Sayantani Sindher, MD, is a clinical associate professor at the Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine.

Sayantani Sindher, MD

Dupilumab Improves Desensitization Outcomes in OIT, With Sayantani Sindher, MD

2026 American Academy of Allergy, Asthma & Immunology (AAAAI)

 annual meeting in Philadelphia, found that adding dupilumab to omalizumab-facilitated 

improved desensitization outcomes and reduced gastrointestinal adverse events.

However, it did not significantly increase sustained unresponsiveness. This begs the question: How should clinicians counsel patients about expectations for desensitization versus sustained responsiveness?

“I'm always trying to figure out how to apply sustained unresponsiveness data to the patient sitting in front of me,” investigator Sayantani Sindher, MD, clinical associate professor of medicine at Stanford University, told 

during the meeting. “When you have a patient in front of you as an individual, it's really hard to [figure] out, ‘Okay, are you going to be someone who will achieve sustained unresponsiveness versus not? ‘ In my outpatient care, I don't take them off of [therapy for] a long period of time. If they do miss many days or months of treatment, I will bring them back in and do observed dosing to get them right back on track. Until we have biomarkers available that can predict sustained unresponsiveness, it is not something I'm able to readily apply in my outpatient clinical care practice.”

The randomized COMBINE trial enrolled 108 individuals with multiple food allergies (peanut plus 1 or 2 additional allergens) and investigated whether dupilumab could improve outcomes during omalizumab-assisted OIT. Participants first received omalizumab for 8 weeks, after which they received OIT with either dupilumab or placebo from weeks 8 through 32. All therapies were discontinued at week 32, and sustained unresponsiveness was evaluated at week 44 using double-blind, placebo-controlled food challenges.

Although the trial’s primary endpoint, sustained unresponsiveness to ≥1043 mg of peanut protein, was not statistically different between groups, results suggested potential benefits with dupilumab. Sustained unresponsiveness was achieved in 39% of patients receiving omalizumab plus OIT and 55% of those receiving dupilumab plus OIT (

Secondary findings showed improvements in desensitization and tolerability with the addition of dupilumab. By week 32, 92% of patients receiving dupilumab tolerated the highest tested allergen dose (4043 mg) during food challenge compared with 63% of those receiving OIT without dupilumab (adjusted 

 =.013). Investigators also reported fewer gastrointestinal symptoms and treatment withdrawals in the dupilumab group.

Despite encouraging signals, Sindher emphasized that translating combination biologic strategies into routine practice requires consideration of real-world factors such as insurance coverage and drug costs.

“In clinical trials, we have funding to obtain the drugs. In the outpatient world, it all goes through insurance, and access is a big deal,” Sindher said. “The cost of it is… something we have to think through before… we start using it.”

Future analyses of the COMBINE trial are exploring immune mechanisms underlying treatment responses, including assessments of B cells, T cells, and basophil activation. Sindher said these efforts may help identify patient subgroups most likely to benefit from combination biologic approaches and inform more personalized strategies for managing food allergy.

“What we need is a much better understanding of why it works,” Sindher said. “Who is the population it works best for, and also who is the population it doesn't work for? Once we have better predictive biomarkers or algorithms that help us phenotypically cluster these patients, it'll be really hard to know when to use these biologics…Many of our food allergic kids and adults also have many other atopic conditions [such as asthma, eczema, seasonal allergies, eosinophilic esophagitis] …Having different biologics approved for some of these indications that may also help for food allergy would really help us address multiple atopic conditions with just one drug.”

A relevant disclosure for Sindher includes Genentech USA.

Sindher S, Long A, Garcia-llorett M, et al. The addition of dupilumab enhances desensitization and reduces gastrointestinal symptoms in omalizumab-facilitated multi-allergen oral immunotherapy in the COMBINE trial. 

Journal of Allergy and Clinical Immunology

doi:https://doi.org/10.1016/j.jaci.2025.12.917

Sindher S. Dupilumab Reduces GI Symptoms During Multi-Allergen OIT, With Sayantani Sindher, MD. HCPLive. Accessed on March 12, 2026. Published on March 5, 2026. 

https://www.hcplive.com/view/dupilumab-reduces-gi-symptoms-multi-allergen-oit-sayantani-sindher-md

Videos

Data presented at AAAAI 2026 showed that adding dupilumab to omalizumab-facilitated oral immunotherapy improved desensitization and reduced gastrointestinal adverse events.

HCPLive Five: AAAAI 2026

 annual meeting in Philadelphia from February 27 – March 2, investigators presented new data spanning drug hypersensitivity, food 

 treatment, microbiome science, and biologic therapies for chronic inflammatory disease.

