Is OIT Ready for Private Practice? — Three Perspectives
By Christine Lin Patel
Oral immunotherapy (OIT) is currently being studied in clinical trials at the Sean N. Parker Center for Allergy and Asthma Research at Stanford University as a promising treatment to desensitize patients with food allergies to specific allergens. As the parent of a child with severe food allergies, I sought to better understand the current perspective of private practice allergists on OIT and other potential food allergy treatments. Three board-certified allergists in the San Francisco Bay Area, Dr. Joann Blessing-Moore, Dr. Anjuli Mehrotra, and Dr. Steven Rubinstein were kind enough to make time in their busy schedules to share their thoughts on the potential use of OIT for their food allergy patients, the use of Xolair (omalizumab) in conjunction with OIT, and other potential therapies in development for treatment of food allergies.
OIT is being studied in clinical trials as a way to desensitize patients with food allergies to specific allergens. It needs to be carefully administered in a controlled setting. Each physician shared their current thoughts on OIT.
Dr. Mehrotra: Most of my experience with OIT has been at Stanford, working as Adjunct Faculty with the food allergy team. In the past, the only options we could give patients with food allergy was avoidance of allergenic foods and the use of Epipen on accidental ingestion of allergens. But food allergen avoidance isn’t that simple. There is so much work that goes into meal planning with kids who have food allergies. Parents also constantly live with fear that their kids will accidental ingest allergenic foods, particularly when they go to a friend’s house or to school. Food allergies can really play a huge role in one’s quality of life.
I am excited and hopeful about the future of OIT. Our current understanding is that OIT seems to work well to control food allergy reactions in the short term. However, we need to determine if it produces long-term tolerance and a “cure” for food allergy. OIT provides a very viable treatment option to keep our patients from having reactions from cross-contamination and a better quality of life. One of the best things about OIT is that it gives families an option to be less fearful of cross-contaminations.
I would consider OIT in my private practice as I want to give my patients an option for treatment. However, there are still some questions and concerns regarding OIT that need to be addressed, such as side effects and long-term effectiveness. The process of desensitization can be cumbersome and can be difficult for families and providers. The logistics and the amount of time it takes to desensitize can be tough. Because OIT patients need a lot of individualized attention and time, it may be hard to incorporate this practice into private allergist’s offices.
The question of dosing for OIT has also come up. What is the optimal dosage to start with, end at, and what are the time intervals between doses? Is there a better way to administer the doses? It can be a challenge to make a child eat foods predictably every day of their life.
It is important to evaluate each potential therapy’s benefits and limitations and decide which choice is best for each patient. It’s also nice to also see some other types of novel options are being studied, such as patch immunotherapy, Chinese herbs, and others.
Dr. Blessing-Moore: OIT has potential and is being studied extensively, but we do not have one treatment protocol established for general use on a national basis as of this time. It is exciting that Dr. Kari Nadeau is conducting OIT research and is evaluating the optimal dose, interval, duration of treatment as well as assessing the protection that OIT provides. In our office, we do a lot of food testing and oral food challenges. We need these clinical studies in order to provide physicians adequate data and information concerning this treatment option for food allergic patients.
OIT has great potential for the right patient. We need to evaluate, test and follow patients closely for food allergies as well as for environmental allergies, and we need the academic support for some cases. I send complex patients to Dr. Nadeau for study inclusion. We expect to get a better understanding over time by looking at the results of well-established protocols. Studies need to be well controlled and graded. Based on data, we can develop parameters and help the community.
Dr. Rubinstein: I am on board with performing OIT, as it has been shown to be invariably effective if done correctly under close supervision. Currently this is only recommended through active FDA sanctioned studies. I am especially grateful for the studies being conducted at the Sean N. Parker Center for Allergy and Asthma Research.
To truly know if a patient is allergic, a graded in-office food challenge is necessary. The standard approach is to start with a tiny amount of the food allergen and increase this amount every 15-30 minutes over 3-4 hours until a reaction occurs or the patient has received a substantial amount of allergen. Many of the OIT protocols that are being studied take this approach, initially testing a patient's threshold until a reaction, and then setting doses from there. Another approach, which I have used, is to start out at tiny doses and stop the challenges after a small amount of that food is tolerated. This way we know that an accidental exposure is not likely to cause a severe reaction. Rather than risk a reaction at higher amounts, I have the patients continue that small amount and have the parents slowly build up at home over the next month or so. With my approach we don’t really know if the patient would react at higher amounts, but I have had excellent success.
All three physicians shared their concerns regarding the potential limitations of OIT.
Dr. Mehrotra: There are some limitations to consider regarding OIT. I’ve already eluded to some issues that I see with OIT, including the difficult process of desensitization. The process of taking a daily dose of foods can be hard, especially with children. Further, more long-term as well as large-scale studies of OIT are needed before widespread adoption of the treatment. We need to better understand how to optimize dose for OIT and also learn what modifications need to be made to current treatment protocols so that ultimately, long-term tolerance of food allergens can be brought about.
The possibility of eosinophilic esophagitis (EoE) is another risk. There are different types of allergic reactions that can occur, which may not be as obvious as the classic immediate reactions that we identify with food allergy. As the food passes through the esophagus, it may trigger cells to become inflamed in the esophagus. With EoE, patients could have a local reaction in the esophagus after eating foods that they are allergic to, which could cause delayed reactions. Recurrent vomiting or coughing are common symptoms for kids. Some adults with EoE may complain about food getting stuck while eating and, in severe cases, need to get a dilation of their esophagus for food to pass.
