The First Big SLIT Trial Just Ended...

...and the results are...interesting.

For those of you who are not obsessed with the current smorgasbord of clinical trials underway, SLIT stands for sub-lingual immunotherapy. The therapy has been used successfully in Europe for many years to treat environmental allergies. It's been used more sporadically and with less certain results to treat food allergies. I know of at least one clinic in the United States that has been administering SLIT for several decades.

The question has been...does it really work? Other trials have shown mixed results. (I wrote an article on this back in July if you're really interested.) This most recent study was a more comprehensive approach involving 40 kids, sponsored by the National Institute of Health and held at several locations.

Kids who participated were given either placebo or drops containing peanut protein. About a third of the kids in the peanut drop group experienced an itchy mouth or throat, but only a few had symptoms more severe than that. (However, one subject did have an anaphylaxic event after a dose at home and ended up dropping out of the study.) At the end of the 44 weeks, the kids who suffered through dose after dose of saline for nothing got to choose whether to participate in an accelerated higher-dose SLIT experiment over the next 24 weeks. Kids in the first peanut group just continued with their slower build-up.

The kids varied a lot with regard to how much peanut they could tolerate at the outset. For some kids, the first symptom occurred at just 6 mg. Keep in mind that a peanut is about 300 mg, so this means these kids could detect 1/50th of a peanut. However, the actual dose they consumed before having a objectively-confirmable reaction was as high as 196 mg, or 2/3^rds of a peanut.

So what was interesting about it?

It worked...kind of. Of the kids in the original peanut group, 14 out of 20 were able to consume 10x the amount of peanut after SLIT as they did before. The problem was that many of these kids did not get up to a very high dose at the start, so 10x the amount of peanut was still not very much peanut. The median dose they achieved at the midpoint of the study was 496 mg (about 1 2/3 peanuts). At the end of the 68 weeks, the median was 996 mg, or just over three peanuts. This is definitely some significant wiggle room with regard to cross-contamination, but it's clearly not full desensitization, at least for most kids.

The kids who got the shorter course of peanut drops after placebo did almost as well. There were seven "responders" out of 16 in this group (some people dropped out along the way for various reasons, including fear of more challenges and even pregnancy!). The median amount they could eat after just 20 weeks of SLIT was that magical 496 mg number.

The amount of time SLIT was given did make a difference in a few cases. The study goal for desensitization was 5 whole GRAMS of peanut (5000 mg). During the 44-week challenge, no one made it to full desensitization. However, after 68 weeks, three of the kids were able to consume 5 grams (16 peanuts), and one ate 10 grams (32 peanuts).



Peanut-specific IgE levels didn't go down. The kids who got the peanut saw their IgE levels go up at the beginning of the dosing, then back down toward the end. However, in the end, the level of IgE ended up at about the same point as when they started and wasn't any different from the placebo group.

However, there was a noticeable difference in IgG4 levels: in the peanut kids, they went up much more than with the placebo group. Just as with good and bad cholesterol, it may be that a change in the "good" number (IgG4) is a more important marker of tolerance than the "bad" (IgE) number. Skin tests also changed significantly for the peanut kids. Bottom line is that IgE doesn't really seem to be telling us much with regard to development of tolerance.

Spontaneous tolerance DOES occur. Here was the weirdest part of the study for me: two kids in the placebo group  were actually able to pass the 16-peanut challenge at the end without any real therapy. Keep in mind that these were kids who had already failed a challenge just a few months before (one got just hives and itching; the other got hives, plus felt sick).

The study authors just kind of shrugged about this one and said "hey, we really don't know how this all works and maybe even older kids, or kids whose IgE isn't all that low, can spontaneously develop tolerance." One of the kids saw a decrease in IgE/increase in IgG4; the other saw an increase in IgE and a decrease in IgG4. No help there!

So what changed? Maybe the time in the year the kids were tested made a difference. They were both teen boys, so maybe testosterone kicked in and suppressed inflammation. Whatever the reason, both kids are now openly eating peanut.

So...if you're anything like me, you found the information about SLIT interesting and the information about the kids who got placebo and passed anyway INTERESTING! You can tell when you read the study that those kids really mucked up the nice, neat results. Sometimes, though, it's the thing that you're not looking for that ends up being the most important part of a research study.

If you'd like to read the whole complicated study for yourself, you'll find it here.


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