In this installment of HCPLive Five, the editorial team highlights 5 key expert interviews conducted on site, featuring insights from leading clinicians and investigators on emerging data. Topics include pharmacogenomic risk for lamotrigine-induced DRESS, adjunct biologic strategies for multi-allergen oral immunotherapy (OIT), microbiome modulation in infants born via cesarean delivery, and long-acting biologic therapies for chronic rhinosinusitis with nasal polyps (CRSwNP) and hereditary angioedema (HAE).

HLA-A*32:01 Linked to Lamotrigine DRESS Risk, With Matthew Krantz, MD

New research highlights a strong genetic association between the antiseizure medication lamotrigine and drug reaction with eosinophilia and systemic symptoms (Drug Reaction with Eosinophilia and Systemic Symptoms) among carriers of the HLA-A*32:01 allele. In an interview, Matthew Krantz, MD, of Vanderbilt University Medical Center, discussed prospective case-control findings conducted with Mass General Brigham showing 12-fold increased odds of lamotrigine-induced DRESS among HLA-A*32:01 carriers.

The multi-institutional analysis included 30 confirmed DRESS cases and 300 lamotrigine-tolerant controls from the BioVU biobank. Findings show the potential role of HLA genotyping in clarifying causality when multiple medications are involved and may inform future pharmacogenomic strategies to identify patients at elevated risk for severe lamotrigine hypersensitivity.

Dupilumab Reduces GI Symptoms During Multi-Allergen OIT, With Sayantani Sindher, MD

Findings from the COMBINE trial suggest the biologic dupilumab may improve tolerability and desensitization during omalizumab-facilitated multi-allergen OIT. In an interview, Sayantani Sindher, MD, from Stanford University, discussed results from the randomized study of 108 patients with multiple food allergies undergoing OIT. Although adding dupilumab did not significantly improve sustained unresponsiveness, it increased tolerance to higher allergen doses and reduced gastrointestinal adverse events.

Participants receiving dupilumab tolerated larger allergen exposures and experienced fewer GI symptoms per dose. Findings suggest dupilumab may serve as a targeted adjunct therapy to improve safety and patient experience during multi-allergen OIT.

Vaginal Seeding Partially Modifies Infant Microbiome in ACTIVATE, With Jose Clemente, PhD

Results from the ACTIVATE trial suggest vaginal microbial transfer may partially modify the infant gut microbiome in cesarean-delivered infants and influence early allergy risk. In an interview, Jose Clemente, PhD, from Icahn School of Medicine at Mount Sina, discussed findings showing that vaginal seeding increased colonization with beneficial microbes such as 

 shortly after birth and temporarily shifted microbiome profiles toward those seen in vaginally delivered infants. Although global microbiome differences diminished by 12 months, infants with successful microbial transfer showed lower levels of microbes associated with food sensitization.

Twice-Yearly Depemokimab Reduces Rescue Use in Recurrent CRSwNP, With Josesph Han, MD

A pooled post hoc analysis of ANCHOR-1 and ANCHOR-2 suggests the anti–IL-5 biologic depemokimab may improve disease control in patients with CRSwNP and prior surgery. In an interview, Joseph K. Han, MD, from Old Dominion University, discussed findings showing twice-yearly depemokimab improved nasal obstruction, sense of smell, and health-related quality of life compared with placebo in patients with type 2 inflammation. Depemokimab significantly reduced the need for rescue interventions such as systemic corticosteroids or additional surgery.

Navenibart at 3- and 6-Month Dosing Reduces HAE Attacks, With Adil Adatia, MD

Interim phase 2 ALPHA-SOLAR data suggest the investigational monoclonal antibody navenibart may provide durable prophylaxis for HAE types 1 and 2. In an interview, Adil Adatia, MD, from University of Alberta, reported that both 3-month and 6-month subcutaneous dosing schedules produced substantial reductions in HAE attacks, with median reductions exceeding 95%. The long-acting plasma kallikrein–targeting antibody demonstrated a favorable safety profile, with mostly mild treatment-emergent adverse events and few injection-site reactions.

Investigators also noted improvements in patient quality of life as attack frequency declined. Findings support continued evaluation of navenibart in the ongoing phase 3 ALPHA-ORBIT trial.

This HCPLive Five captures 5 interviews conducted on-site at AAAAI 2026.

HCPLive Five at AAAAI 2026

American Academy of Allergy, Asthma & Immunology (AAAAI) 

Annual Meeting in Philadelphia suggest that adding dupilumab to omalizumab-facilitated 

may improve desensitization outcomes and reduce gastrointestinal adverse events, though it did not significantly increase sustained unresponsiveness.

