The very positive findings for what could become 

the first US Food and Drug Administration (FDA)-approved peanut allergy drug

 are historical for their success, but not for their practice.

®, Simon Murray, MD, an internist from Princeton, NJ, discussed the findings of the PALISADES phase 3 trial assessing investigative oral therapy AR101 for the preventive desensitization of peanut allergies in patients. The trial results, which were initially presented at the 

2018 American College of Allergy, Asthma & Immunology (ACAAI) annual meeting

 in Seattle, WA, come in short time before the 

anticipated FDA new drug application submission

If it were approved for peanut allergy care, it will mark a major breakthrough in allergy-related treatment. But, Murray noted, it's not the first drug to address desensitization.

What were the biggest takeaways from the phase 3 PALISADES trial results for AR101?

Murray: It's a really exciting study, because it may answer—in part, at least&mdash;a problem that is rather common in our society and is troublesome to a large majority of children. In fact, peanut allergy, which is what this drug addresses, affects about 1 in 50 young children between the ages of 4 and 17, which turns out to be about 1.5 million people in the United States alone.

But it is increasing at a quick rate in this country, as well as other industrial countries. Not only peanut allergy, but allergies in general.

What are your thoughts on it being efficacious solely in the pediatric population?

Yeah, that was interesting. It did not seem to have any clinically significant benefit in children older than 18 they were included in the study. This particular study involved 550 individuals who had been pre-selected because they were sensitive to small amount of peanut allergen.

About two-thirds of the group were under 17 I believe, and the rest were over 17, up to the age of about 50. But no benefit was seen in that older population. Yeah, allergy is a very complicated subject, but the attempt to desensitize people to allergies has been going on for a 100 years and historically, allergists have used subcutaneous preparations of small doses of allergens and increasing them on a regular basis over long periods of time to build tolerance to those allergens. And more recently, scientists have used oral mechanisms to try to treat food allergies, particularly subcutaneous preparations and oral preparations, with mixed results.

So in general, there haven't been great oral desensitization trials yet ,and this particular trial was a more favorable trial than many other trials using oral desensitization. But other forms of these sensitization are well-known and have been used for many, many years.

Simon Murray, MD: Biggest Takeaways from New Peanut Allergy Trial

The introduction of a peanut allergy therapy to US markets would make a difference in the lives of about 2% of children—lives burdened by limited diet and lifestyle options, and a fear of anaphylaxis.

Even if the best-case results from a therapy such as 

Aimmune Therapeutic’s investigative drug AR101

 only entail pediatric desensitization, Simon Murray, MD, would consider that a big win.

American College of Allergy, Asthma & Immunology (ACAAI) annual meeting

the Princeton-based internist discussed the public health concerns surrounding peanut allergies.

What is the current state of peanut allergies as a public health issue?

Murray: Well, the standard of care now to treat peanut allergies is avoidance. And if you can't avoid it, then you treat it with epinephrine, because among the reactions that people get to peanuts is anaphylaxis. It's not always anaphylaxis, but they can be quite severe reactions, and anaphylaxis can kill you. You can imagine the dilemma it presents to parents and to children who have this problem, because it’s unpredictable—the peanuts are ubiquitous in food and it takes very small amounts to cause reactions.

So, children have to be very careful about going to restaurants, as an example. Parents have to be very diligent about children that when they attend birthday parties, or even when they visit relatives. It can be burdensome to the children themselves, who get targeted often because they're different than other kids.

Not only is it unpredictable, but it's quite severe when it happens, so it affects parents and children to a great degree—and school systems. The school has to be educated about what can happen, and have to know about these things in advance.

So it's rather complicated, and if you consider the fact that it affects 1 in 50 children, it's going to happen in a school system, a kid is going to have a reaction. It's quite scary, actually, when you see it. I happen to have seen anaphylaxis personally and it's frightening how quickly it develops and how threatening it is to a person's health.

Is there potential for AR101 to increase pediatric patient allergy tolerance through adolescence?

Unfortunately, the ability to desensitize is not sustained, at least now. In a study that was unrelated to this one, other researchers have demonstrated that oral desensitization will go away in as little as 7 to 10 days if that stimulation is not maintained, so it is probably going to be a lifetime of desensitization. Now, I will note that about 20% of people who have food allergies or peanut allergies, they go away when people become adults.

But for 80% of children, they may persist for indefinite periods of time. It’s going to be a lifetime of work, and once you skip for a period of time then you're back to square one.

Simon Murray, MD: Pediatric Peanut Allergies in a Real-World Setting

The intricacies of managing a pediatric peanut allergy are exhaustive and burdensome for both the patient and their parents. As Simon Murray, MD, an internist in Princeton, NJ, noted to 

 in an interview, everyday activities such as going to a friend’s house or out to a restaurant for a meal can be a risk.

