Why Parents Are Turning to a Controversial Treatment for Food Allergies

For families with food allergies, micro-managing daily life to avoid accidentally consuming the wrong food can be a huge burden. They scour labels. They avoid restaurants. They ban their kids from birthday parties, or refuse to enter sports stadiums, worrying that peanut shells littering the ground could trigger life-ending anaphylaxis.

The resulting angst has driven some families and physicians to try a therapy that has done well in early studies but has unclear long-term effects and is not yet approved by the Food and Drug Administration (FDA). The controversial treatment is called oral immunotherapy (OIT). Conceptually, the method works like allergy shots, which for 100 years have reliably treated pollen and other environmental allergies by desensitizing the immune response to these triggers. Instead of injecting allergens through the skin, OIT involves consuming a bit of the forbidden food each day, at gradually increasing doses, so the immune system can learn to put up less of a fight.

Over the past decade, the number of OIT providers has grown from just a handful of doctors nationwide to a small, influential cohort of more than a hundred today. Thousands of food allergy patients who have tried oral immunotherapy in the United States and abroad swear by the treatment, often calling the results life-changing. And with an FDA decision expected by early 2020 for Aimmune Therapeutics’ “peanut capsules,” OIT could soon go mainstream.

But at the moment, allergists remain deeply divided over the treatment, which doesn’t work for everyone and carries uncertain risks. In contrast, the traditional approach — avoidance of the trigger food — achieves safety for the vast majority of individuals. In fact, someone with a food allergy has a greater chance of being murdered than dying from an allergic reaction. And yet that fact belies the hidden stress and fear that grips many of the estimated 32 million Americans with food allergies. For them, the possibility of a life-ending reaction looms large, and many are eager to see the FDA approve a drug that advocates say could put those fears to rest.

But with many researchers dismissing the science as thin and the treatment unnecessary, the schism over oral immunotherapy — among both physicians and food allergy families — may not easily resolve. “This is a very weird field,” said allergist Kari Nadeau of Stanford University School of Medicine. “I’ve been in oncology. I’ve been in autoimmune disease. And just over the past 13 years I’ve been in allergy.” There are lot of different physicians with varying levels of training, Nadeau said. “It’s a little strange to have such a divergent climate.”

Though OIT is relatively new, the science behind desensitization therapy dates back more than a century, when the term “allergy” had barely entered the medical vocabulary. In 1905, a German doctor described treating “milk idiosyncrasy” in infants by feeding incrementally increasing drops of milk. Three years later, a London physician reported giving daily doses of egg to calm a teen boy’s “egg poisoning.” By 1940, clinicians had published a total of nine papers describing the use of similar methods to treat dozens of people with allergies to milk, wheat, egg, orange, tomato, and cocoa.

In the mid-1960s, scientists discovered the molecular culprit: immune-system antibodies called immunoglobulin E (IgE). Each IgE recognizes a specific allergen — ragweed, say, or peanut. When the allergen gloms on, IgE travels to other immune cells, leading them to unleash histamine and other chemicals that set off an allergic reaction in the nose, lungs, throat, or skin.

Beyond these isolated advances, food allergy research got little attention for decades. This was, in part, due to the low prevalence rate. As recently as the early 1980s, less than 1 percent of people in the United States were thought to have a food allergy. “For a long time, the easy answer was just to avoid the food if you were allergic,” said Christina Ciaccio, a pediatric allergist at the University of Chicago Medicine who has consulted and helped run studies for companies developing peanut allergy treatments.

If a reaction did escalate to something more serious, such as full-body hives, throat tightness or trouble breathing, a shot of epinephrine — FDA approved as an auto-injector under the name EpiPen in 1987 — could start to bring relief within minutes. As manufacturing practices changed, Ciaccio said, people started eating more processed foods, and it became increasingly difficult to avoid accidental allergen exposures.

In the late 1980s, initial reports of anaphylactic deaths due to peanuts trickled into the medical literature. In 1992, Denver physicians published a small study in which they treated food allergy patients with skin injections, the approach routinely used for environmental allergens. But the study came to a halt when a formulation error caused a subject in the placebo group to die of anaphylaxis. “That slowed food allergy research for over a decade,” said Ciaccio.

While research stagnated, media stories brought the terror of food allergies into the public consciousness. In 1995, The Wall Street Journal ran the headline “Peanut Allergies Have Put Sufferers on Constant Alert.” Later that year, a British daily tabloid newspaper published a story titled “Nut Allergy Girl’s Terror; Girl Almost Dies from Peanut Allergy.”