The findings come from the COMBINE trial, which evaluated whether adjunct dupilumab could enhance outcomes in patients undergoing multi-allergen OIT supported by omalizumab. In an interview with

during the meeting, Sayantani Sindher, MD, clinical associate professor of medicine at Stanford University, explained that the study was designed in part to address a persistent clinical challenge in OIT: gastrointestinal symptoms and treatment-related adverse events that can limit patient adherence and long-term success.

“We were hoping that with the study, we [would] get a better insight into the participants who are developing GI symptoms and whether we can do something about it for this subgroup of patients and improve long-term positive treatment outcomes,” Sindher said.

The randomized trial enrolled 108 individuals with multiple food allergies, including peanut plus 1 or 2 additional allergens. Participants were assigned to receive omalizumab followed by placebo plus OIT, omalizumab followed by dupilumab plus OIT, or a smaller mechanistic arm. Omalizumab was administered during the first 8 weeks, followed by dupilumab or placebo with OIT from weeks 8 through 32. All therapies were discontinued at week 32, and sustained unresponsiveness was assessed at week 44 using double-blind, placebo-controlled food challenges.

The primary endpoint, sustained unresponsiveness to ≥ 1043 mg of peanut protein, was achieved in 39% of patients receiving omalizumab plus OIT and 55% of those receiving dupilumab plus OIT, a difference that did not reach statistical significance (

 = .16). Sindher noted that sample size likely contributed to the lack of statistical significance despite a numerical difference between the groups.

Although the primary endpoint was not met, secondary analyses showed meaningful differences in desensitization and tolerability. At week 32, a significantly greater proportion of patients receiving dupilumab tolerated the highest tested cumulative dose of a single allergen (4043 mg) during food challenge compared with those receiving OIT alone (92% vs 63%; adjusted 

Sindher emphasized that the ability to tolerate approximately 4 grams of allergen protein, roughly equivalent to a full serving size of food, can be clinically meaningful for many patients and families.

“In terms of clinical meaningfulness…this is where shared decision making comes through,” Sindher said. “For some of our patients, they're like, ‘That's great, but I never want to eat the food again. I just want to do the bare minimum so I can sustain my effectiveness,’ in which case we would say, ‘okay, sure, you can absolutely do lower doses of OIT, but you just know that you're protected against much higher doses in case of accidental exposure.’ And then in our younger group, who may [be] too young to even understand food allergy and don't have the fear of the food yet, it gives parents an opportunity to actually introduce full serving size amounts of the foods of their allergens and incorporate it as part of their diet.”

Safety findings also highlighted potential advantages of adding dupilumab. Withdrawals due to adverse events, most commonly gastrointestinal symptoms, occurred only in the omalizumab-plus-OIT arm (n = 8;

 = .006). Additionally, gastrointestinal symptoms per OIT dose were significantly lower in the dupilumab group (0.013 vs 0.033;

“What was also interesting, and I see this in my outpatient clinical care practice, and we see this in this study, is as helpful as dupilumab [is]… the effects are not long lasting, so the kids revert back to the state they would have been with just multi-OIT by itself,” Sindher said. “What this means is that dupiumab may be a great addition to the toolkit for our treatment options for our patients, depending on what their side effects are, and just allow us to do more precision medicine, but to do that more we need a better understanding of the underlying mechanisms and identify better biomarkers that can predict different profiles of kids, and that will allow us to pick the right tool for the kid that we have in front of us.”

COMBINE trial data show dupilumab added to omalizumab-assisted OIT improved desensitization and reduced GI symptoms, despite no sustained response benefit.


Edwin H. Kim, MD

Michelle Huffaker, MD

 is a phenomenon that touches the lives of almost everyone in some way, whether one is a patient or has a relationship with a patient.

Allergies to food are a significant concern, given the potential for anaphylaxis among those with Type 1 hypersensitivities. In fact, close to 200,000 individuals require emergency medical care for allergic reactions to food allergens and more than 50% of the 33 million adults in the US with food allergies report experiencing severe reactions.

Parents had become concerned over the years about their children reacting to food allergies, so protocols for avoidance of allergens became the norm by the outset of the 21st century. The 2000 recommendations by the American Academy of Pediatrics (AAP) urged avoidance of major allergens such as peanuts, milk, and eggs.

Allergies to these food products appeared to rise among children in the US between 2000 - 2009.

 It was only recently that the allergy research space made a dramatic shift away from avoidance and toward early exposure and immunotherapy, resulting in the landmark 

US Food and Drug Administration (FDA) approval

 in 2020 of AR101 (Palforzia) as the first food allergy-related immunotherapy.

