A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued vs Discontinued Dosing in Multifood Allergic Individuals

Sandra Andorf; Natasha Purington; Divya Kumar; Andrew Long; Katherine L O'Laughlin; Scott Sicherer; Hugh Sampson; Antonella Cianferoni; Terri Brown Whitehorn; Daniel Petroni; Melanie Makhija; Rachel G Robison; Michelle Lierl; Stephanie Logsdon; Manisha Desai; Stephen J Galli; Efren Rael; Amal Assa'ad; Sharon Chinthrajah; Jacqueline Pongracic; Jonathan M Spergel; Jonathan Tam; Stephen Tilles; Julie Wang; Kari Nadeau

doi:10.1016/j.eclinm.2018.12.006

A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued vs Discontinued Dosing in Multifood Allergic Individuals

EClinicalMedicine. 2019 Jan 21:7:27-38. doi: 10.1016/j.eclinm.2018.12.006. eCollection 2019 Jan.

Authors

Sandra Andorf^{1

2

3}, Natasha Purington^{1

2

3}, Divya Kumar^{1

2

3}, Andrew Long^{1

2

3}, Katherine L O'Laughlin^{1

2

3}, Scott Sicherer⁴, Hugh Sampson⁴, Antonella Cianferoni⁵, Terri Brown Whitehorn⁵, Daniel Petroni⁶, Melanie Makhija⁷, Rachel G Robison⁷, Michelle Lierl⁸, Stephanie Logsdon⁸, Manisha Desai^{1

2

3}, Stephen J Galli^{1

9

10}, Efren Rael^{1

2

3}, Amal Assa'ad⁸, Sharon Chinthrajah^{1

2

3}, Jacqueline Pongracic⁷, Jonathan M Spergel⁵, Jonathan Tam¹¹, Stephen Tilles⁶, Julie Wang⁴, Kari Nadeau^{1

2

3}

Affiliations

¹ Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA.
² Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA.
³ Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA.
⁴ Division of Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵ Division of Allergy and Immunology, The Children's Hospital of Philadelphia Department of Pediatrics, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA.
⁶ ASTHMA Inc. Clinical Research Center, Northwest Asthma and Allergy Center, University of Washington, Seattle, WA, USA.
⁷ Division of Allergy and Immunology, the Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
⁸ Division of Allergy and Immunology, Cincinnati Children's Medical Center, Cincinnati, OH, USA.
⁹ Department of Pathology, Stanford University, Stanford, CA, USA.
¹⁰ Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
¹¹ Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles, Los Angeles, CA, USA.

Abstract

Background: As there is limited data on the sustainability of desensitization of multifood-oral immunotherapy (multifood-OIT), we conducted a multisite multifood-OIT study to compare the efficacy of successful desensitization with sustained dosing vs discontinued dosing after multifood-OIT.

Methods: We enrolled 70 participants, aged 5-22 years with multiple food allergies confirmed by double-blind placebo-controlled food challenges (DBPCFCs). In the open-label phase of the study, all participants received omalizumab (weeks 1-16) and multi-OIT (2-5 allergens; weeks 8-30) and eligible participants (on maintenance dose of each allergen by weeks 28-29) were randomized 1:1:1 to 1 g, 300 mg, or 0 mg arms (blinded, weeks 30-36) and then tested by food challenge at week 36. Success was defined as passing 2 g food challenge to at least 2 foods in week 36.

Findings: Most participants were able to reach a dose of 2 g or higher of each of 2, 3, 4, and 5 food allergens (as applicable to the participant's food allergens in OIT) in week 36 food challenges. Using an intent-to-treat analysis, we did not find evidence that a 300 mg dose was effectively different than a 1 g dose in maintaining desensitization, and both together were more effective than OIT discontinuation (0 mg dose) (85% vs 55%, P = 0.03). Fifty-five percent of the intent-to-treat participants and 69% of per protocol participants randomized to the 0 mg arm showed no objective reactivity after 6 weeks of discontinuation. Cross-desensitization was found between cashew/pistachio and walnut/pecan when only one of the foods was part of OIT. No statistically significant safety differences were found between the three arms.

Interpretation: These results suggest that sustained desensitization after omalizumab-facilitated multi-OIT best occurs through continued maintenance OIT dosing of either 300 mg or 1 g of each food allergen as opposed to discontinuation of multi-OIT.

Funding: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Jeff and MacKenzie Bezos, NIAID AADCRC U19AI104209.

Trial registration number: ClinicalTrials.gov number, NCT02626611.

Keywords: Food allergen; Food allergy; Omalizumab; Oral immunotherapy; Sustained unresponsiveness.

Associated data

ClinicalTrials.gov/NCT02626611

Abstract

Associated data

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