Desensitization Programs in the US -- OIT SLIT SCIT

[Arkadia]

None of this is advice, just what is supposedly common public knowledge. When I first became aware of Tannox and Xolair, the first thing I thought of was Enbrel, having come across several instances where the cancers they speak of, some widespread, were an issue.  Apparently they are similar in some fashion, similar enough to be compared as "Antibody Market Share Leaders". How similar they are, maybe CM could shed some light on? It would be appreciated.

http://tinyurl.com/8284hdc

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http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/UCM070725

FDA is investigating approximately 30 reports of cancer in children and young adults.  These reports were submitted to FDA's Adverse Event Reporting System over a ten-year interval, beginning in 1998 after approval of the first TNF blocker, and extending through April 29, 2008. These reports described cancer occurring in children and young adults who began taking TNF blockers (along with other immuno-suppressive medicines such as methotrexate, azathioprine or 6-mercaptopurine), when they were ages 18 or less, to treat Juvenile Idiopathic Arthritis (JIA), Crohn's disease or other diseases. Approximately half the cancers were lymphomas and included both Hodgkin's and non-Hodgkin's lymphoma.  Lymphoma is a cancer of the cells in the immune system.  Lymphoma is not a recognized complication of JIA or of Crohn's disease.  Other cancers reported included leukemia, melanoma, and solid organ cancers.  While cancers are known to occur in children and young adults, the reports of these events in children and young adults receiving TNF blockers are of concern and deserve further investigation. Long-term studies are necessary to provide definitive answers about whether TNF blockers increase the occurrence of cancers in children because cancers may take a long time to develop and may not be detected in short-term studies.

[ajasfolks2]

(Just quietly reading along here.  Very interesting and informative discussion -- thank you all!!)

Carry on!   

[rebekahc]

I agree, part of DS's improvement today may have happened anyway. However, he went from needing 24 puffs of albuterol a day just to barely come out of the red zone, multiple hospitalizations for status asthmaticus with 3-4 days of oxygen each, prednisone, beyond max doses of maintenance meds, etc. to NO asthma and NO allergies within a three month period long before he hit adolescence. The only explanation is Xolair.  So, even if he would have "outgrown" his atopy, he would have suffered for years without the Xolair.  Totally worth it.

if my son outgrew earlier than two years ago, i dont know---he was on singulair and allegra without question until the new ped stopped them.

It sounds as if the singulair and allegra kept your DS's asthma well under control. 

yet major metropolitan children's hospital petitioned us to be part of the Xolair study. Why do  you think that was? Was it cherry picking?

If he had been part of the non-placebo group, would you say results related to him might have boosted confidence in the drug?

Or...could it possibly have been the delicious fringe of having a peanut allergy/multiple food allergy, for which the study was not approved?

Neither?

Just sheer ignorance?

My guess?  Because he was relatively stable he qualified for the study.  He was bad enough, but not too bad. 

Perhaps they offered all their patients the opportunity?  We, too, live in an extremely large metropolitan area and are treated at a major children's hospital.  When one of our various specialists is involved in a study involving one of our dx'es, we've always been offered the chance to participate.  I always assumed everyone was.  Many of the studies, we just had to answer questions and the doctor tracked data, so we would often participate.  The one study I allowed DS to actively participate in was a Singulair vs. Flovent study.  They gave us a palm pilot (this was before the age of smart phones) and we had to track his peak flows several times a day and then download the data once a week or so.  FWIW, neither med did much for DS, but Flovent was slightly better.  According to our pulmo, Singulair only works for about 30% of patients.  For those for whom it works, it's great - everyone else might as well have a placebo.

I think it's important to remember the distinction between a study (research) and a trial.  In the studies, they are basically comparing data WRT a pretty broad population where in a trial they're actually testing the effectiveness/safety/etc. of a particular med for a specific diagnosis.  A trial will have much more stringent enrollment criteria than a study.  In the Xolair study you mention, I'm surprised once you chose not to use the med that they didn't ask you to allow them to track data on your DS as a non-Xolair using asthmatic. 

