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. 2024 Jan;14(1):e12326.
doi: 10.1002/clt2.12326.

Exploratory immunogenicity outcomes of peanut oral immunotherapy: Findings from the PALISADE trial

Caroline Nilsson  1 , Andrea Vereda  2 , Magnus P Borres  3   4 , Mats Andersson  4 , Eva Södergren  4 , Magnus Rudengren  4 , Alex Smith  5 , Reyna J Simon  6 , Robert Ryan  2 , Montserrat Fernández-Rivas  7 , Daniel Adelman  5   8 , Brian P Vickery  9
Affiliations

Exploratory immunogenicity outcomes of peanut oral immunotherapy: Findings from the PALISADE trial

Caroline Nilsson et al. Clin Transl Allergy. 2024 Jan.

Abstract

Background: Immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) to peanut and its components may influence the clinical reactivity to peanut. Allergen-specific immunotherapy is known for modifying both IgE and IgG4. Peanut oral immunotherapy may influence these serological parameters.

Methods: Exploratory analyses of serological data from participants receiving peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) and placebo in the double-blind, randomized, phase 3 PALISADE trial were conducted to evaluate potential relationships between peanut-specific and peanut component-specific (Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, and Ara h 9) IgE and IgG4 levels and clinical outcomes.

Results: A total of 269 participants (PTAH, n = 202; placebo, n = 67) were analyzed. No relationship was observed between specific IgE and IgG4 levels at screening and maximum tolerated peanut protein dose during screening or response status during exit double-blind placebo-controlled food challenge (DBPCFC). In PTAH-treated participants, no relationship was observed between IgE and IgG4 levels at screening and maximum symptom severity during exit DBPCFC. Postscreening ratios (ie, postscreening/screening) in the PTAH group were significant at the end of updosing and exit visit for most components. Postscreening changes in specific IgE levels were more pronounced with PTAH versus placebo for most components.

Conclusions: Specific IgE and IgG4 levels at screening are not correlated with screening or exit DBPCFC results, and are not predictive of clinical response to PTAH. Peanut (Arachis hypogaea) allergen powder-dnfp contains the relevant and immunodominant allergens, inducing immunological changes with the treatment.

Clinical trial registration: ClinicalTrials.gov identifier: NCT02635776.

Keywords: immunoglobulin; oral immunotherapy; peanut; peanut allergy; serology.

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Conflict of interest statement

Caroline Nilsson: Grants to my institution and advisory board fees from Aimmune Therapeutics, a Nestlé Health Science company; lecture fees from ALK, GSK, MEDA, and Thermo Fisher; advisory board fees from Novartis. Andrea Vereda: Employee of Aimmune Therapeutics, a Nestlé Health Science company. Magnus P. Borres: Employee of Thermo Fisher Scientific. Mats Andersson: Employee of Thermo Fisher Scientific. Eva Södergren: Employee of Thermo Fisher Scientific. Magnus Rudengren: Employee of Thermo Fisher Scientific. Alex Smith: Former employee and shareholder of Aimmune Therapeutics, a Nestlé Health Science company. Reyna J. Simon: Former employee and shareholder of Aimmune Therapeutics, a Nestlé Health Science company. Robert Ryan: Employee of Aimmune Therapeutics, a Nestlé Health Science company. Montserrat Fernández‐Rivas: Grants to my institution, consulting fees, and payments or honoraria from Aimmune Therapeutics, a Nestlé Health Science company; consulting fees from Novartis, Reacta Healthcare, and SPRIM; payments or honoraria from ALK, Diater, Ediciones Mayo S.A., EPG Health, GSK, HAL Allergy, and Novartis; participation on a data safety monitoring board for DBV Technologies. Daniel Adelman: Former employee and shareholder of Aimmune Therapeutics, a Nestlé Health Science company. Brian P. Vickery: Grants to my institution from Aimmune Therapeutics, a Nestlé Health Science company, DBV Technologies, FARE, Genentech, NIH‐NIAID, and Regeneron; consulting fees from Aimmune Therapeutics, a Nestlé Health Science company, AllerGenis, Aravax, DBV Technologies, FARE, Reacta, and Regeneron. Former employee and former shareholder owner of Aimmune Therapeutics, a Nestlé Health Science company.