Since 2020, this dramatic shift in the field of food allergy research has given way to a variety of advancements. 2024 represented another major leap forward, with 2 significant FDA approvals: 

Omalizumab was the first treatment designed to prevent anaphylaxis resulting from exposure to 1 or more food allergens in adults and childrens aged 1 year and older with immunoglobulin E (IgE)-mediated food allergies. Epinephrine nasal spray, also known as ‘neffy,’ is the first alternative option to injectable epinephrine (in such products as the EpiPen).

 editorial team reached out to 3 experts in the field of allergy research to discuss these notable advancements, their significance as ‘firsts’ in the allergy space, and what they mean for patients now that they have been approved.

The team spoke with Edwin H. Kim, MD, associate professor of pediatrics at the University of North Carolina’s School of Medicine. We also spoke with Sayantani Sindher, MD, a clinical associate professor of allergy and immunology at Stanford Medicine. Our third expert was Michelle Huffaker, MD, the director of clinical translational medicine in the Allergy Portfolio at the Immune Tolerance Network.

Each of these speakers are leading experts in the field of allergy and immunology. Below are several notable quotes from 3 interviews on the topic of the aforementioned developments in the allergy space in 2024.

On Evolving Allergy Research and New Developments:

 I would absolutely agree that this has been the biggest year I could think of when it comes to food allergy therapeutics and treatment options. Really thinking back over many years, it's really just been about diagnosing the allergy and giving guidance and avoidance. Several years ago, we had the approval of peanut oral immunotherapy as well as clinical use of food products for this type of thing.

But these were very sort of narrow types of treatments that were only available through specialized clinics. So omalizumab being approved by the FDA is a dramatic change when it comes to food allergy. One of the biggest reasons, in my mind, is because pretty much every allergy office in the United States at this point is likely offering omalizumab for asthma or for hives and urticaria. So now to be able to offer that same medication that they have so much experience with for food allergy, inevitably, is going to increase access.

 It felt like a very momentous year for food allergy, with omalizumab, with neffy, and in fact with another product, Palforzia. The age range went down even lower, as it was previously 4 and up and now it's been shifted to 1 year olds and up. That's extending the age group for when we can offer therapies.

I think having all these treatment options early on changes the mindset when we think of allergy care, instead of what we used to do forever where we diagnose and we say ‘Okay great, now you just avoid it, hope for the best, and we'll see what comes around down the line.’ Whereas now, when I'm diagnosing a 5-month-old or 6-month-old, I can provide them with ‘You know, when you turn 1, you have these options.’ There are these other treatment options in the pipeline and there's just a lot more opportunities for patients to decide what's the right track for them.

The patients are very grateful to have options now. For years, it was avoidance and epinephrine auto injectors. And now they are very grateful that the field is moving forward and that there are more treatment options available, even if they don't just choose to elect those treatment options at this time. There are a variety of reasons that they might choose not to, but just having choices and options has really changed things for those patients.

On Omalizumab and Its Impact on Patients:

I think the earliest patients are on the therapy at this point. So it will take a little bit of time to really get an assessment of how this truly affects those patients. We know what to expect from the clinical trials, but real life is not always the same. I do want to bring up the point that I started with previously, that it increases access and one of the biggest things that it does is (function as) a treatment that can be given for any and all food allergies.

So it really can potentially address food allergies for almost every patient that's out there. The prior treatments, the oral immunotherapy, really could not. It will be really interesting to see the effect that this treatment has on patients, as well as whether there are ‘ideal patients’ for this or patients with certain food allergies do better than those with other food allergies. (There are) lots of these types of questions, so we can fine tune how we use this in the clinic.

I still remember when it got approved. I was away internationally, and I started getting texts from all my colleagues, along with emails. Patients were reaching out when the FDA first approved it, so my colleagues and I have been very excited about this development…One of the reasons I'm super excited is that it gives patients and families choices, because that's one of the things I am hoping for, with more and more advancements coming through…It is great for anyone who doesn't want the hassle of daily oral immunotherapy, which we can address later.

This has been a very exciting year for the world of food allergy and for patients and families dealing with food allergies. And one word you said there really hits on how omalizumab changes the landscape, and that's that's the word ‘options.’ Traditionally, food allergies have been managed completely with avoidance and managing reactions with epinephrine.

It can be frightening for patients. It can be frightening for families. It can be very challenging to avoid all the food allergens and what omalizumab does is it's an extra safety net against those accidental exposures. So decreases the likelihood that anaphylaxis will occur if you were to have an accidental exposure. And so it really opens up options for patients, it potentially liberalizes their diet. It also really changes the level of anxiety that there may be around food allergy.

