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Who are the potential patients for omalizumab for food allergy?

2024; Elsevier BV; Volume: 132; Issue: 5 Linguagem: Inglês

10.1016/j.anai.2024.03.006

1534-4436

Hugh A. Sampson, J. Andrew Bird, David M. Fleischer, Wayne G. Shreffler, Jonathan M. Spergel,

Asthma and respiratory diseases

Food allergies affect an estimated 8% of the US population and have risen significantly in the past 20 years.1Warren CM Aktas ON Manalo LJ Bartell TR Gupta RS. The epidemiology of multifood allergy in the United States: a population-based study.Ann Allergy Asthma Immunol. 2023; 130 (637-648.e5)Abstract Full Text Full Text PDF Scopus (13) Google Scholar IgE–mediated reactions to food can range from simple urticaria to life-threatening anaphylaxis. The only treatment was the avoidance of the allergen and treatment of allergic reactions with epinephrine until 2020 when an oral immunotherapy (OIT) product (Palforzia [Stallergenes Greer, Boston, Massachusetts]) was approved for the treatment of peanut allergy.2Vickery BP Vereda A Casale TB Beyer K du Toit G Hourihane JO et al.PALISADE Group of Clinical InvestigatorsAR101 Oral Immunotherapy for Peanut Allergy.N Engl J Med. 2018; 379: 1991-2001Crossref PubMed Scopus (470) Google Scholar There was no approved treatment by the US Food and Drug Administration for other foods or multiple foods until the recent approval of omalizumab for any food allergy for patients aged 1 year or older with the appropriate total IgE and weight. In the pivotal trial, Wood et al3Wood RA Togias A Sicherer SH Shreffler WG Kim EH Jones SM et al.Omalizumab for the treatment of multiple food allergies.N Engl J Med. 2024; 390: 889-899Crossref PubMed Scopus (8) Google Scholar reported in a randomized, placebo-controlled study that 67% of patients on omalizumab tolerated a single dose of 600 mg (1044 mg cumulative dose) or greater of peanut protein after 16 to 20 weeks of therapy. To be eligible for randomization, patients had to react in a double-blind, placebo-controlled challenge to a single dose of 100 mg (144 mg cumulative dose) or less of peanut protein and 300 mg or less of 2 other foods (milk, wheat, cashew, walnut, hazelnut, or egg). After therapy, the range of tolerating other foods at 1000 mg (1444 mg cumulative dose) was from 42% to cashew and 75% to wheat. There was a 30- to 400-fold increase in the median tolerated dose for each food compared with the baseline reactive dose (Table 1). However, it is important to remember the following when trying to expand these findings to all patients: (1) there were only 3 adult patients (2 on omalizumab); (2) some patients had a lower threshold dose after the 6-month open-label extension compared with the posttreatment challenge; and (3) there was high screen failure rate in the study (for example, too high total IgE level to qualify for omalizumab or not sensitive enough on food challenges).Table 1Response Rate to OmalizumabFoodTolerating 600 mgTolerating 1000 mgFold increase for tolerated dose from baseline to end of studyOmalizumab, %Placebo, %Omalizumab, %Placebo, %OmalizumabPlaceboPeanut676.7681.7100 ×0 ×Milk729.5669.5137 ×3 ×Egg760670432 ×0 ×Cashew503.2413.732 ×0 ×Hazelnut67176714449 ×0 ×Walnut75166416137 ×2 ×Wheat8213731342 ×3 ×Adapted from Wood et al.3Wood RA Togias A Sicherer SH Shreffler WG Kim EH Jones SM et al.Omalizumab for the treatment of multiple food allergies.N Engl J Med. 2024; 390: 889-899Crossref PubMed Scopus (8) Google Scholar Open table in a new tab Adapted from Wood et al.3Wood RA Togias A Sicherer SH Shreffler WG Kim EH Jones SM et al.Omalizumab for the treatment of multiple food allergies.N Engl J Med. 2024; 390: 889-899Crossref PubMed Scopus (8) Google Scholar Identifying the correct patient for the use of omalizumab will require a shared decision model among physician, patients, and their families.4Anagnostou A. Shared decision-making in food allergy: navigating an exciting era.Ann Allergy Asthma Immunol. 2024; 132: 313-320Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar The potential benefit of omalizumab of reduced rates of reaction on the basis of the surrogate marker of oral food challenges (OFCs) must be weighed against the adverse effects of omalizumab (likely small) and use of 1 or more injections 1 to 2 times a month. The benefit needs to be compared with other therapies including OIT and avoidance. Some potential patients in which the benefit of prescribing omalizumab may be high include the following: (1) high-risk patients, (2) patients anticipating a high-risk area/situation, (3) very anxious patients or their caregivers, and (4) potential bridge to OIT. The high-risk patient can have multiple components including increased risk for fatalities, such as asthma; adolescence; or allergy to milk, peanut, and/or tree nuts.5Pouessel G Turner PJ Worm M Cardona V Deschildre A Beaudouin E et al.Food-induced fatal anaphylaxis: from epidemiological data to general prevention strategies.Clin Exp Allergy. 