With the newest data on investigative drug AR101, presented at the 

 in Seattle, WA, showing significant benefits of desensitization in pediatric patients highly allergic to peanuts, such challenges could be eventually cleared by one daily oral therapy.

What do the benefits of AR101 for pediatric peanut allergy equate to in a real-life setting?

Murray: What's interesting to note is that it takes very small of peanut to cause allergies. In this particular study, to be included in the study, you had to respond to a 100 mg or so equivalent of peanut allergen. Now, a peanut is about 300 mg of allergen, so that was like one-third of a peanut—kind of a small amount of peanuts.

But many people react to much less than that. The FDA, the United States government have no standard now to call a product peanut-free. But for gluten, as an example: 20 parts per million is the standard minimum dose to  call a product gluten-free. Keep in mind what a part per million is: if you dissolve 4 drops of ink in a 50 gallon drum of water and stir it, that would give you one part per million of ink—very small amount of ink.

And so if you translate the parts per million into 100 mg of peanuts it's going to be something like 20 drops of that solution, I think. That's a very small amount. So therefore, people have to be very careful about going to restaurants where food is prepared, because very often when they clean surfaces or clean utensils, peanut residue gets left on them or on the countertops, or people may put peanuts on and then take them off, if they know the person is allergic—thinking that's enough. That's not.

Your restaurant workers are ignorant as to how little it takes to be sensitive to peanuts. It's a big problem for parents. Some of the advocacy groups recommend interviewing restaurant staffs and getting detailed lists of foods that they prepare, and avoiding restaurants like Asian restaurants, where they’re more likely to use nuts in preparation, or to avoid restaurants that are high-volume, fast-paced restaurants where they serve a lot of customers quickly.

But they recommend interviewing the food servers, and the chef, and the owners of the establishment. I mean, to me, that's a rather difficult thing to do. And then when the kid is not around you, you don't know what they're going to be exposed to. It really takes a lot of education and diligence.

So, this is a potentially great breakthrough, as a matter of fact. Should these oral desensitization products turn out to be positive—and it looks like they helped a significant amount of the people during the desensitization process&mdash;it could potentially help quite a few people. It is an exciting breakthrough.

As I said, most desensitization has been done subcutaneously, rather than oral, because the oral desensitization has not been really successful. Even when products are used sublingually, they don't work as well. But this product looks like it had a significant, robust effect to desensitize children who are sensitive highly sensitive to peanuts.

Simon Murray, MD: How Peanut Allergy Drug AR101 Could Change Patients' Lives

Severe asthma and peanut allergy. If Payel Gupta, MD, had to boil down the wealth of insights she gleaned from this year’s annual meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in Seattle, she’d showcase the new therapeutic options that are changing (and are soon to change) the face of treatment for patients with those 2 conditions.   

Payel Gupta, MD, allergist and immunologist, ENT & Allergy Associates, national spokesperson for the American Lung Association:

I think that there are 2 topics that resonated throughout the conference. The first one I'd say would be asthma and where we've come in asthma treatment options over the last 20 or 25 years.

We've gone from using oral steroids to inhaled steroids to inhaled steroids with a combination of long acting beta agonists, to now having these biologics that are out there that we can use to really tailor treatment based on what our asthma patients' profile is.

I think that is super exciting for us as allergists and asthma specialists. It's going to give us options for those severe asthmatics that didn't really have options before who were on chronic steroids, oral steroids for forever, which can lead to so many different negative consequences. We're excited about having different treatment options for these patients and being able to tailor therapy.

The second theme that I think people are really excited about is the new desensitization options that are going to become available in 2019. We hope! One of them is a peanut desensitization patch, and the second one is a powder base oral immunotherapy for peanuts also.

That's super exciting because right now all we have is avoidance measures for our patients. to be able to offer something else to patients is going to be a game changer.

There are physicians out there that are doing oral immunotherapy in their offices but it's not really standardized, it's not FDA approved and not all allergists feel comfortable doing that. So with 2 treatment options that are actually FDA approved, we're going to be more comfortable and I think that patients are just going to have more options and feel safer.

Top 2 Key Takeaways from ACAAI 2018

If the US Food and Drug Administration (FDA) were to approve Aimmune Therapeutic’s investigative AR101 drug as the first therapy for peanut allergies next year, how long until the market sees a competitor drug?

Food allergy is a difficult field to both treat and test drugs for, Simon Murray, MD, a Princeton-based internist, told 

The risk of anaphylaxis—or even death&mdash;in the necessary involvement of patients’ allergies in clinical trials can limit researchers’ patient pools.

