FARE’s Chief Medical Advisor on Why Standardizing OIT is Needed Now

in Food Allergy, Managing Allergies
Published: May 13, 2019

Dr. Thomas Casale
The non-profit Food Allergy Research & Education (FARE) announced on May 1, 2019 that it plans to organize a summit to discuss food allergy oral immunotherapy (OIT) to consider the risks and benefits of the therapy, knowledge gaps that still surround it, and developing standardized approaches to the practice.

The announcement of the Food OIT in Practice Summit, scheduled to take place in Houston in November 2019, followed the annual FARE Research Retreat.

To gain an understanding of the type of consensus FARE is looking to build among allergists, government agencies and the public, Allergic Living Editor Gwen Smith recently had the following conversation with allergist Dr. Thomas Casale, FARE’s Chief Medical Officer for Operations.

He expands on why FARE sees the need to develop some standardization of OIT protocols, in a time when an increasing number of allergy clinics are already offering oral immunotherapy to food allergy patients.

Allergic Living Speaks to FARE’s Dr. Thomas Casale

What is FARE hoping to achieve and who are you hoping to have involved in the discussion about OIT?

Dr. Thomas Casale: The biggest thing that FARE wants to address is that there are over 30 million patients the United States with food allergies and a number of them are already seeking some sort of therapy. What has become increasingly evident is the potential for them to get oral immunotherapy to one or more allergenic foods in private practice.

We predict that, within a year, the FDA will approve Aimmune Therapeutic’s [peanut OIT] product, which will give us a standardized product for peanut. But patients are often allergic to many different things.

What FARE would like to do is to get individuals in a room to discuss the use of oral immunotherapy for food in practice, as it exists now. The idea would be to determine whether or not we could come up with some consensus recommendations on how to make treatment safer and more effective for the patients that are already undergoing oral immunotherapy.

In the best of all worlds, I would like have the AAAAI and the ACAAI involved. I would like to have the FDA involved, the National Institutes of Health, some of the CoFAR [Consortium of Food Allergy Research] investigators, some of the FARE medical advisors, and some of the people that in practice have been doing OIT. I’d like to have patient representatives too, because their voices should be heard. I think it’s important that all of them are represented.

Is FARE advocating using OIT at this time?

TC: No. I want make it clear that at FARE, we are not advocating the use of OIT, but rather just trying to protect the patients who are looking at this therapy as a potential option. We’d like to get in a room along with regulators and researchers and see if at least there can be some guidance on – if an allergist is going to do it, how best to do it.

Whatever comes out of this discussion would not be a guideline, because we don’t have any data for that. It would be more a consensus opinion piece, which I think could be helpful to guide practice.

The fact is that the number of individuals being treated with OIT is increasing, it is already being used in a number of private practices. Whether or not there is regulation, that train is moving, and it’s not going to be stopped.

Studies with peanut and egg have shown that OIT will successfully desensitize a majority of patients. But the therapy hasn’t been successful in everyone and reactions are reported in a minority. Yet a few clinics are making claims of success rates of up to 90 or even 100 percent, which seem extraordinary, and doesn’t appear science-based. Given that, if a family contemplates pursuing OIT, what should they look for when considering practices?

TC: I would say, first, you would probably look for someone that has some experience with OIT, and second, someone who can give you a good estimate of the risk-benefit of the treatment.

And third, to make sure that the ability to treat acute allergic reactions or adverse events from the OIT is there – not only in clinic but around the clock. It has been the experience of a number of centers that did the Aimmune studies, for example, that acute allergic events don’t necessarily occur while patients are in clinic. They could occur any time. So there has to be a big support system involved.

Getting people in room talk about these issues, might allow us to say, “If you’re going to do this in practice, let’s try, Number 1, to get some products that we could agree on that would reasonable to use while we’re awaiting FDA approval of these products [Editor’s note: A reference to Aimmune’s AR101 protocol and DBV Technologies’ Viaskin Peanut patch].

We also need to determine some sort of treatment effects that everybody could agree on, and how to assess that. Because what we’re getting from the OIT practices are a lot of retrospective analyses. They’ll say: ‘We treated 100 patients and 70 did really well.’ And they look back at the patients’ records and see how many people did better, and they report that.

