key: cord-1001654-wl9wmdqm
authors: Leef, Chelsea; Horton, Codi; Lee, Tricia; Lee, Gerald; Tison, Katherine; Vickery, Brian P.
title: Exploring Barriers to Commercial Peanut Oral Immunotherapy Treatment During COVID-19
date: 2021-11-09
journal: J Allergy Clin Immunol Pract
DOI: 10.1016/j.jaip.2021.08.044
sha: c1ec052958b6276834703f8da1f95e98606f8ae0
doc_id: 1001654
cord_uid: wl9wmdqm

nan

Clinical Implications: Expanding real-world access to peanut oral immunotherapy (OIT) through an FDA-21 approved approach may be primarily limited by challenges inherent to OIT including time commitment 22 and lifestyle modifications. 23 24 Key words: Oral immunotherapy, peanut allergy, food allergy treatment, desensitization 25 26 Conflict of Interest Statement: Dr. Vickery reports grants and personal fees from Aimmune, personal 27 fees from AllerGenis, personal fees from Aravax, grants from DBV, grants and personal fees from FARE, 28 grants from Genentech, grants from NIH-NIAID, personal fees from Reacta Biosciences, grants from 29 Regeneron, outside the submitted work. The remaining authors have no conflicts to disclose. Among children in the United States, the prevalence of peanut allergy has continued to rise and 41 contributes substantially to the mortality and morbidity of food allergies (1-3). While the standard of 42 care for peanut allergy is strict allergen avoidance in addition to early use of rescue medications, 43 accidental ingestions often occur, and can result in severe allergic reactions across the lifespan (4, 5) . 44 Despite significant patient and caregiver motivation to reduce the risk of these accidental reactions, 45 treatment options for peanut allergy have not been widely accessible until recently (6) . 46 47 On 31 January 2020, the first food allergy treatment, a biologic drug used in peanut oral 48 immunotherapy (Palforzia), was approved by the Food and Drug Administration (FDA) (7) . Palforzia 49 offers protection to peanut-allergic patients by producing desensitization and modulation of the 50 immune response to peanut protein (8) . , Additionally, the use of Palforzia has been associated with 51 improvement in patient-reported quality of life (8) . However, it is well recognized that Palforzia also 52 involves burdens common to OIT, including daily dosing and required lifestyle modifications. 53

This new therapy represents a paradigm shift in peanut allergy treatment because it is scalable, and 54 will create opportunities for more patients to access peanut OIT. Further research is needed to better 55 understand how this treatment translates into real-world clinical practice. Most studies about caregiver 56 knowledge, preferences, and expectations of treatment were conducted in highly selected populations 57 participating in clinical trials, or in community-based settings that use non-FDA-approved approaches to 58 OIT (9) . We performed a qualitative study to identify barriers to initiating Palforzia treatment perceived 59 by real-world patients and caregivers in our academic pediatric allergy clinic. 60

Prior to the anticipated FDA approval of Palforzia, we created a peanut OIT waitlist to capture all 61 families who expressed interest in therapy during a routine clinic visit. Following Palforzia's approval and contacted all 67 established patients on the waitlist from June 2020 to January 2021. An electronic 64

REDcap survey was sent to each guardian by email, and the guardian was provided the American College 65 of Allergy, Asthma and Immunology's shared decision-making (SDM) tool regarding Palforzia to review. 66

After reviewing this document, the guardian had the opportunity to decline therapy prior to being 67 contacted for a consult and document their reason for decline. The survey listed six reasons for decline, 68

including: potential cost, safety concerns, too many office visits, comfortable with avoidance and don't 69 see the benefit of treatment, already receiving peanut OIT elsewhere, or my child is allergic to multiple 70 foods, along with an "other" option and a free text box available to outline the rationale for decline. All 71 remaining families were then contacted to schedule an hour-long in-person consultation visit to discuss 72 benefits, risks, alternatives, and therapy requirements, to answer all questions, and to facilitate SDM 73 prior to starting therapy. While a few chose to opt out through the survey, data presented here were 74 primarily collected through direct verbal communication between the caregiver and the provider. 75

