Josef Brandström1,2, Mirja Vetander1,3,4, Ann-Charlotte Sundqvist1, Gunnar Lilja1,2, S G O Johansson1,2, Erik Melén1,3, Eva Sverremark-Ekström5, Anna Nopp1,2, Caroline Nilsson1,2. 1. Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden. 2. Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden. 3. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 4. Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden. 5. Department of Molecular Biosciences, TheWenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Abstract
BACKGROUND: Peanut oral immunotherapy (pOIT) has showed good short-term outcomes, but allergic reactions may prevent effective up-dosing and is a major cause of stopping OIT. In placebo-controlled trials, omalizumab has been shown to facilitate allergen immunotherapy and increase tolerance to peanut. OBJECTIVE: We hypothesized that by combining omalizumab with pOIT, and monitor treatment effects with basophil allergen threshold sensitivity tests (CD-sens), peanut allergic patients could safely initiate pOIT and thereafter slowly withdraw omalizumab. METHODS: This is the 2nd part of a one-armed open phase-2 study where peanut allergic adolescents (n = 23) started pOIT after an individualized omalizumab treatment. The pOIT dose was increased from 280 to 2800 mg peanut protein in 8 weeks followed by an individualized step-wise withdrawal of omalizumab, based on clinical symptoms and CD-sens levels. pOIT continued for 12 weeks followed by an open peanut challenge. Peanut CD-sens and allergen-binding activity (ABA) and IgE-ab, IgG-ab and IgG4-ab to peanut and its components were measured during the study. RESULTS: All 23 patients successfully reached the 2800 mg maintenance dose. Moderate/systemic allergic reactions were rare while receiving full-dose omalizumab. Eleven of 23 (48%) successfully continued with pOIT after omalizumab was stopped. Compared to treatment failures, median baseline IgE-ab to peanut components Ara h 1-3 and CD-sens to peanut were significantly lower among successfully treated patients and IgG4-ab to peanut, Ara h 2 and 6 increased significantly more during treatment. CONCLUSIONS AND CLINICAL RELEVANCE: This study indicates that omalizumab is an effective adjunctive therapy for initiation and rapid up-dosing of pOIT; however, adverse events from pOIT become more frequent as omalizumab doses are decreased. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; NCT02402231. EudraCT; 2012-005625-78.
BACKGROUND:Peanut oral immunotherapy (pOIT) has showed good short-term outcomes, but allergic reactions may prevent effective up-dosing and is a major cause of stopping OIT. In placebo-controlled trials, omalizumab has been shown to facilitate allergen immunotherapy and increase tolerance to peanut. OBJECTIVE: We hypothesized that by combining omalizumab with pOIT, and monitor treatment effects with basophil allergen threshold sensitivity tests (CD-sens), peanut allergic patients could safely initiate pOIT and thereafter slowly withdraw omalizumab. METHODS: This is the 2nd part of a one-armed open phase-2 study where peanut allergic adolescents (n = 23) started pOIT after an individualized omalizumab treatment. The pOIT dose was increased from 280 to 2800 mg peanut protein in 8 weeks followed by an individualized step-wise withdrawal of omalizumab, based on clinical symptoms and CD-sens levels. pOIT continued for 12 weeks followed by an open peanut challenge. PeanutCD-sens and allergen-binding activity (ABA) and IgE-ab, IgG-ab and IgG4-ab to peanut and its components were measured during the study. RESULTS: All 23 patients successfully reached the 2800 mg maintenance dose. Moderate/systemic allergic reactions were rare while receiving full-dose omalizumab. Eleven of 23 (48%) successfully continued with pOIT after omalizumab was stopped. Compared to treatment failures, median baseline IgE-ab to peanut components Ara h 1-3 and CD-sens to peanut were significantly lower among successfully treated patients and IgG4-ab to peanut, Ara h 2 and 6 increased significantly more during treatment. CONCLUSIONS AND CLINICAL RELEVANCE: This study indicates that omalizumab is an effective adjunctive therapy for initiation and rapid up-dosing of pOIT; however, adverse events from pOIT become more frequent as omalizumab doses are decreased. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; NCT02402231. EudraCT; 2012-005625-78.
Authors: El-Bdaoui Haddad; Sonya L Cyr; Kazuhiko Arima; Robert A McDonald; Noah A Levit; Frank O Nestle Journal: Dermatol Ther (Heidelb) Date: 2022-05-21
Authors: Monali Manohar; Diane Dunham; Sheena Gupta; Zheng Yan; Wenming Zhang; Samantha Minnicozzi; Matthew Kirkey; Bryan Bunning; Roshni Roy Chowdhury; Stephen J Galli; Scott D Boyd; Laurie Elizabeth Kost; R Sharon Chinthrajah; Manisha Desai; Hans C Oettgen; Holden T Maecker; Wong Yu; Rosemarie H DeKruyff; Sandra Andorf; Kari C Nadeau Journal: Allergy Date: 2021-05-29 Impact factor: 14.710