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

EClinicalMedicine (Jan 2019)

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

Affiliations

Sandra Andorf: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA
Natasha Purington: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA
Divya Kumar: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA
Andrew Long: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA
Katherine L. O'Laughlin: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA
Scott Sicherer: Division of Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Hugh Sampson: Division of Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Antonella Cianferoni: 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
Terri Brown Whitehorn: 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
Daniel Petroni: ASTHMA Inc. Clinical Research Center, Northwest Asthma and Allergy Center, University of Washington, Seattle, WA, USA
Melanie Makhija: Division of Allergy and Immunology, the Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
Rachel G. Robison: Division of Allergy and Immunology, the Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
Michelle Lierl: Division of Allergy and Immunology, Cincinnati Children's Medical Center, Cincinnati, OH, USA
Stephanie Logsdon: Division of Allergy and Immunology, Cincinnati Children's Medical Center, Cincinnati, OH, USA
Manisha Desai: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA
Stephen J. Galli: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA
Efren Rael: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA
Amal Assa'ad: Division of Allergy and Immunology, Cincinnati Children's Medical Center, Cincinnati, OH, USA
Sharon Chinthrajah: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA
Jacqueline Pongracic: Division of Allergy and Immunology, the Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
Jonathan M. Spergel: 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
Jonathan Tam: Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles, Los Angeles, CA, USA
Stephen Tilles: ASTHMA Inc. Clinical Research Center, Northwest Asthma and Allergy Center, University of Washington, Seattle, WA, USA
Julie Wang: Division of Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Kari Nadeau: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA; Corresponding author at: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, 269 Campus Drive, CCSR 3215, MC 5366, Stanford, CA 94305-5101, USA.

Journal volume & issue: Vol. 7
pp. 27 – 38

Abstract

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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 allergy, Oral immunotherapy, Omalizumab, Sustained unresponsiveness, Food allergen

Published in EClinicalMedicine

ISSN: 2589-5370 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General)
Website: https://www.thelancet.com/journals/eclinm/home

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