[Arkadia]

I agree, part of DS's improvement today may have happened anyway. However, he went from needing 24 puffs of albuterol a day just to barely come out of the red zone, multiple hospitalizations for status asthmaticus with 3-4 days of oxygen each, prednisone, beyond max doses of maintenance meds, etc. to NO asthma and NO allergies within a three month period long before he hit adolescence. The only explanation is Xolair.  So, even if he would have "outgrown" his atopy, he would have suffered for years without the Xolair.  Totally worth it.

if my son outgrew earlier than two years ago, i dont know---he was on singulair and allegra without question until the new ped stopped them.

It sounds as if the singulair and allegra kept your DS's asthma well under control. 

yet major metropolitan children's hospital petitioned us to be part of the Xolair study. Why do  you think that was? Was it cherry picking?

If he had been part of the non-placebo group, would you say results related to him might have boosted confidence in the drug?

Or...could it possibly have been the delicious fringe of having a peanut allergy/multiple food allergy, for which the study was not approved?

Neither?

Just sheer ignorance?

My guess?  Because he was relatively stable he qualified for the study.  He was bad enough, but not too bad. 

Perhaps they offered all their patients the opportunity?  We, too, live in an extremely large metropolitan area and are treated at a major children's hospital.  When one of our various specialists is involved in a study involving one of our dx'es, we've always been offered the chance to participate.  I always assumed everyone was.  Many of the studies, we just had to answer questions and the doctor tracked data, so we would often participate.  The one study I allowed DS to actively participate in was a Singulair vs. Flovent study.  They gave us a palm pilot (this was before the age of smart phones) and we had to track his peak flows several times a day and then download the data once a week or so.  FWIW, neither med did much for DS, but Flovent was slightly better.  According to our pulmo, Singulair only works for about 30% of patients.  For those for whom it works, it's great - everyone else might as well have a placebo.

I think it's important to remember the distinction between a study (research) and a trial.  In the studies, they are basically comparing data WRT a pretty broad population where in a trial they're actually testing the effectiveness/safety/etc. of a particular med for a specific diagnosis.  A trial will have much more stringent enrollment criteria than a study.  In the Xolair study you mention, I'm surprised once you chose not to use the med that they didn't ask you to allow them to track data on your DS as a non-Xolair using asthmatic.

They probably did. At that point, I high tailed it out of there. trial or research, risk must NEVER outweigh the benefit, and the risks associated with the injectible medication far outweighed any potential benefit for him.

Also....in either case, making someone part of such an endevor cannot involve them having to quit taking a medication or participating in a regime that would put them at an increased risk.


Designing them does take some forethought and often, researchers find their hands tied, and yes, unethical breeches DO happen. Just look at Wakefield....

Xolair was nothing unique and not the first horse in this race. There were known plausible outcomes in that drug class. Things you weigh heavily before inducting persons in and putting them at risk.

[Arkadia]

FDA and Xolair:

http://www.reuters.com/article/2009/11/18/fda-xolair-idUSN1812824820091118

Dr. Peter Starke of the FDA's pulmonary and allergy products division told the meeting that while the drug had met its targets in clinical trials, its effectiveness in children was "invariably small and clinically modest."

The drug's current label for adult use contains a warning that it may cause anaphylaxis -- a severe allergic reaction that can be fatal -- and could also put patients at risk of cancer.

In no way was my son a candidate to participate. Non food allergy related, not one prior hospitalization, not even a visit to the ER related to Asthma.

[CMdeux]

Well, TNF blockade is a completely different drug class than the IgE antibody drugs like Tanox/Xolair:

http://www.nature.com/jidsp/journal/v12/n1/full/5650029a.html

Different mechanism, I mean.

What I find most appalling-- but highly instructive-- about the story of Embrel is that the drug was brought to market almost entirely EMPIRICALLY.