On the Impact of Epinephrine Nasal Spray:

 I think this has the potential to have a dramatic effect, because every patient out there who has food allergy should have an epinephrine auto-injector to be used as treatment if they were to have an allergic reaction. So a change to that has the potential to affect pretty much every patient that's out there. We know that this is separate from the treatments, because the treatments are there to prevent allergic reactions, but when allergic reactions happen, we know that epinephrine is the best medicine.

That first line medicine that will treat all the symptoms and ideally prevent symptoms from becoming more significant or more severe. At the same time, what we have understood anecdotally, but also now more from actual data on usage, is that a lot of folks that could and should be using that epinephrine auto-injector just haven't been for a multitude of reasons. One of the biggest ones being the injection route itself. So now to have a medication that I hope people are going to be more willing to use, it'll be fantastic to see what kind of effect this will have from the usage of the medication and, hopefully, prevent more significant allergic reactions.

 I think a lot of our adolescent patients are very excited. They love the idea of just being able to spray in their nose and not the injection. We've had so many. We do a lot in our research unit and we do a lot of food challenges. As part of participation in a clinical trial, we have to show that you are truly allergic to a food, and the gold standard of diagnosis is giving them the food that they're allergic to and waiting for a reaction and then treating that reaction.

So we see kids and adults just more terrified about the injection than about the reaction itself. We've had patients who have sat through anaphylaxis on their own because they didn't want to inject themselves. There's also user error. Some parents may have injected themselves instead of the child in the process. So there's lots of kinds of barriers to getting optimal care when it comes to the injectables.

It is another exciting new option for patients in the world of food allergy. It's still kind of coming into the market, so we're still seeing how patients are adopting it. I think one thing that I'm hopeful about with it is that it will lower the bar for use of epinephrine. Giving yourself an injection often feels like a very big deal to patients, even though that really should be the first thing they turn to with systemic allergic reactions. Previously, we only had that through injection.

What I'm hoping is that patients that may be hesitant to give themselves an epinephrine injection would potentially give themselves a nasal spray of epinephrine, if the treatment is just as effective as the injectable form. As a clinician, I don't care which one gets into them, but I want one of them to get into them for patients having a reaction. So if the nasal spray can lower that bar for use, its has potential to save lives.

The quotes contained in this article were edited for the purposes of clarity. For further information, view the interviews posted above.

Kim has reported consulting fees from ALK-Abelló, Ukko Inc., Cellergy Pharma, DBV Technologies, Genentech, Hanimune Therapeutics, Novartis, Nutricia, Phyalxis BioScience, and Revolo Biotherapeutics; safety review committee membership with Allergy Therapeutics Ltd.; royalties from UpToDate; and has stock options for Cellergy Pharma.

Sindher has reported receiving research grant support from NIH, FARE, CoFAR, DBV, AIMMUNE, and Regeneron and has worked as an advisor for Genentech.

Facts and Statistics. Food Allergy Research & Education. https://www.foodallergy.org/resources/facts-and-statistics?gad_source=1&gclid=Cj0KCQiAm4WsBhCiARIsAEJIEzXD8KiNDPvqo8HvRtRBBTjbmyyWhktLJrOiNjLUEqTNRSyo_6_4Z3caAl0JEALw_wcB. Date accessed: December 16, 2024.

Committee on N. Hypoallergenic infant formulas. Pediatrics. (2000) 106(2):346–9. 10.1542/peds.106.2.346. Date accessed: December 16, 2024.

Branum AM, Lukacs SL. Food allergy among children in the United States. Pediatrics. (2009) 124(6):1549–55. 10.1542/peds.2009-1210. Date accessed: December 16, 2024.

FDA approves Xolair® (omalizumab) as first and only medicine for children and adults with one or more food allergies. Novartis. February 16, 2024. https://www.novartis.com/us-en/news/media-releases/fda-approves-xolair-omalizumab-first-and-only-medicine-children-and-adults-one-or-more-food-allergies#:~:text=EAST%20HANOVER%2C%20N.J.%2C%20Feb.,patients%20aged%201%20year%20and. Date accessed: December 16, 2024.

Office of the Commissioner. FDA approves first nasal spray for treatment of anaphylaxis. U.S. Food and Drug Administration. August 9, 2024. Accessed August 9, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-nasal-spray-treatment-anaphylaxis. Date accessed: December 16, 2024.

Kim, Sindher, Huffaker spoke with HCPLive about some of the year’s most important developments in the food allergy space, namely the approvals of omalizumab and neffy.

Sayantani Sindher, MD

Articles