That’s not to say peanut allergy care is a field solely ventured by Aimmune. Following the company’s presentation of its newest AR101 data at the

 American College of Allergy, Asthma & Immunology

 (ACAAI) annual meeting in Seattle, WA, Murray detailed the brief history of research in peanut allergy care—and the hurdles other researchers have faced.

Can food allergy therapies become a competitive drug market?

Well, this has been studied for 10 years, at least. A group in Cambridge, England, had developed a standardized formulation of peanut extract that came from defatted peanut flour, and they were able to, with precision, measure how much protein was in a given amount of this protein powder. So based on that work, this latest group came out and did their studies based on using defatted peanut flour.

And they were able to very precisely measure specific amounts of peanut proteins—even 0.3 mg, to 1 mg, to 10 mg, to 30 and upwards&mdash;because you have to use a standardized solution, and it has to be done in a very careful environment. In this study, one patient had to be admitted to the hospital during the process of the study, and there was about a 15% dropout rate because of adverse reactions.

You can just imagine the difficulty of enrolling patients in a study like that. Who would want to enter a study where you’re going to get the possibility of anaphylaxis? They're going to give you substances that could potentially kill you. So, the study had to be started in a hospital setting and later continued as outpatients. It had to be done with very carefully measured amounts of this protein. And this was a breakthrough—that the Cambridge group was able to find a way to document how to give carefully measured amounts.

And it has to be done pharmaceutically. You can't ask people to dilute stuff, and I just don't think it will work.

Simon Murray, MD: A Competitive Food Allergy Therapy Market

With all the different treatments available for patients with severe asthma, how can physicians choose the one that’s right for their patients? According to Payel Gupta, MD, of ENT & Allergy Associates in Brooklyn, NY, the decision hinges upon an intimate knowledge of type of asthma and an intimate knowledge of the patient.

With our severe asthmatics we're able to figure out what their phenotype is. Are they allergic? Are they allergic and eosinophilic? Are they steroid dependent? Some of those types of asthma tend to overlap.

As allergists now, with all of these different treatment options, we have to figure out which one to pick. There are a lot of products that've just come out for, specifically, eosinophilic asthma and I think as a practicing clinician, it's just about figuring out which one you should choose, and that's the biggest conundrum for all of us.

We talk about that a lot among ourselves. So what are you guys using? What've you had good benefits with? All that kind of stuff.

The one thing with dupilumab is that it's going to be administered at home. That's one kind of bonus point for that treatment option is that patients will actually administer it to themselves at home.

That has its pros and cons. With any kind of patient, you want to know that they're taking their treatments, so having them use an injectable at home, compliance is potentially going to be an issue. Whereas, other options where they have to come into the clinic, you know that they're not showing up, you know that they're not coming in, so you can be on top of them a little bit more.

There are pros and cons. It might be more convenient for more patients to do it at home, but then as a physician, you're worried about their compliance.

I think that some people are talking about whether you can use 2 biologics at once, and that hasn't been studied. There's not going to be a company that's going to pay to study their drug with another drug. So there are certain patients that might fit using something like Xolair and something like Dupixent, so using both of those medications at the same time.

Right now I think it comes down to what the insurance plan might cover. That's my first thing when I have somebody with eosinophilic asthma: let's find out from their insurance what their preferred drug is, and then look at that preferred drug and see if it makes sense for the patient.

Talk to the patient also. Talk to them and figure out what they want. Do they really want something that they can inject at home, do they mind coming into the office? There's also an IV option, and so finding out which option for them feels safer.

It's talking to the patient, looking at insurance coverage, and then kind of going with the other details that we all figure out as we use the medications more and more.

Payel Gupta, MD: Choosing the Right Treatment for Patients with Severe Asthma

With so many new therapies available for patients with severe asthma, the array of treatment options has never been stronger. However, getting these patients to adhere to their prescribed asthma medications is an entirely different challenge than choosing the asthma therapy that fits the diagnosis. When it comes to severe asthma management, it's all about finding the middle ground. 

Adherence is huge for us. No matter what area of medicine you practice, you want to know that your patient is taking the medication. I always tell my asthmatics this: If you're not using the treatments, then I'm just going to keep adding more. I'm just going to keep giving you more, I'm going to keep increasing the dose, and I'm going to keep trying to figure out why the treatment's not working.

It turns into a bigger problem once we start doing that, because then the patient has even more medications and then they start using one, but not the other, and it turns into a big mess.

Adherence is something that we constantly talk about in medicine, and how we can improve patient adherence. I think talking with the patients and coming up with a plan together, versus just throwing stuff at them is one of the most important things that I think helps with adherence.