This is exactly the same kind of design paradigm which is being followed for atopic disorders (including the clinical work into desensitization and suppression of anaphylaxis) via drugs, desensitization protocols, and herbal treatments.  Nobody KNOWS why some of it works... just THAT it seems to.

Personally, that's something that makes me very very wary.  Because it often comes with a pricetag that you can't see when you sign on-- a pricetag that NOBODY knows at the time, more to the point.  Nobody knows enough about the underlying mechanism of how severe atopy happens to start with-- so treatments are tinkering with an engine using a timing light, basically, without knowing what makes the pistons move, or that without lubrication, the entire thing will eventually just seize.  (This isn't a perfect analogy, but it's as good as I've got today)

The herbal treatment is the one that looks the most promising (overall) at this point-- but the problem is that nobody has any idea what the mechanism is.  Just like with Embrel when it was first marketed.  It worked-- and it seemed to be unlike anything ELSE, mechanistically (which can be tested without knowing HOW it is different, by the way).    It worked when nothing else would.

Nobody stopped to consider that maybe the "Yeah, but HOW does it work?" might be important down the line in terms of side-effects.  Because it never occurred to anyone on the clinical side that it might matter (much).  Clinicians aren't (generally) people that have a good grasp on the underlying biochemistry here.  Not that they should, mind you-- they are physicians, not scientists.  But the problem is that there is so much pressure to do SOMETHING for patients that there are probably a lot of areas where the clinical trials and treatment protocols are running out ahead of the basic understanding of the system.   

I so wish that treatment design were being driven by better basic science.  <sigh>  At least with straight up immunotherapy, there is a considerable amount of empirical history so support the understanding of HOW it works. 

I also don't judge anyone for wanting to participate-- even if the risks are largely unknown right now-- because I am extremely sympathetic to how hard MFA/LTFA can be, in terms of quality of life.  I'm in that boat with y'all, and I know (bitterly) how high the cost is to a family to live with merely having 'avoidance' as your toolkit.  We're living it, too. 

Autoimmune disorders are some scary, scary stuff, though-- and that is one grab bag that most people should think twice about reaching for.  Knowing how to turn things ON in that system (via external pressors) isn't the same thing as knowing how to shut them back off again.  Researchers know how to produce an anaphylaxis model in mice.  What they do NOT know is how to "undo" that transformation.  The same thing is true in a variety of other autoimmune disorders, from RA to MS to TypeI diabetes. Heck, cancer is ALWAYS on the table when you tinker with things.
  Start turning knobs in that system in the hopes that {improvement in autoimmune disorder} will happen...  and you never know what you might end up with alongside that improvement.  That would be okay if we understood completely how to UNDO changes that we do, or if it were clearer what down-stream effects each change would make.  But that isn't where the science is right now.  KWIM?   So the benefit to an individual would have to be VERY large to justify the risks-- at least right now.  For some people, that is almost certainly true.  (R's son clearly benefitted a great deal from his Xolair treatment, and I know one other person who has, as well.)  But for someone like Ark's DS1, yeah-- I wouldn't have signed on for it, either. 

We refused Embrel for DD's eczema, too.  Unknown mechanism meant that for her eczema, no way was the *unknown* risk worth the benefit.     

[Arkadia]

Well, TNF blockade is a completely different drug class than the IgE antibody drugs like Tanox/Xolair:

http://www.nature.com/jidsp/journal/v12/n1/full/5650029a.html

Different mechanism, I mean.

actually, I do understand that much. (contrary to what you might think about healthcare providers  ) We're not all, if hardly the philistines you imagine.  Quite well read, and do think on a cellular/molecular level quite often regarding processes, and a wealth of information at our fingertips, eagerly devouring downloads of information on our patients and rubbing noggins with some of the best.  We understand molecular biology to some degree, or are capable of it, given the chance.  Full disclosure:  My end of medicine demands it, and I work in a rabid teaching institution where there's not much we won't attempt if we can find a shred of evidence----wait, yes....Enbrel. You were saying?