2018; 48: 1584-1593Crossref PubMed Scopus (111) Google Scholar Another example of a high-risk individual is a patient who reacts to a low dose of food and who would be more likely to react at low levels of cross-contamination. An individual that has a multifood allergy (ie, peanut, several tree nuts, milk, egg, and wheat) or has multiple reactions despite best efforts of avoidance are additional examples, as is an individual who has had previous severe reactions leading to hospitalization or intensive care admissions. The final example is an individual with an underlying disease that places them at a high risk for a severe reaction or fatality such as a patient with prolonged QT syndrome. The patient traveling to a high-risk situation or area presents another group of patients who would benefit from omalizumab. Potential examples include traveling to locations in which food labeling is not clear, access to emergency medical care is potentially compromised (eg, camping), or the allergen is a main part of the diet, such as sesame in the Middle East. The optimal period of treatment needed before travel is unclear. The third category in which omalizumab might be helpful is the very anxious patient who has a poor quality of life, limiting social interactions because of fear of having an allergic reaction. Omalizumab might give them a level of comfort with the knowledge that there may be a potentially higher threshold for a reaction. However, these patients would still need to know the following: (1) that the success rate of omalizumab increasing the threshold ranged from 44% to 67%; (2) that the threshold is not always stable and may be affected by cofactors such as illness, exercise, sleep deprivation, nonsteroidal anti-inflammatory drugs medications or alcohol intake; and (3) that they would still need to avoid their allergens and carry a self-administered epinephrine device. In addition, there are probably better methods (eg, cognitive behavioral therapy) to treat food-induced anxiety than lifelong treatment with omalizumab.6Dahlsgaard KK Lewis MO Spergel JM. Cognitive-behavioral intervention for anxiety associated with food allergy in a clinical sample of children: feasibility, acceptability, and proof-of-concept in children.Ann Allergy Asthma Immunol. 2023; 130: 100-105Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar The final category is the use of omalizumab as a bridge to OIT, an off-label use of the medication for the individual who experienced frequent reactions or reacted at a very low dose during OIT. In the study by Andorf et al,7Andorf S Purington N Block WM Long A Tupa D Brittain E et al.Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial.Lancet Gastroenterol Hepatol. 2018; 3: 85-94Abstract Full Text Full Text PDF PubMed Google Scholar they found that 83% of individuals treated with omalizumab + OIT tolerated a 2-g OFC compared with 33% of those treated with placebo + OIT and experienced fewer adverse events associated with OIT doses (27% vs 68%). In a subsequent study, patients were able to wean off omalizumab after 16 weeks with a high rate (85%) of desensitization.8Andorf S Purington N Kumar D Long A O'Laughlin KLO Sicherer S et al.A Phase 2 randomized controlled multisite study using omalizumab-facilitated rapid desensitization to test continued vs discontinued dosing in multifood allergic individuals.EClinicalMedicine. 2019; 7: 27-38Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar However in other studies, up to 30% of patients had anaphylaxis when omalizumab was stopped.9Ayats-Vidal R Riera-Rubio S Valdesoiro-Navarrete L García-González M Larramona-Carrera H Cruz OA et al.Long-term outcome of omalizumab-assisted desensitisation to cow's milk and eggs in patients refractory to conventional oral immunotherapy: real-life study.Allergol Immunopathol (Madr). 2022; 50: 1-7Crossref PubMed Scopus (11) Google Scholar Patients need to understand that omalizumab is not disease-modifying and would need to be continued lifelong, except as a bridge to OIT to sustain protection. Recent studies suggested that allergen-specific therapies (eg, OIT,10Soller L Abrams EM Carr S Kapur S Rex GA Leo S et al.First real-world effectiveness analysis of preschool peanut oral immunotherapy.J Allergy Clin Immunol Pract. 2021; 9: 1349-1356.e1Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar epicutaneous immunotherapy,11Greenhawt M Sindher SB Wang J O'Sullivan M du Toit G Kim EH et al.Phase 3 trial of epicutaneous immunotherapy in toddlers with peanut allergy.N Engl J Med. 2023; 388: 1755-1766Crossref PubMed Scopus (35) Google Scholar or sublingual immunotherapy12Kim EH Bird JA Keet CA Virkud YV Herlihy L Ye P et al.Desensitization and remission after peanut sublingual immunotherapy in 1- to 4-year-old peanut-allergic children: a randomized, placebo-controlled trial.J Allergy Clin Immunol. 2024; 153: 173-181.e10Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar in young children) might be disease-modifying and need to be considered in shared decision-making. With any therapy, it is important to monitor effectiveness given that omalizumab was effective in increasing the threshold of reactivity to peanut in 67% of patients with allergy to a single dose of 600 mg (1044 mg cumulative dose) and various tree nut in 42% to 75% of other foods studied to a dose of 1000 mg (cumulative dose of 2044 mg).3Wood RA Togias A Sicherer SH Shreffler WG Kim EH Jones SM et al.Omalizumab for the treatment of multiple food allergies.N Engl J Med. 2024; 390: 889-899Crossref PubMed Scopus (8) Google Scholar At these levels, the responders should be protected against cross-contamination for most foods but not all.13Miller TA Koppelman SJ Bird JA Hernandez-Trujillo V Thyagarajan A Mack D et al.Peanut cross-contamination in randomly selected baked goods.Ann Allergy Asthma Immunol. 