Figuring out what their schedule is like, what makes them nervous. Some patients won't tell you right off the bat, "Hey, I don't want to use a pill," or "Hey, I don't want to use an inhaler," or "I don't want to use a nasal spray," because they've had negative outcomes or they've experienced some side-effects that they didn't like.

So you have to talk to them. Does this make you comfortable? Are you OK with this plan? Are there any questions that you have?

A lot of us are also talking about how often you call, or have your nurses call patients after a week and check in on them, or 2 weeks, and how quickly do you follow up with them during an actual office visit?

There's no written protocol for any of this stuff. You kind of figure it out as you go along. What works for your practice, what works for your patients and what makes you feel comfortable.

Patient compliance improves when they feel like they had an option, and when they feel like they were a part of that decision in which therapy to use.

And then obviously cost is also a huge issue, and I have patients that I'll ask, "Why aren't you taking it?" And they say, "Oh, well it costs like $150, doc, I can't afford that!"

Just let me know. We have no idea when we send the prescription what their copay is going to be. Part of my initial spiel to people is that when you get to the pharmacy, if it's super expensive, if they say it's not covered, if you're paying over 50 bucks for anything, I want to know.

Maybe there's something else that your insurance plan likes better, and it's the same as the other medication that I want to use, so we can use the other alternative. There are so many options now, and that's why it gets confusing for the doctors and the patients.

Payel Gupta, MD: Improving Adherence in Patients with Severe Asthma

Asthma is often understood by laypeople to be easy to live with compared to more serious conditions like cancer or cardiovascular disease. But the condition has its own unique challenges for patient and practitioner alike, and physicians must be aware of them in order to provide the best care possible.

Data shows that patients with asthma often become victims of bullying and social isolation, which can cause a ripple effect that lasts a lifetime. Enduring that harsh behavior during development can lead to depression, and depressed patients are less likely to adhere to their treatments, which leads to worsening asthma symptoms and so on.

It’s important that pulmonologists, allergists and immunologists consider the effects that depression may be having on their patients with asthma, according to Payel Gupta, MD.

I went to an asthma lecture and they were talking about how they use a depression inventory scale with all their asthmatic patients. Depression is a huge player in how compliant patients are going to be and how patients perceive their disease. 

Especially for asthma, it's a very emotionally-based disease. I thought it was really interesting that some practitioners were using these depression inventories to kind of know where their patients are at, and then going to the next step, which is referring their patients to a psychologist or to a psychiatrist for whatever it seems like the patient might need to help them with that aspect of their health. 

I thought that that was interesting and I'm going to try to implement that in my severe asthmatics.

Payel Gupta, MD: Managing Comorbid Asthma and Depression

California is recovering from a nightmare wildfire season; dozens died, thousands were displaced and hundreds of thousands of acres were burned, taking out entire communities.

For hundreds of miles beyond the burn areas, skies went dark for days and the air was thick with smoke. Even healthy residents were advised to stay inside. For 

Debbie Dobrosky, a 67-year-old Riverside County resident with chronic obstructive pulmonary disease (COPD), 

 that even inside her apartment she had to use her inhaler twice on one August morning, “which is not a normal thing."

"Today I'm stuck inside,” she said, “there's no going out."

 with COPD, about a third of which are over 65 years old. Another 

 have asthma, which affects about 1 in 12 people across the country.

Coming from a family of physicians, some who are working in California, the same issues have been coming up in our conversations recently. How do we as a medical community better prepare for wildfires? How do we allow patients to continue their lives without major interruptions? And how do we prevent chronic illnesses from flaring up and risking lives?

These questions are especially pressing as millions of our patients are being told that this is the 

 in the western United States. Wildfire season is 

 around the world, the number of major wildfires in the Great Plains has 

 and structures lost to wildfire in the American west has 

During a brief respite before the next series of wildfires begins, everyone from physicians to policymakers, insurance companies, healthcare executives and tech companies should be racing to develop and disseminate medical solutions that will save lives in the years to come.

 that physicians should be advising their patients to take, like staying inside as much as possible and controlling the environment indoors. If your patients are using an air conditioner, advise them to close the fresh-air intake so smoke isn’t coming inside. Help them appreciate the benefits of buying an air cleaner with a HEPA filter to clean the air. Ensure that your patients aren’t smoking inside, burning candles, starting fires or using a gas stove.

If your patients must go outside, let them know to wear a particle respirator mask, which can filter out 95 to nearly 100% of airborne particles. (The Centers for Disease Control and Prevention has a 

 here of what people should be looking for in a respirator mask).