Figures

FIGURE 1
FIGURE 1
Disposition of participants included in immunoglobulin analyses. PTAH, peanut (Arachis hypogaea) allergen powder‐dnfp; UK, United Kingdom; US, United States.
FIGURE 2
FIGURE 2
Screening IgE (A) and IgG4 (B) levels by the maximum tolerated peanut protein dose during the screening DBPCFC. DBPCFC, double‐blind, placebo‐controlled food challenge; IgE, immunoglobulin E; IgG4, immunoglobulin G4.
FIGURE 3
FIGURE 3
Screening IgE (A) and IgG4 (B) levels by randomized treatment and response status to the 300 mg, 600 mg, and 1000 mg doses of the exit DBPCFC. Participants at each level of the tolerated dose also tolerated the dose levels below it (ie, those who tolerated 1000 mg of peanut protein at the exit DBPCFC also tolerated 300 mg and 600 mg). DBPCFC, double‐blind, placebo‐controlled food challenge; IgE, immunoglobulin E; IgG4, immunoglobulin G4; PTAH, peanut (Arachis hypogaea) allergen powder‐dnfp.
FIGURE 3
FIGURE 3
Screening IgE (A) and IgG4 (B) levels by randomized treatment and response status to the 300 mg, 600 mg, and 1000 mg doses of the exit DBPCFC. Participants at each level of the tolerated dose also tolerated the dose levels below it (ie, those who tolerated 1000 mg of peanut protein at the exit DBPCFC also tolerated 300 mg and 600 mg). DBPCFC, double‐blind, placebo‐controlled food challenge; IgE, immunoglobulin E; IgG4, immunoglobulin G4; PTAH, peanut (Arachis hypogaea) allergen powder‐dnfp.
FIGURE 4
FIGURE 4
Screening IgE levels by randomized treatment and maximum symptom severity during the exit DBPCFC. N/A corresponds to participants who did not perform the exit DBPCFC. DBPCFC, double‐blind, placebo‐controlled food challenge; IgE, immunoglobulin E; N/A, not applicable.
FIGURE 5
FIGURE 5
Geometric mean IgE levels (A), the geometric mean change from screening in IgE levels (B), geometric mean immunoglobulin G4 (IgG4) levels (C), and geometric mean change from screening in IgG4 levels (D) by randomized treatment and study visit. *0.01 < p ≤ 0.05, **0.001 < p ≤ 0.01, ***p ≤ 0.001. p values in panels B and D are from repeated measures model. CI, confidence interval; DBPCFC, double‐blind, placebo‐controlled food challenge; IgE, immunoglobulin E; IgG4, immunoglobulin G4; LCL, lower confidence limit; PTAH, peanut (Arachis hypogaea) allergen powder‐dnfp; UCL, upper confidence limit.
FIGURE 5
FIGURE 5
Geometric mean IgE levels (A), the geometric mean change from screening in IgE levels (B), geometric mean immunoglobulin G4 (IgG4) levels (C), and geometric mean change from screening in IgG4 levels (D) by randomized treatment and study visit. *0.01 < p ≤ 0.05, **0.001 < p ≤ 0.01, ***p ≤ 0.001. p values in panels B and D are from repeated measures model. CI, confidence interval; DBPCFC, double‐blind, placebo‐controlled food challenge; IgE, immunoglobulin E; IgG4, immunoglobulin G4; LCL, lower confidence limit; PTAH, peanut (Arachis hypogaea) allergen powder‐dnfp; UCL, upper confidence limit.
FIGURE 5
FIGURE 5
Geometric mean IgE levels (A), the geometric mean change from screening in IgE levels (B), geometric mean immunoglobulin G4 (IgG4) levels (C), and geometric mean change from screening in IgG4 levels (D) by randomized treatment and study visit. *0.01 < p ≤ 0.05, **0.001 < p ≤ 0.01, ***p ≤ 0.001. p values in panels B and D are from repeated measures model. CI, confidence interval; DBPCFC, double‐blind, placebo‐controlled food challenge; IgE, immunoglobulin E; IgG4, immunoglobulin G4; LCL, lower confidence limit; PTAH, peanut (Arachis hypogaea) allergen powder‐dnfp; UCL, upper confidence limit.
FIGURE 5
FIGURE 5
Geometric mean IgE levels (A), the geometric mean change from screening in IgE levels (B), geometric mean immunoglobulin G4 (IgG4) levels (C), and geometric mean change from screening in IgG4 levels (D) by randomized treatment and study visit. *0.01 < p ≤ 0.05, **0.001 < p ≤ 0.01, ***p ≤ 0.001. p values in panels B and D are from repeated measures model. CI, confidence interval; DBPCFC, double‐blind, placebo‐controlled food challenge; IgE, immunoglobulin E; IgG4, immunoglobulin G4; LCL, lower confidence limit; PTAH, peanut (Arachis hypogaea) allergen powder‐dnfp; UCL, upper confidence limit.
FIGURE 6
FIGURE 6
IgE (A) and IgG4 (B) treatment comparison by study visit (end of updosing and exit). *0.01 < p ≤ 0.05, **0.001 < p ≤ 0.01, ***p ≤ 0.001. p values are from repeated measures model. CI, confidence interval; IgE, immunoglobulin E; IgG4, immunoglobulin G4; PTAH, peanut (Arachis hypogaea) allergen powder‐dnfp.
FIGURE 6
FIGURE 6
IgE (A) and IgG4 (B) treatment comparison by study visit (end of updosing and exit). *0.01 < p ≤ 0.05, **0.001 < p ≤ 0.01, ***p ≤ 0.001. p values are from repeated measures model. CI, confidence interval; IgE, immunoglobulin E; IgG4, immunoglobulin G4; PTAH, peanut (Arachis hypogaea) allergen powder‐dnfp.
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