In the years that followed, for reasons not well understood, food allergies became more common among U.S. children. Between 1997 and 2008, peanut allergies more than tripled. In 2002, as part of the first state guidelines for managing food allergies in schools, Massachusetts called for peanut-free lunch tables. In a span of about 15 years, peanut allergies had risen from a virtually unknown medical condition to what some might call a public health emergency. Today, food allergies affect 8 percent of kids in the U.S. and more than 10 percent of adults.

In 2005, five research centers received a National Institutes of Health grant to form a consortium to conduct basic research toward developing food allergy treatments, and to run clinical trials to test them. “We were scared to do peanut,” said A. Wesley Burks, a pediatric allergist at the University of North Carolina School of Medicine and one of the consortium’s lead investigators. Evidence suggests that the vast majority of life-ending food allergic reactions are caused by peanuts or tree nuts.

So as a proof of concept, the consortium’s first oral immunotherapy studies were done with egg. Burks and colleagues conducted a study showing that daily doses of powdered egg white could help people with egg allergy. The method was not a cure. But when the study ended, most participants could tolerate enough egg protein to withstand accidental exposures. In other words, they became bite-proof.

The team then enrolled 39 people in a peanut OIT study using a similar protocol. Those who made it past the initial day consumed store-bought peanut flour — which was pre-measured and sterilized in the lab, then mixed at home into applesauce or pudding or other foods. Dosing started at 50 milligrams and went up 25 milligrams every two weeks. (A few participants had to start at a lower dose and had their increases adjusted accordingly.) Once participants could tolerate 300 milligrams of peanut protein — a little more than one peanut — they began a maintenance phase, steadily increasing their daily OIT dose up to 1800 mg over the next few years.

Nearly a quarter of the original participants ended up withdrawing from the study. Four dropped out because of allergic reactions to the therapy, and gastrointestinal or asthma symptoms. The rest withdrew for other reasons, including transportation issues, parental anxiety, and failure to perform home dosing. But among the 29 participants who finished, 27 successfully passed an oral food challenge with 3.9 grams of peanut protein (about 16 peanuts).

As that initial wave of OIT publications came out, a smattering of private-practice allergists saw an opportunity. They recognized the principles and basic procedures as similar to the allergy shots they routinely administered for airborne antigens. “Any trained allergist would know how to recognize and respond to a reaction,” said Richard Wasserman of Allergy Partners of North Texas. Whether triggered by peanut or pollen, “an allergic reaction is an allergic reaction.”

Chatting with an El Paso colleague who was among the nation’s first allergists to administer private-practice OIT, Wasserman was inspired to develop protocols for his own clinic. Wasserman started treating patients in July 2009 and he and the colleague presented their early OIT experiences in a 15-minute oral poster session at a national immunology meeting a few years later.

“The room was overflowing out the door,” Wasserman recalled. His results were eye-opening and would soon be backed up by published studies. Among individuals who try OIT, about 80 percent become bite-proof.

In such reports of preliminary results, many parents saw a potential escape from daily struggles characterized by fear, isolation, and invisibility.

Shea Tritt discovered her son’s peanut allergy when he was 13 months old. Moments after licking peanut butter off her finger, he broke out in hives, his eyes and face swelled, and his tongue got “so big he couldn’t close his mouth,” she said. From that point, “I was just so petrified of reliving that moment that I just cut off anything new,” said Tritt, a gymnastics coach in Abingdon, Virginia. Her son has never tasted an orange. “I think he kinda learned, this is what I eat, and we stayed in that really small box.”

Alicia Bales’ son is allergic to dairy, egg, some tree nuts, and some seeds. She worries about an allergic reaction, she said, but her son’s condition has affected their family in other ways, too. Last Thanksgiving, she made a batch of her grandmother’s special egg noodles with her daughter. Her son, Ethan, wanted to play with the dough. “I couldn’t let him,” said Bales. Since Ethan’s diagnosis, some foods now signal danger rather than safety, illness instead of nourishment, fear rather than comfort, Bales explained. “There’s a source of love from my past that I can’t pass on to my son.”

Families dealing with food allergies also report feeling misunderstood because people tend to lump their life-threatening condition in with a slew of other diets, health concerns, and ethical reasons for restricting certain foods. To help others understand, food allergy patients may stress that they have a “life-threatening” food allergy, Ciaccio said. “These individuals then get unfairly called out for hyperbolizing.”