But this advice still leaves patients largely on their own when the fires sweep through and they shut themselves indoors. For physicians with hundreds of patients, it means hoping that they are following your advice and not meeting unexpected problems.

So how can we keep an eye on patients? How can patients and physicians track in real time how air conditions are impacting health?

That’s the question we are working to answer at Adherium, where we have developed a technology solution called 

, for people with chronic respiratory disease. Our solution includes a sensor that attaches to an inhaler and wirelessly transmits usage data to both patients and physicians, allowing them to track it in app and web-based dashboards.

The device reminds patients when it’s time for a dose, but it can also provide crucial information that allows physicians to intervene before breathing difficulty progresses to something much more serious. In the process of monitoring and tracking therapy usage, physicians also get lots of other information about what sort of challenges the patient is experiencing in terms of their environmental.

This information can be used to make sure patients are following best practices to prevent wildfires from making their breathing problems even worse. Are they wearing their mask properly? Have they closed off air intake on the air conditioner? Do they have enough doses on hand to make it through the next few days?

The idea that wildfires are the new normal is hard to accept for anyone living in high-risk areas. But the anxiety is particularly severe for those worried they won’t be able to breath every time the smoke starts to spread.

We have the tools to help. Let’s make sure we are ready to use them the next time the fires flare up.

is clinical business development lead at 

 a digital health platform focused on medication adherence for people with chronic respiratory disease. 

How Physicians Can Help Patients with Asthma Prepare for the Next Wildfire Season

When your colleagues and patients think of deadly diseases, where does their mind go? Heart disease, cancer, and stroke tend to top the list, and there’s no doubt that they’re a heavy burden on health systems, patients and society.

Asthma, on the other hand, might not even crack many people’s top 50, and that can be problematic, according to Payel Gupta, MD. “There’s still a huge burden of disease in this country,” she told 

While treatment options have expanded and outlook for adherent patients has improved, there seems to have been an opposite reaction in terms of people’s understanding of the condition. Children with asthma are more likely to be bullied and isolated from their peers, often because of misconceptions about the condition. As a result, many patients with asthma avoid their treatments for fear of being stigmatized, which makes poor outcomes more likely.

Tackling asthma treatment with this in mind can go a long way toward improving adherence and outcomes, Gupta said.

Asthma doesn't get [the attention it deserves.] People say, "Oh, I have asthma." A lot of people just kind of blow it off. But it still accounts for a lot of deaths in this country.

Even with all the treatment options we have available, there's still a huge burden of disease in this country. Not only the emergency room costs for patients going in constantly for their asthma exacerbations but then patients actually dying from asthma.

I think that people kind of downplay their asthma sometimes a little bit, because it's just kind of a common thing. "Oh, I just have asthma." But there's different variations of asthma.

When I was listening to the lectures, they started talking about how they started this big asthma study in 1994. They built this group of people that started to really look at asthma and how we can better treat it. And my mom passed away from an asthma attack in 1991, so sitting there and seeing that she passed away in 1991 and everyone started realizing that "Hey, there's something going on here. We're not treating these patients the way we need to be treating them, and this is a bigger deal than we thought. Something that we're doing doesn't seem to be working."

It's kind of interesting to see how has kind of evolved - the history of asthma and how it just continues to get better and better with new treatment options.

Payel Gupta, MD: Asthma Doesn't Get the Attention It Deserves

The following case study was presented at the American College of Asthma, Allergy and Immunology (ACAAI) 

: Inducible urticarias such as cholinergic or adrenergic urticaria (AU) can be challenging to control. Herein, we report an index case of AU successfully treated with omalizumab.

: A 17-year-old female with a history of Ehlers-Danlos syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome presented with diffuse pruritic evanescent welts with erythematous centers surrounded by white halos (Image 1) unresponsive to several therapies including a combination of high dose H1-antihistamines, H2-antihistamine, and leukotriene receptor antagonist in addition to a low dose beta-blocker. Due to the severity and frequency of the hives, omalizumab 300mg subcutaneous injections were initiated every 4 weeks resulting in complete resolution shortly after the first injection. She continues to maintain good control months later with no reported breakthrough episodes.

: AU is a rare form of urticaria first described in 1985, distinct from cholinergic urticaria. Although the exact mechanism of AU is unknown, it is believed to be provoked by a stress-induced concomitant release of epinephrine and norepinephrine. Diagnosis can be made by intracutaneous injection of adrenaline or noradrenaline, which produces the characteristic eruption. In this case the patient’s diagnosis was based on clinical history and classic presentation of red papules surrounded by white halos. Although AU typically responds to trigger avoidance, H1-antihistamines and beta-blockers, when these treatments fail, additional therapeutic alternatives are limited. This is the first case demonstrating that AU can be successfully treated with omalizumab which should be considered as a treatment option if first line agents prove ineffective.

