have the epi several times.  He was one who would take his dose and go exercise or take a hot shower and then react.  He also was one who sometimes didn't eat first and would react.  She told me that they could not get him to one peanut and keep him there reliably and eventually they dropped out.  I talked to her more recently and she never told me until then that they had gone back and gotten him up to 3 peanuts a day.  She stopped doing it because it was a pain to do peanuts each night but otherwise, it worked for her child.  Her stories of his reactions (he was one of the very first patients 2-3 years ago now) were a huge reason for me not doing it.  But now I know that his reactions stopped when he started doing the no exercise, no baths/showers after, carbs before and after, etc.

[CMdeux]

That is really great detail, Lakeswimr!  Thank you so much for posting that. 

It all makes complete sense-- well, that is, I can understand why the exercise thing ties in, though it's not precisely raising the rate of metabolizing the protein so much as tweaking the immune response and circulatory system, just like with SCIT (allergy shots)-- seems like fats would slow protein absorption more, but   who knows.  Having eaten something definitely seems wise, anyway.  Being careful to keep the doses at controlled temps also makes complete sense to me. 

I do know of at least two people who truly tried to do all of that "right" but wound up dropping out because of frequent or severe reactions, and of course there are the EoE stories (nobody wants to think about those, for sure, even if you're doing some kind of home-brewed version of this with baked milk or egg).

It definitely seems like it gets more kids to "tolerance" than doing nothing, anyway-- though again, things are changing so fast with the cohort of kids born after 1996 that who knows, really, what percentage of them are going to be "natural outgrowers" in the end.  Maybe most of them-- which might mean that this isn't really budging the natural history of the disease.  Hard to say.  It might be that the cohort that is not really in a position to try OIT is the portion of the cohort that won't outgrow on their own... and that THOSE numbers may well have not shifted much since 1980, and stayed relatively constant.  At least as a paper napkin calculation done in my head, those numbers more or less add up for me.  Kids are just outgrowing food allergies later than they used to, apparently.  It's not yet clear that there are actually MORE food allergic people in young adulthood.  We'll know in about five years, I guess. 

Anyway.  Things that I have talked about with the allergist re: our egg desensitization.  It's been life-changing, for sure.   I'm really glad that some of our members here have had such lovely experiences with OIT and peanut.  The others that I know have done this are Hedgehog and Aggiedog (though not with the same docs)-- both with stellar results.   

[lakeswimr]

DS's former allergist (now retired) at first advised we do desensitization before they started offering it.  Then he had a milk-allergic child have a bad reaction and advised against it and felt it wasn't ready for prime time/didn't have the kinks worked out.  We got a new allergist this year and he strongly recommends it.  He said, "what else is there?"  He said, "it's your best bet right now." 

There is someone at KWFA who did desensitization for milk and egg starting with baked at home working with Dr. Wood's guidance and now instead of having a sig line that reads milk, eggs, peanuts, tree nuts, her sig line reads just peanuts and tree nuts.  That makes me wish I had pushed the baked stuff faster/harder.  She pushed through stomach issues, not having heard the tie to EOE, and her son is perfectly find.  Milk was the most serious FA for that child and now he can all forms of it. 

I don't know what is right.

I would have guessed that fewer our outgrowing and more have FAs.  Kids are outgrowing later, that's for sure.  I wonder why.  Maybe because better labeling allows for more complete avoidance and total avoidance helps avoid reactions but also can make the allergy get stronger.  maybe minor xcontam in the past helped kids outgrow.