I guess what I wasn't getting into my thick noggin that, what you said, a lot of it is unknown. I tend to NOT assume a lot of these projects are um.....U.F.O.'s., even though many participants in research forget they are involved in something, uh---experimental. And yes, what you said about being in this together. No fingers pointing at anyone, merely pointing something out, and that it's not a perfect science, like say....math.

There's wiggle room. 

That that is an acceptable standard starting out, provided there is some redeeming, immediate, even if only ephemeral, value found.



I think people feel more comfortable with unknowns than almost infintessmal risk factors when presented with a choice. That they fail to understand a 20 percent sucess rate means 80 percent dissatisfaction with possible serious consequence. That means L.U.C.K might play a role, and humans are by nature, gambling beasts.   

Or maybe not. I guess what was nagging me was if those possibilities of defeat and or serious adverse effect were something that could be influenced or within our control. It never occurs to me that things haven't been thoroughly vetted.....at first, naive creature I be.

Aside from you know, obvious risk factors, or contraindications. (and I've seen OODLES of medications used in the presence of BOTH. Off label, even.

What I find most appalling-- but highly instructive-- about the story of Embrel is that the drug was brought to market almost entirely EMPIRICALLY.

welcome to the practice.

[Arkadia]

i mean, how many lab scientists know this? (discussing it just last night, having a good chuckle, mythology and all):

http://www.cjem-online.ca/v6/n1/p48

In a 1967 prospective study, Taylor and Weil tested the effectiveness of the Trendelenburg position in 6 hypotensive patients in clinical shock and 5 normotensive controls.3 In 9 of the 11 of patients, Trendelenburg positioning was ineffective, causing reductions in systolic, diastolic and mean arterial pressures. These authors noted that, in the head-down position, the viscera weigh down the diaphragm and compromise lung volumes. They also suggested that patients were at higher risk of cerebral edema, retinal detachment and brachial nerve paralysis.3

it's pretty old news, but propaganda to the contrary abounds. There's something to be said about a practice, and in-the-field experience.

[Arkadia]

FDA and Xolair:

http://www.reuters.com/article/2009/11/18/fda-xolair-idUSN1812824820091118

Dr. Peter Starke of the FDA's pulmonary and allergy products division told the meeting that while the drug had met its targets in clinical trials, its effectiveness in children was "invariably small and clinically modest."

The drug's current label for adult use contains a warning that it may cause anaphylaxis -- a severe allergic reaction that can be fatal -- and could also put patients at risk of cancer.

In no way was my son a candidate to participate. Non food allergy related, not one prior hospitalization, not even a visit to the ER related to Asthma.

full disclosure:  There's a good number of things I *don't* go to the E.R. for, that aren't E.R. worthy, that the vast majority of laypeople will head for the registration desk for. I know a good number of HMO's won't pay for an ER visit unless you are admitted, and so do health care providers. That's not saying anything about motive, but just fact. That said, I don't have an HMO, never have, and I can count on one hand the number of times my children have been to the ER (4), and three resulted in admissions. 9-10 day stays. Fourth trip to the ER was a foreign body (metal) in my son's eye. I knew it had to go, and after several hours of flushing, it hadn't budged. Turns out it was embedded in the sclera. Holiday weekend too. Ah, hell has many levels.

[Arkadia]

I remember plenty of Xopenex nights....with several children.

[Arkadia]

I remembered something today as I was contemplating whether or not to use the "Protopic" ointment prescribed for my daughter tonight by a pediatric dermatologis from the children's hospital. Insert from the pharmacy said something about: "longterm effects are unknown" and something about skin cancer and tumors. Not your typical "steroid" creme, actually it's not a "steroid" ointment at all. It's active ingredient (tacrolimus) is a drug typically used to suppress the immune system for organ transplants.

And she's not even fully vaccinated.