Omalizumab is the only biologic currently approved for both allergic asthma and chronic idiopathic urticaria (CIU). It “has long been an important treatment option for people with allergic asthma and CIU,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech, the therapy’s manufacturer. Horning added that omalizumab (Xolair) has been used to treat 

 of 67 published reports on the real-world effectiveness of omalizumab demonstrated that its benefits and safety for the treatment of CIU in the real-world met or exceeded results gleaned from clinical trials. The meta-analysis was not the first instance of real-world success for the therapy. In September 2017, it was also shown to 

 in the real world as a treatment for asthma.  

 by the US Food and Drug Administration (FDA) in mid-August 2018 as a subcutaneous injection for the prevention of severe food allergy reactions.

Omalizumab was granted the designation to expedite its regulatory development and review as a potential therapy for serious or life-threatening conditions. The designation was based on data from 7 clinical trials over the past decade which assessed omalizumab’s efficacy and safety versus various food allergens such as peanut, milk, and egg.

Case Study: A Rare Form of Inducible Urticaria Successfully Treated with Omalizumab

New study results on the immune profile of healthy human skin across various body areas could have significant implications for the treatment of 

 and other immunological disorders with epicutaneous immunotherapy (EPIT).

 Inflammatory Skin Disease Summit (ISDS) in Vienna, Austria this week, Dr. Ester Del Duca of the Icahn School of Medicine at Mount Sinai shared the results of a trial showing notable differences in cell type distribution and immune profile of healthy individual’s skin.

Del Duca and team’s investigation assessed 4 locations—inner upper arm, upper back, outer upper thigh, and lower abdomen&mdash;for regulation of the T helper cell 2 (Th2) and Th17 pathway genes, plus regulatory T cells. Both markers are critical targets for allergic reaction prevention, according to the investigators.

Of the observed locations of skin, upper back region showed the greatest regulation both Th2/Th17 pathway genes and regulatory T cells, the greatest rate of dendritic and Langerhans cells, and the lowest expression of negative immune regulators. Investigators believe this makes it the region most likely to conduct immune recognition of antigens in allergy patients treated with EPIT.

The findings have particularly crucial implication for DBV Technologies, the France-based biopharmaceutical firm which submitted a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) in October for its EPIT therapy Viaskin Peanut—a pediatric peanut allergy treatment scheduled to receive FDA decision in early 2019.

The investigative patch was designed to deliver a small amount of peanut protein via patients’ backs to the immune-system Langerhans cells, thereby desensitizing patients to peanut allergens. Its application to the FDA is supported by both Breakthrough and Fast Track Designations from the FDA, as well as clinical evidence showing 250 mcg therapy significantly desensitizes peanut allergy in patients aged 4-11 years old versus placebo.

If approved, Viaskin Peanut can be the first FDA-approved therapy for the life-threatening chronic allergy that currently affects about 1.5 million children in the US.

2019 could potentially be a booming year for advancing allergy care. Along with the EPIT skin patch therapy, investigative oral peanut allergen drug AR101 from Aimmune Therapeutics is anticipated to submit an application to the FDA in short time—1 month following a series of promising study results being presented at the 

American College of Allergy, Asthma & Immunology (ACAAI)

In long-term cohort analysis of the phase 3 PALISADES trial

, about two-thirds (67.2%) of pediatric peanut allergy patients to receive AR101 300 mg once-daily therapy were capable of ingesting a 600 mg-plus peanut protein without dose-limiting symptoms after about 24 weeks. Among patients to receive placebo, just 4% were capable of the same ingestion (95% CI: 53.0 — 73.3; 

, centered on assessing the treatment satisfaction for patients and parents included in the PALISADES study, reported that AR101 was mostly favorable in treated patients while also showing positive impacts on their quality of life.

, Princeton, NJ-based internist Simon Murray, MD, noted how burdensome peanut allergies can be for pediatric patients and their families. The amount of “education and diligence” that goes into monitoring the highly dangerous condition makes the development of desensitization therapies all the more critical.

“Should these oral desensitization products turn out to be positive—and it looks like they helped a significant amount of the people during the desensitization process&mdash;it could potentially help quite a few people,” Murray said. “It is an exciting breakthrough.”

Regarding the new skin immune profile trial results, Hugh Sampson, MD, chief scientific officer of DBV Technologies and Kurt Hirschhorn Professor of Pediatrics at Icahn emphasized the significance of the back being proven to be the most immunological-responsive area observed by investigators.