Sometimes the most painful misunderstandings occur within extended families. “They’re navigating aunts and uncles, sometimes even grandparents, who don’t get it — or they get it and choose not to respect the guidelines. And so that’s another source of potential anxiety,” said Tamara Hubbard, a licensed counselor in the Chicago area who works with food allergy families and maintains a website that includes a directory of nationwide food allergy counselors.

Bales often has to remind her father-in-law about her son’s allergies, sometimes multiple times a day — explaining that dairy is found in ice cream and many baked goods, and often in chocolate. She doesn’t blame him, she said, because he didn’t grow up around food allergies. When her son first got diagnosed, Bales said, she felt as though he was playing at the edge of a cliff: “No one could see the edge except for me.”

For some, oral immunotherapy offers a sense of control. Parents want “to do something about it right now,” Bales said — even when a treatment carries a high risk of unpleasant side effects.

They hear stories and read medical reports about success with oral immunotherapy and “then they start questioning their allergist or physician: Why can’t I take it?” said Thomas Casale, chief medical advisor for operations at Food Allergy Research & Education (FARE), a non-profit that helped launch Aimmune.

The answer differs vastly, depending on the physician. Some insist that OIT is still experimental and needs further study to ensure it works consistently and safely. Others contend they have enough experience treating environmental allergens to configure an approach for desensitization to foods. “Those are the two different arguments, Casale said. “There’s merit with both.”

Over the years, these two camps have grown more vocal. In 2010, researchers in the NIH-funded consortium published a commentary titled “Peanut Oral Immunotherapy (OIT) is Not Ready for Clinical Use.” On multiple occasions consortium investigators and Wasserman have taken the stage at national meetings, debating OIT’s pros and cons.

Because food allergy rates have risen dramatically in just a few decades, the divide is in part generational. “I think some people are guarding the old,” said Nadeau, who directs the Sean N. Parker Center for Allergy and Asthma Research at Stanford University, which has helped conduct trials of food allergy products being developed by Aimmune and DBV Technologies.

Yet OIT does carry risks. An analysis of 12 clinical trials involving Aimmune capsules or store-bought peanut flour found that people on treatment were three times as likely to go into anaphylaxis compared to those on placebo or avoidance. Some experts interpret these findings, published in The Lancet in April, to suggest OIT is more dangerous than avoiding the food. “It’s one thing to say you’re willing to take risks for a treatment that’s going to offer a cure or complete resolution of the disease,” said Corinne Keet, a pediatric allergist at the Johns Hopkins University School of Medicine. “But, right now, it’s pretty clear that for most people, at least in the short term, oral immunotherapy doesn’t lead to a cure. It leads to a temporary desensitization that still carries with it a risk of ongoing reactions.”

Other doctors point to a tradeoff. When consuming a “food you’re allergic to, you’re going to have some side effects along the way. We know that. Ninety-five percent of people have side effects,” said Nadeau. But “at the end of the game, if you reach that endpoint, you can start eating food and not be worried about an accidental ingestion.”

Although oral immunotherapy can cause more frequent allergic reactions, Keet said, some families may prefer the predictability over the rarer surprise reactions that happen with avoidance.

Many experts do not consider OIT medically necessary, and very few allergists offer it. The therapy is not yet FDA approved, and has no insurance billing code, said Brian Schroer, who directs allergy and immunology at Akron Children’s Hospital in Ohio. Some allergists who offer OIT have billed it as related procedures such as an oral food challenge or a drug/venom desensitization procedure.

Plus, based on a recent analysis by the Institute for Clinical and Economic Review, it remains unclear if OIT is cost-effective compared with avoidance. “That sort of creates the ‘haves’ versus the ‘have nots,’” said Stacey Sturner, a Chicago food allergy mom whose son completed peanut OIT as a 5-year-old in 2017. Not surprisingly, the “haves” tend to be higher-income families. “OIT has ignored large segments of the patient population who have food allergy — particularly those who are poorer or ethnic minorities,” said Keet, who sees many low-income families.

Beyond cost, there’s also time and emotional burden. A treatment that requires strict compliance and many clinic visits is a significant undertaking, “especially with two working parents and multiple kids in the house,” said Edwin Kim, a father of two food-allergic children who works as an allergist-immunologist at the University of North Carolina School of Medicine. Such considerations can add to the frustration many families face when they hear about OIT. On the one hand, the treatment offers hope. But for some, it is inconvenient or even inaccessible. And it doesn’t work for everyone.

But on social media, these drawbacks are sometimes overlooked. Using the #OITWorks hashtag, some families post photos of smiling kids with OIT completion certificates and bags of peanuts, or eating birthday cake for the first time. Sturner, who started the Facebook group Food Allergy Treatment Talk, said that these voices have gotten louder over time. “That loudness really turned off a lot of people,” she said, “because it felt like shouting.”