Providers followed up after each consult visit to assess readiness to start therapy. If the family declined 76 to schedule a consult or start therapy, the guardian was asked an open-ended question regarding the 77 reason for decline and the provider recorded the response. The authors reviewed all qualitative answers 78 and sorted into general thematic categories. 79

Patient demographics are described in Table 1 . For patients on the peanut OIT waitlist, including 80 those who ultimately elected to begin therapy, the majority were Caucasian [48 (71%), and 12 (100%), 81 respectively], and held private insurance [56 (83.5%), and 12 (100%), respectively]. Figure 1 shows the 82 disposition of the 67 patients contacted. Nineteen (28%) declined therapy pre-consult, and 32 (48%) 83 completed consults; of these 32, 12 (18%) began therapy, and 15 (22%) declined therapy post-consult. 84

Additionally, 2 were referred for a peanut oral food challenge (OFC) after their consult, with both 85 passing the challenge; 1 was ineligible to start therapy due to a medical comorbidity (uncontrolled patients remaining, at the time of this writing, 3 are scheduled for future consults; 8 have not returned 88 multiple phone calls; 1 did not show for consult visit; and 4 were ineligible due to age. As shown in 89 Figure E1 , the most common rationales to decline therapy pre-consult and post-consult, respectively, 90 were time burden associated with therapy and the daily lifestyle modifications required to safely dose. 91

In total, 35 of 67 (52%) patients declined therapy, citing the following primary barriers: time burden in 92 10 (28.5%); lifestyle modifications in 9 (25%); multiple food allergies in 3 (8.5%); COVID-19 concerns in 3 93 (8.5%); family circumstances (e.g. pregnancy, relocation) in 3 (8.5%); previous peanut OIT failures at an 94 outside practice in 2 (6%); anxiety in 2 (6%); safety concerns in 1 (3%); cost of therapy in 1 (3%); and 95 unknown (lost to follow up post-consult) in 1 (3%). 96

Over half of our waitlist population declined therapy, with structural issues inherent to OIT dosing 97 such as lifestyle modifications and the time burden associated with therapy being the most common 98 reasons to decline. This has important implications for SDM in the general population, as these 99

considerations are intrinsic to therapy and generally not flexible . We dosed the first patient with 100 Palforzia on 13 March 2020, two days after the World Health Organization declared SARS-CoV-2 a global 101 pandemic, and as such these data represent some of the earliest known insights into how the pandemic 102 has affected the rollout of commercial OIT treatment programs. Interestingly, we observed that few 103 families reported the pandemic as a reason for decline. However, COVID-19 concerns may be under-104 reported in this population, as families with such concerns may have chosen not to engage with our 105 team at this time. Anxiety or other mental health concerns were also not widely cited as a reason for 106 decline, though this may also be under-reported due its stigma. Additional limitations of this quality 107 improvement project include the delivery of the survey to caregivers directly by the provider, which may 108 have inadvertently influenced the respondents' answers; the single-site and academic setting of the 109 project; the pre-selection of participants via a clinic waitlist; the skewing of the population towards 110 white race and private insurance; and loss to follow-up. 111

The practice of OIT continues to grow, and the widespread availability of a highly effective, 112 reimbursable standardized product will continue to shape the evolving standard of care. As these trends 113 continue, access to OIT will increasingly include the general population of food allergy patients, which 114 may differ in important ways from the highly motivated and resourced "early adopter" populations 115 profiled in prior studies. Our data suggest that half or more of patients and families that initially express 116 interest may ultimately decline, and that the lifestyle and time commitments required for OIT may 117 represent more important barriers than safety, mental health concerns, or even the COVID-19 118 pandemic. Much more work is needed to better understand the underlying factors that drive treatment 119 decisions in food allergy, and to ensure equitable access regardless of background or income. 120 

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Legend for Figure 1: 121 122 +Medical comorbidity that excluded patient participation in OIT: uncontrolled asthma