“Such data help ensure that novel treatments are optimized in the real-world and further support the therapeutic benefit that children with peanut allergy may receive from treatment with Viaskin Peanut, which is applied directly to the upper back,” Sampson said in a 

The study, "Major Differences in Expression of Inflammatory Products in Skin from Different Body Sites of Healthy Individuals," was presented at ISDS 2018.

Skin's Immune Profile Bolsters Benefits of Potential Peanut Allergy Patch

The following case study was authored by Jasmine Alsukhon, MD, and presented at the American College of Asthma, Allergy and Immunology (ACAAI) 

: Adalimumab is an anti-tumor necrosis factor monoclonal antibody effective in treating autoimmune and inflammatory diseases. Although adalimumab is fully human and considered of low immunogenicity, there have been rare reports of local and systemic

: A 17-year-old male with Crohn’s disease failed infliximab therapy and was switched to adalimumab. He tolerated the first 3 weekly loading doses, but developed delayed generalized urticaria 6 hours and 24 hours after his subsequent two maintenance doses (q2 weeks), respectively, despite antihistamine premedication. Although urticaria resolved within days, he had persistent pruritus. On examination in the allergy/immunology clinic, he had localized urticaria and profound dermatographia, a new finding since initiation of adalimumab. Desensitization to adalimumab was recommended due to severe Crohn’s disease and failure of multiple prior therapies. This was done at the hospital infusion center over 4 weekly visits, with the first dose in 7 steps and subsequent doses in 2 steps, before spacing back to q2 week injections. He developed faint rash after the first desensitization visit, with no subsequent symptoms. He now self-administers the injections at home and the Crohn’s disease is in a quiescent state.

: Cutaneous manifestations of adalimumab sensitivity have been reported as immediate-type injection site reactions or psoriasis-like rash. Desensitization to adalimumab has previously been reported for immediate-type reactions, but we present successful desensitization in a patient with a more delayed and prolonged manifestation of hypersensitivity. The two-week half-life of the medication allows for maintenance of the desensitized state in between injections.

Adalimumab has topped the list of drug spending since 2011, with $13.6 billion spent in 2016 — more than $3 billion more than the next highest spend, according to data from the QuintilesIMS Institute.

Looking forward to 2021, the report detailed that while the patient use of new treatments has slowed, it is expected to continue to recover to historical highs in spending growth of $15 to $17 billion from 2018 to 2021. The exclusivity loss impact is expected to grow to greater than 50% in the next 5 years, partly as a result of patent expiries, and partly a result of the introduction of biosimilars to the market. 

The US Food and Drug Administration (FDA) accepted the Biologics License Application for a Novartis biosimilar to adalimumab in January, 2018.

 from a trial that investigated the possible extension of dosing intervals for the drug among RA patients, in order to aid individualized treatment, found that the therapy was effective and safe. 

"We think that rheumatologists should start the evaluation of adalimumab treatment by considering the pharmacokinetics in that individual patient," Merel l’Ami, MSc, from the Amsterdam Rheumatology Center and lead investigator of the study, told 

. “It will show the rheumatologist when drug concentrations are undetectable (occasionally, as a result of a large amount of anti-drug antibody formation), and it will show the rheumatologist when a patient is overexposed. Our study showed that patients can reduce the dose safely. Reducing this kind of overexposure will personalize treatment and save a lot of drug costs."

Case Study: Successful Desensitization for Delayed Urticaria to Adalimumab

The following case study was authored by K Jackson, S Bahna and D Kaufman, and presented at the American College of Asthma, Allergy and Immunology (ACAAI) 

 Little is known about potential consequences of stopping mepolizumab therapy in asthmatic patients. This is a case of a 43-year-old female diagnosed with eosinophilic myocarditis six months after cessation of mepolizumab.

 A 43-year-old female with severe eosinophilic asthma was started on mepolizumab. She remained compliant for 2 year with significant improvement of symptoms but due to a lapse of insurance coverage, therapy was interrupted. Six months later, she developed low grade fever, cough, and dyspnea with infiltrates on CXR. She was diagnosed with atypical pneumonia and treated with antibiotics without improvement. Within a few days, she developed hypoxic respiratory failure requiring noninvasive ventilation support. WBC was 26.2 K/uL with eosinophilia of 9.69 K/uL. She had elevated troponin (7.58); EKG had lateral ST elevation myocardial infarction, and echocardiogram showed pericardial effusion with EF of 20-25%. Infectious workup was unremarkable. Heart catheterization revealed normal coronaries. Pericardiocentesis cytology demonstrated 89% eosinophils. Cardiac MRI showed circumferential subendocardial hyperenhancement of left ventricle and global ventricular hypokinesis. Bone marrow biopsy and cytogenetic testing were negative. She was diagnosed with eosinophilic myocarditis and started on IV methylprednisolone with marked improvement in symptoms. The patient was discharged on high dose prednisone and heart failure therapy. Three months later, she resumed mepolizumab and has been tolerating a slow prednisone taper.

