Thread by @ATLergist

‼️ATTENTION: If you care about #PeanutAllergy or know someone who does, please 👀 this 🧵‼️

An extremely important study was published over the weekend... (1/N)

thelancet.com/journals/lance…

We already have good evidence that oral immunotherapy (OIT) is a treatment that can change the immune response to peanut and result in clinical desensitization, as measured by the provocative dose in a post-treatment oral food challenge. (2/N)

As a result we now have an FDA and EMA approved peanut OIT product for use in selected patients aged 4-17 years, and some allergists use other sources of peanut protein in their own "unapproved" OIT regimens.

This can be life-changing therapy, but...(3/N)

...it has limitations, the main one being that its effects are transient; the desensitization wears off when the treatment is stopped. And there are some (largely manageable) safety issues, as there are with any form of immunotherapy. (4/N)

So the search has been on for awhile for a way to treat peanut allergy that leads to a more permanent result, one we would call "remission" of the condition.

Several years ago, the focus of these efforts turned to early intervention treatment in young kids...(5/N)

...since peanut allergy usually presents in the 1st or 2nd year of life, & IgE levels often are lowest at the time of this initial reaction. Like many other childhood conditions, allergies may be most effectively treated early due to some "plasticity" in immune response (6/N)

...and in fact some early proof of concept studies seemed to suggest this was the case.

Including mine, called the DEVIL study, which was funded by my first @NIAIDFunding K23 grant. And the N=49 data did look nice. Nice enough for some Canadian allergists...(7/N)

...to begin a real world study of early OIT for peanut allergy, which looked promising & largely replicated DEVIL.

So - a good start, but single-center, small, and/or uncontrolled studies often overestimate effects, or even lead us the wrong direction (8/N)

So when I used to go around presenting the DEVIL data, I would often get asked about how to implement this kind of treatment because people were so convinced it was the right thing to do. My response was usually to thank them for their confidence in our data...(9/N)

...but to point out that large, placebo-controlled studies are the kinds of studies on which we should ideally base big changes in practice, like for example using immunotherapy in young kids.

Well, that study has now been published...(10/N)

...and it provides IMO *definitive* evidence that peanut allergy should be treated early in life:

after ~2.5 y of OIT, 71% in active group vs. 2% in placebo group were desensitized

AND

21% vs. 2% tolerated ~ 16 peanuts with no reaction 6 mo after stopping treatment (11/N)

(PLUS those 21 also ate 8 gm of peanut in 1 sitting AFTER successful completion of that challenge to ensure they were in remission and fully ready to consume peanut)

AND... (12/N)

...taking a slightly more modest view, 57% of active vs. 4% placebo could tolerate between 1755-3755 mg of peanut protein 6 months after stopping OIT.

This is a huge result! That kind of protection is clinically meaningful *six months* after no treatment (13/N)

What's more, there is good reason to think that these are "worst case" data compared to real world use. Why?

1. The kids were older in this study - median 39.3 months at entry, tho it was open to kids 1-4y

2. Their median peanut IgE was already 53.1 (14/N)

We suspected based on multiple previous studies that kids do better when younger and/or have lower IgE levels.

And IMPACT basically proved it. Although this is from a post-hoc analysis, I consider this the money shot from the whole study: (15/N)

Shown here is the predicted probability of REMISSION by age and baseline IgE level. Blue is favorable.

This is a spectacular result that should change allergy practice everywhere. It will now change my practice. Young kids with low IgE levels do extremely well (16/N)

Can't talk about benefits without talking about harms, so yes there were systemic reactions to doses and EoE and withdrawals - but no worse than previous studies in older kids, which is important considering many were fearful of enhanced risk to preverbal children (17/N)

Very interesting changes also seen in the immune systems of these children that convince me that the effects seen were therapeutic in nature, and not due to the spontaneous improvement that does occur in ~ 20% of young kids with peanut allergy (18/N)

Bottom line: This is a landmark study that should bend the curve of this disease's trajectory. The study teams, @NIAIDNews & Immune Tolerance Network are to be congratulated. It was a privilege to be a part of it. (19/N)

Most importantly - huge thanks to the children & their caregivers for their brave participation. Clinical research is not easy, but as the study foreshadowed, your sacrifices will have lasting "impact" on countless others (end)