The best science, however, is done from a prospective standpoint, where you say: ‘I’m going to treat 100 patients and I’m going to follow them for these parameters, and determine whether they get better. There’s a big difference, and gathering prospective data from practices, I think would very important for us to assess the true efficacy and safety of this [OIT] in private practice.”

What about the person whose child’s allergy isn’t peanut or egg? For instance, some small milk OIT studies have found a greater variance in improvement with that allergen and more reactions in the escalation phase. Or perhaps sesame, which can be a particularly potent allergen. For the person with a child who has one of these allergies, how do they know whether it’s safe to undertake OIT?

TC: This is why I think it’s very important to talk about these different issues than to try and come up with a consensus document. If you take any one of these allergens where we don’t have a standardized product, the concern is that [an allergist] could use milk powder from a lot of different sources. And you may get different results because there they aren’t as well-regulated and those results can be either good or bad.

They could maybe put patients at risk for more allergic reactions or maybe put them at risk for less efficacy, or they could do the opposite.

I think trying to come up with some concepts – for example, if we’re going to do milk oral immunotherapy, these are three to five potential products that we feel fairly comfortable with while we’re waiting for FDA approval of a standardized product.

The second is to articulate a bit better the potential risks involved in oral immunotherapy, so that we could come up with some standardized language for the consent form, since patients should all be giving informed consent before they undergo oral immunotherapy. What’s in a consent form isn’t regulated if I’m not doing a clinical study. Having some guidance for practitioners, so they can inform their patients a little bit better, would also be good.

Some of the private practice allergists have found in that using a biologic such as Xolair to try help to dampen down the immune system, while not extensively studied, seems to be working in some patients. Do you also see trying to develop guidance for that type of protocol as well?

TC: I would suggest that we look at that, but there are a number of questions involved in that approach that we need some better answers to. By perhaps coming up with the right questions, we can get the information that we need to better informed patients and physicians on how to do this.

Xolair, as you’re aware, has been approved for asthma for 15 years. It was studied for food allergies as a standalone a long time ago, and fell out for while. Now it’s back, either as a standalone or to help to protect patients who are undergoing oral immunotherapy.

But what don’t we know about it? Well, once we get somebody up to maintenance dose on the oral immunotherapy, we don’t know definitively: ‘Can I stop the Xolair in all cases?’ There are reports that show you can, but we don’t know that for sure.

We don’t know also how long you would want to treat with both, and we don’t know whether or not the effects of Xolair are additive to the oral immunotherapy in protecting people from food allergy-induced anaphylactic symptoms. Intuitively, we would expect it to be, but we only have small reports. So it’s a bit hard to answer all those questions.

Is there anything else you wanted to mention to our readers?

TC: The other thing to mention in relation to oral immunotherapy is that we do have the FARE Patient Registry for those with food allergy. We would like to get to the point in that registry of seeing if we can collect the right information to get a better assessment of the safety and efficacy of oral immunotherapy, and what’s really going on in practice. So those are things that we are also working on. [He adds that information pulled from the registry is all ‘de-intentified’ data, to ensure privacy.]

There are many things that were working on over the next six months to a year. I think we’re all excited that we have a couple of potential products that are going to come out for peanut – the epicutaneous immunotherapy [Viaskin peanut patch] as well as the Aimmune product.

But that’s only a first step. I think what we want to do as an organization is to really move the field forward, and to provide a good education for the patients have food allergies to help them navigate the psychosocial issues and the medical issues associated with food allergies.

Last note:

As if to underscore the divergence of opinion on OIT, the announcement of the Food OIT in Practice Summit followed the release in late April of a controversial study analysis of peanut OIT. That analysis, published in The Lancet, came to the conclusion that, based on the risk for an allergic reaction in OIT studies, avoidance was still a better approach to managing peanut allergy than the desensitizing therapy.

“What The Lancet review does not fully explore is the long-term impact, benefits and protection that can be achieved through this therapy in relation to the risks involved with OIT,” Dr. Casale said in FARE’s press release about the summit. He agrees, though, that research is still needed to find the best candidates for OIT.