 To our best knowledge, this is the first reported case of eosinophilic myocarditis and pneumonia after mepolizumab cessation. This patient may have had a rebound hypereosinophilia or an underlying hypereosinophilic syndrome which was masked by

In one practitioner's experience, adding mepolizumab to the treatment regimens of patients with severe eosinophilic asthma in his practice resulted in improved symptoms and quality of life, similar to those reported in controlled clinical trials with screened participants.

"After extensive double-blind controlled studies, it is always reassuring to the physician in the field that the results of these studies are applicable in a private practice office setting," Ronald Strauss, MD, Cleveland Allergy & Asthma Center and Case Western Reserve University Medical School, Cleveland, Ohio, told 

Moreover, data from the longest anti-interleukin 5 (IL-5) biologic therapy trial in severe eosinophilic asthma ever reported found that mepolizumab consistently improved exacerbation reduction and asthma control in patients with the condition.

Data from the open-label COLUMBA study, presented at the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, reported the results of patients with severe eosinophilic asthma who were treated with mepolizumab for a mean 3.5 years and up to 4.5 years. Along with consistent clinical efficacy, patients treated with the drug reported safety profiles similar with previous studies.

A Case of Hypereosinophilic Syndrome After Mepolizumab Treatment 

The following case study was authored by J Freeman, C Reynolds, W Soong, and J Anderson, and presented at the American College of Asthma, Allergy and Immunology (ACAAI) ) 

 Anaphylaxis affects 1.6%-5.1% of adults. Treatment with epinephrine is generally effective, and supplementary medications can be used for prevention/treatment of anaphylactoid symptoms. Common adjuncts include corticosteroids and antihistamines. Radiocontrast is necessary for evaluation of certain conditions and cannot always be avoided even with history of reaction. While underlying mechanisms of contrast reactions are not well understood, premedication with corticosteroids/antihistamines can often be used for prevention of reactions.

 64-year-old male with DM2, hemodialysis-dependent ESRD, and known contrast reactions presented for routine fistulogram and experienced severe anaphylaxis 10 minutes postadministration of IV premedications (methylprednisolone/diphenhydramine), prior to contrast administration. Anaphylaxis resolved after epinephrine, albuterol, and fluids, and he was referred to Allergy for identification of offending agents. Prick/intradermal testing to various steroids/antihistamines was performed. Testing was positive to IV methylprednisolone succinate, IV hydrocorticone succinate, and IV diphenhydramine. Patient has since tolerated PO prednisone, loratadine, and fexofenadine.

 Our patient may have anaphylaxed to steroid, succinate, and/or diphenhydramine. Negative testing to prednisolone and prednisone-tolerance make succinate a more likely culprit than steroid, but further testing/challenge is needed to elucidate. Regarding antihistamines, this is one of few reports of reaction/positive testing to diphenhydramine with concurrent negative

testing/tolerance to loratadine and fexofenadine. Adjunct therapies for prevention/treatment of allergic reactions can occasionally trigger anaphylaxis. These medications should therefore be included in anaphylaxis workup. Allergy testing may help predict tolerability of alternative agents when similar medications are needed. Given limited reports in the literature, further studies are needed to better determine reliability of testing for these agents and cross-reactivity between them.

In August, the US Food and Drug Administration 

approved the first generic version of both EpiPen and EpiPen Jr

 (epinephrine) auto-injector for the emergency treatment of allergic reactions in adults and pediatric patients who weight more than 33 pounds.

The approval, granted to Teva Pharmaceuticals USA, indicates a generic version of the 0.3 mg- and 0.15 mg-strength injectors. The marketing is approved to include patients with life-threatening allergic reactions (anaphylaxis).

According to the FDA, anaphylaxis occurs in approximately 2% of all Americans, with those who have experienced a previous episode being at risk for another one. The epinephrine injector has been approved under several various product names over the years, and are intended for emergency patient use at the time of an event.

Scott Gottlieb, MD, commissioner of the FDA, 

 that the approval is part of the FDA’s commitment to progress patient access to less costly, safe, effective therapy options.

“This approval means patients living with severe allergies who require constant access to life-saving epinephrine should have a lower-cost option, as well as another approved product to help protect against potential drug shortages,” Gottlieb said. “The path to developing generic drug-device combination products like this one is challenging.”

ACAAI 2018 Perspectives