Dr. Rubinstein: It's important to note that these OIT protocols are still not officially sanctioned by the FDA, as they have not yet fully satisfied benchmarks of effectiveness and safety. There are also a number of practical limitations with OIT. Finding the staff to accurately measure each allergen and create a daily dose for all patients is potentially prohibitive. Since OIT is currently not the standard of care outside of clinical studies, an allergist conducting OIT out of his own office would be medically liable should any severe reactions occur. Overall, there is some controversy with allergists currently attempting OIT in their private offices.
Even once patients are desensitized, compliance will remain an issue as current protocols require that the individual consume a maintenance dose daily for an indefinite time. Currently, however, there’s no way to know whether they can eat these foods intermittently or whether they need to eat them daily indefinitely. Ongoing studies are trying to find answers to these question with the ultimate goal of finding ways to allow a patient to eat the formerly allergenic food whenever he or she wants. Continuing to eat these foods every day is frequently quite challenging – even for the most committed patients.
Dr. Blessing-Moore: With OIT, the staff needs to be well trained in the treatment of allergic/anaphylactic reactions. Reactions can occur during oral food challenge. Patients and families/caregivers need to know how to recognize symptoms and treat appropriately. Benadryl or other quick acting antihistamines are fine for a skin reaction but epinephrine is needed for breathing difficulties or generalized systemic reactions. Call 911 immediately if symptoms occur – DO NOT WAIT.
Xolair (omalizumab) is a drug used for treatment of asthma. It is currently being used in combination with OIT in clinical trials for food allergy. Dr. Rubinstein and Dr. Blessing-Moore both elaborated on the specific potential of this adjunct therapy with OIT.
Dr. Rubinstein: Some of the studies at Stanford use Xolair in conjunction with OIT. First off, it might be helpful to explain how Xolair works. IgE is an antibody that is found in large amounts in individuals with food allergy and these antibodies attach to certain cells containing molecules called histamine. When food allergens are consumed by these individuals, these allergens bind to the IgE and trigger release of histamine and other molecules, which immediately cause symptoms of allergy. Xolair binds IgE and prevents the food allergen from binding to it, decreasing the allergic reaction. The use of Xolair lessens the risk of an anaphylactic reaction and enables the physician to quickly increase the amounts of food allergens given during immunotherapy. In one of the studies currently being conducted at Stanford, individuals are simultaneously desensitized to as many as 5 allergens while on Xolair. This study requires a significant amount of labor as all the food allergens have to be measured for all the different doses used. Most food desensitization studies require up to 12-18 months to reach full doses; with the use of Xolair, this is reduced to 3-4 months. At the start of each study, patients need to come in to the hospital for a double blind food challenge — once for a challenge with each allergenic food and once for a challenge with a placebo. These challenges can determine the starting dose of each food allergen for immunotherapy. Once the desensitization program starts, the patient usually has to come every two weeks, generally spending at least two hours in the hospital. However, protocols for different studies can vary.
Dr. Blessing-Moore: I have used and studied Xolair for asthma and hives. In many cases, if patients also have food allergy, it can help control their food allergy symptoms. Xolair, however, is not FDA approved for treatment of food allergy. It is a drug approved for asthma and hives.
Dr. Mehrotra and Dr. Blessing-Moore weighed in on other potential therapies for food allergies that are currently being evaluated, such as epicutaneous immunotherapy (EPIT), sublingual immunotherapy (SLIT), encapsulated peanut powder, or CODIT™ (Aimmune Therapeutics), and the use of traditional Chinese medicine.
Dr. Mehrotra: EPIT using a patch seems to be a very exciting option. A patch is used to deliver increasing doses of food allergen through the skin. This treatment method is likely to have fewer side effects than OIT and may also be able to get an individual desensitized so that they no longer need to fear reactions due to ingestion of cross contaminated foods. EPIT is convenient as the patch can be easily and safely applied at home. The ease of use is really a huge benefit. The patch is still being studied, so we are not sure if this treatment is the answer, but the studies conducted so far have been promising. SLIT is another treatment being studied, but It is hard to comment on SLIT for food because it hasn’t been studied as much as other methods. The goal of Aimmune’s characterized oral desensitization immunotherapy, or CODIT, is limited to helping protect against reaction due to cross contamination, rather than complete desensitization to normal consumption levels of that food. Their goal is to not eat the food allergen freely, but rather, to avoid reactions to small doses such as those likely equivalent to that encountered due to cross-contamination. I am glad that something like this may be available for our patients on a non-research basis in the near future. Dr. Xiu-Min Li in New York is working with allergists at Mount Sinai, evaluating the treatment of allergies with Chinese medicine and non-traditional herbs. They have seen some really interesting results with what seems to be minimal side effects. I’m looking forward to seeing the results of their long-term studies. It is important to evaluate the benefits and limitations of each potential therapy and decide which choice can be best for a patient. We’re all excited about the possibility of having better therapies to offer our patients in the near future.
Dr. Blessing-Moore: There are many new and novel developments in food allergy research and it is a very exciting time. Currently, SLIT is FDA approved only for ragweed and grass, but is being studied for other allergens. One apparent drawback is that if you have too many antigens in one tablet the efficacy may not be adequate. We will learn more as these products are better studied.
There are also a number of new tests that are more specific and which can determine which individual proteins in specific foods people react to. If we can identify the protein, then we can learn how to more precisely evaluate and treat.
All three physicians expressed that it is an exciting time in allergy research. Patients and parents are encouraged to learn more about these emerging food allergy therapies and to contact the Center to be pre-screened to participate in a clinical trial.
About the Author
Christine Lin Patel received her MBA from the Stanford Graduate School of Business with a focus on healthcare. She has a 6-year-old son with severe food allergies and is committed to spreading awareness of allergies.