Some parents say that doctors and journalists unwittingly fuel the shouting when they use terms like “graduation” and “failure” to describe OIT outcomes. Jaelithe Judy’s son started peanut OIT two years ago at age 13 but had to stop six months later after he was diagnosed with an OIT-triggered inflammatory disease called eosinophilic esophagitis. “I make a point myself never to say that my son ‘failed’ OIT,” said the St. Louis, Missouri, mother. Rather, she frames it as the treatment failing him. Judy said she is not alone on this point. Other families that have not benefitted from the treatment also “find this ‘failure’ language troubling and discouraging to their kids.”

Much rarer than OIT successes are food allergy deaths, which also get shared heavily on Facebook and Twitter. This creates “a false illusion of extreme circumstances,” said David Stukus, a pediatric allergist at Nationwide Children’s Hospital in Columbus, Ohio, who joined Twitter in 2013 to fight misconceptions by disseminating evidence-based information. “People read a headline and now they think that their risk has changed.”

If there were a true balance of stories, Stukus said, for each tragic death that occurs and every story shared, “we would literally have a million other stories demonstrating that someone who has peanut allergy went to school that day, went to a ballpark, or flew on an airline without any problems at all.”

Still, food allergy sufferers can find themselves in dangerous situations if needed medication isn’t available. Since last year, EpiPens have been in short supply and are not always carried by airlines — something advocates are now pushing to change.

With rising pharmaceutical interest in developing food allergy products — two of which are heading toward an FDA decision — Kim worries that a single catastrophe with off-label OIT could set back the field.

The number of providers in the United States who currently offer off-label oral immunotherapy is estimated to be around 2 percent of board-certified allergists. It’s not easy for clinics to offer a highly individualized treatment that requires considerable time, clinical space, and nursing support, Schroer said. An even bigger obstacle, he noted, is the need to produce food-based products “to essentially pharmaceutical-grade levels.” Most allergists are waiting for an FDA-approved food allergy treatment before offering the therapy in their clinics. And in the case of peanut OIT, years ago leading experts believed that securing FDA approval would require measuring peanut flour into standardized capsules so each holds precise amounts of peanut protein. Aimmune Therapeutics launched in 2011 with that mission.

“The allergists who offered OIT early on were the pioneers, who had to blaze their own trails. Aimmune is working to lay the railroad and make the journey much easier and more reliable for everyone involved,” said Alison Marquiss, a former spokesperson for the Bay Area company.

Last November the New England Journal of Medicine published results of a clinical trial of AR101, Aimmune’s investigational peanut-containing drug. According to a company press release, it is the largest phase 3 peanut allergy oral immunotherapy trial to date, with 551 participants at 66 sites in North America and Europe. (Outside of research, private practice allergists in the United States have treated more than 7,800 patients with commercial food products.)

At the end of the Aimmune study, about two-thirds of the treated group were able to tolerate peanut protein equivalent to a dose of about two peanuts. Based on those results, the company submitted a licensing application. The FDA has said it will review the application in September and make a decision by January 2020. France-based DBV Technologies is developing a different type of immunotherapy called Viaskin Peanut, which delivers peanut proteins through a skin patch, and is headed for FDA review.

Outside of clinical trials, OIT has generally only been offered by private practice allergists. But as more data have come out, academic centers have begun to explore the possibility of offering the therapy as a service to patients. Some are already doing so.

“Especially as a public institution, we have the responsibility to translate what we’ve learned from trials to best practices,” said allergist Rita Kachru of the University of California, Los Angeles, which has served as a site for DBV and Aimmune trials.

Her team still considers the treatment investigational. “We are just starting to understand the risks, the benefits, the efficacy,” Kachru said.

“If we’re writing a novel,” she added, “we’re maybe at chapter 2. But I think we’re getting a better understanding, definitely more than a few years ago.”

At any given moment, OIT conversation on Food Allergy Treatment Talk, the Facebook group Sturner started, might highlight successes, discuss challenges, or raise questions. “It’s complicated. Because the human immune system is complicated. So are our emotions,” wrote Sturner on a Friday in March when a discussion about the risks and benefits of OIT became heated. “Read the threads. Absorb the info. Do your research. Most importantly, don’t panic.”

Esther Landhuis is a California-based science journalist who writes about biomedicine and STEM diversity. Her stories have appeared in Scientific American, NPR, Nature, Quanta, and Science News for Students, among other publications.

This article was originally published on Undark. Read the original article.