I used it once on her face (a half a pea size amount) and the results....improvement overnight. She's getting scaly and dusty however, now 24 hours without an application. If I use it on every area of eczema....it's going to be a very significant amount, and I worry about systemic effects, considering the broken nature of her skin.

She has oodles of dusty white scales around her eyes, eyelids, mouth, nose, jawline. She looks like a ghost. Petroleum jelly just makes it angry and red. Vanicreme is useless on it.
http://www.drugs.com/pro/protopic.html

[aggiedog]

Because it often comes with a pricetag that you can't see when you sign on-- a pricetag that NOBODY knows at the time, more to the point. 

My sister has been on Embrel and Remicaid, which I'm guessing is similar in action.  For her, it was life changing.  When your life is that miserable, a chance of the devil you don't know is better than the devil you're already living with.

I totally understand your point.  Just saying sometimes consenting adults are willing to chance it.

Ark, I LOVE the tacrolimus type meds.  For bad eczema around the eyes, there is nothing better.  Steroids work great, right up until you are blind from your uncontrolled glaucoma and cataracts.  I warn all my patients about the possible risk, and they all prefer to use it anyways.  Agreed, slathering all over a small child's body is a much larger dose than an adult's eyes, but for them it makes the risk more acceptable I think.

[Arkadia]

Ark, I LOVE the tacrolimus type meds.  For bad eczema around the eyes, there is nothing better.  Steroids work great, right up until you are blind from your uncontrolled glaucoma and cataracts.  I warn all my patients about the possible risk, and they all prefer to use it anyways.  Agreed, slathering all over a small child's body is a much larger dose than an adult's eyes, but for them it makes the risk more acceptable I think.

The derm only wanted me to use the protopic on her face, mometesone on the rest of her body. (the visit was um...about 45 seconds tops, dh had to give a history to possibly three "students" before she came in and a pa handled the rest.  She spent a lot of time the first visit, but this is why I LOATHE major networks with brand names that are teaching institutions. We wait FOREVER so we can see the person with all the letters after their name. Not some newbie greenhorn.

I should have taken her and made the PHYSICIAN do a thorough assessment. They didn't even notice her swollen/infected and now near grotesquely swollen pinky finger because they did a sh***y ASSESSMENT. Actually, hubby said they rushed out, and he was so pissed, when the doc left after less than a minute he didn't bother bitching.  It has several deep cracks in it, and no, dear doc in the box, the medicine isn't working.  We've already been the mometesone route, (and was on triaminolone ointment).

I mean, do these people understand why even professionals like myself don't trust them? Or what they prescribe? It's a mill. I got better service (and more effective treatment) from my pediatrician regarding it. It's just I can't put the lotion he prescribed by her eyes (it OTC Eucerin with intensive repair and has alpha hydroxy in it--instructions say to avoid eye area)

Several days after an appointment with a children's specialist you wait 2-3 months to see shouldn't leave you at square one again and items missed.

I feel like they just juggle a list of meds, and throw in a big gun once in a while, hoping to keep you at bay until it resolves or becomes fulminant. I swear, it's eczema, not the plague, and they are the top of the food chain.  I'm so dissapointed. My daughter is dissalusioned to. Big fancy office, play area, televisions, doll houses and doctor can't make the itch or the red angry plaques go away. (but hey, great marketing)

If she only new her odd belly ache might be from the new medicine. a****oles.

If they put some thought into the medicine (and a decent exam/followup) I'd have more faith in them and be less po'd. When will professionals learn a little time and thought go a long way?

[SouptoNuts]

But back to desensitization...this has been very helpful.  Thanks!

[LinksEtc]

"Oral Immunotherapy for Food Allergy: Not Ready for Prime Time"
http://www.asthmaallergieschildren.com/2012/05/11/oral-immunotherapy-for-food-allergy-not-ready-for-prime-time/

I wish to caution that widespread adoption of any OIT methods is premature, and may lead to crushing the hopes of patients, and worse.