2022; 128: 439-442Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar However, it should be noted that omalizumab is indicated for use in conjunction with ongoing avoidance of the offending foods, and patients will still need to carry a self-administered epinephrine device to treat unanticipated allergic reactions secondary allergen exposures. It is critical that we determine whether the patients are responding to therapy as 33% to 58% will still react at the end points designed in the study. Our standard methods of skin testing and specific IgE quantification cannot reliably be used to determine whether natural tolerance has developed or whether the patient has responded to treatment because omalizumab alters test results, and currently available testing does not predict eliciting dose on OFCs. Therefore, we would recommend an OFC after 6 to 12 months of therapy to monitor response and give appropriate clinical guidance to patients and their families. It is unclear whether OFCs will need to be repeated because of the variability in response in the open-label extension.3Wood RA Togias A Sicherer SH Shreffler WG Kim EH Jones SM et al.Omalizumab for the treatment of multiple food allergies.N Engl J Med. 2024; 390: 889-899Crossref PubMed Scopus (8) Google Scholar Additional areas of research are needed to answer important clinical questions for patients. Can omalizumab be used in conjunction or bridge to other forms of immunotherapy such as OIT, epicutaneous immunotherapy, or sublingual immunotherapy? The ongoing Omalizumab as Monotherapy as Adjunct Therapy to Mulit-Allergen OIT in Food Allergic Children and Adults (OUTMACH) clinical trial may help answer some of these questions on the use of omalizumab in conjunction with or in comparison to OIT. In addition, what are the treatment options for patients with high total IgE levels that exceed the upper range of dosing for omalizumab? Will omalizumab still work in these patients, or do we need additional therapies such as other biologics or a combination of multiple biologics? It is hoped that these important questions will be answered by ongoing and future clinical trials and research, given that many patients will still need new or different therapies. Another issue to consider is the cost of omalizumab to patients and society compared with the cost of reduced emergency department visits and improved quality of life with fewer reactions. In conclusion, the approval of omalizumab is a major breakthrough in the treatment of food allergy and provides an important option for patients. However, shared decision-making will be required to decide whether to start therapy or not. More importantly, despite the potential benefits of omalizumab, patients and their families will still need to avoid the allergenic food, carry self-administered epinephrine, and possibly receive multiple monthly or 2-weekly injections. We think it will be an important therapy for some patients but not for all. Patients and their families will have to weigh the potential benefits of a higher reactive threshold vs the risks from avoidance or benefits from other therapies. It will be critical to explain to our patients the benefits and risks of this therapy so they can make an informed decision. Dr Bird reports receiving grants from the National Institutes of Health/ National Institute of Allergy and Infectious Diseases (NIH/NIAID); grants and personal fees from Genentech; grants and personal fees from Novartis during the conduct of the study; grants from Aimmune, Astellas, Regeneron, and Siolta; grants and personal fees from DBV Technologies and Food Allergy Research and Education (FARE); personal fees from Allergenis, Allergy Therapeutics, HAL Allergy, and Nutricia; and other fees from the American Academy of Allergy, Asthma, and Immunology, the American Academy of Pediatrics, the International FPIES Association, and Vedanta outside the submitted work. Dr Fleischer has received research support from ARS Pharmaceuticals and DBV Technologies; serves as an unpaid advisory board member for Food Allergy and Anaphylaxis Connection Team and the National Peanut Board; receives royalties from UpToDate; and received personal fees as a consultant to Aquestive, ARS Pharmaceuticals, Bryn Pharma, DBV Technologies, Genentech, and Nasus outside of the submitted work. Dr Shreffler reports receiving grants from NIH/NIAID; has contract research support from Genentech, DBV, Allergy Therapeutics, Aravax, and Novartis; and received personal fees from Aimmune, DBV, Novartis, ALK, Allergy Therapeutics, FARE, and UpToDate. Dr Sampson reports receiving grants to his institution from NIH/NIAID; has received consulting fees from DBV Technologies, S.A., N-Fold Therapeutics, LLC, and Siolta, Inc; and has stock options from DBV Technologies and N-Fold Therapeutics. Dr Spergel reports receiving grants from NIH/NIAID and Novartis during the conduct of the study and received grants and personal fees from Regeneron and Sanofi; personal fees from ACAAI, Syneos, UpToDate, and Readysetfood; and grants from Allakos outside the submitted work. The authors have no funding sources to report.