Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion among Children with Peanut Allergy: The PEPITES Randomized Clinical Trial

David M. Fleischer, Matthew Greenhawt, Gordon Sussman, Philippe Bégin, Anna Nowak-Wegrzyn, Daniel Petroni, Kirsten Beyer, Terri Brown-Whitehorn, Jacques Hebert, Jonathan O.B. Hourihane, Dianne E. Campbell, Stephanie Leonard, R. Sharon Chinthrajah, Jacqueline A. Pongracic, Stacie M. Jones, Lars Lange, Hey Chong, Todd D. Green, Robert Wood, Amarjit CheemaSusan L. Prescott, Peter Smith, William Yang, Edmond S. Chan, Aideen Byrne, Amal Assa'Ad, John A Bird, Edwin H. Kim, Lynda Schneider, Carla M. Davis, Bruce J. Lanser, Romain Lambert, Wayne Shreffler

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Importance: There are currently no approved treatments for peanut allergy. Objective: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n = 356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein. Interventions: Daily treatment with peanut patch containing either 250 μg of peanut protein (n = 238) or placebo (n = 118) for 12 months. Main Outcomes and Measures: The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs). Results: Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% [95% CI, 12.4%-29.8%; P <.001]). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group. Conclusions and Relevance: Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-μg peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined.

Original languageEnglish (US)
Pages (from-to)946-955
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume321
Issue number10
DOIs
StatePublished - Mar 12 2019

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Peanut Hypersensitivity
Immunotherapy
Randomized Controlled Trials
Eating
Placebos
Proteins
Therapeutics
Arachis
Confidence Intervals
Immediate Hypersensitivity
Food
Anaphylaxis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion among Children with Peanut Allergy : The PEPITES Randomized Clinical Trial. / Fleischer, David M.; Greenhawt, Matthew; Sussman, Gordon; Bégin, Philippe; Nowak-Wegrzyn, Anna; Petroni, Daniel; Beyer, Kirsten; Brown-Whitehorn, Terri; Hebert, Jacques; Hourihane, Jonathan O.B.; Campbell, Dianne E.; Leonard, Stephanie; Chinthrajah, R. Sharon; Pongracic, Jacqueline A.; Jones, Stacie M.; Lange, Lars; Chong, Hey; Green, Todd D.; Wood, Robert; Cheema, Amarjit; Prescott, Susan L.; Smith, Peter; Yang, William; Chan, Edmond S.; Byrne, Aideen; Assa'Ad, Amal; Bird, John A; Kim, Edwin H.; Schneider, Lynda; Davis, Carla M.; Lanser, Bruce J.; Lambert, Romain; Shreffler, Wayne.

In: JAMA - Journal of the American Medical Association, Vol. 321, No. 10, 12.03.2019, p. 946-955.

Research output: Contribution to journalArticle

Fleischer, DM, Greenhawt, M, Sussman, G, Bégin, P, Nowak-Wegrzyn, A, Petroni, D, Beyer, K, Brown-Whitehorn, T, Hebert, J, Hourihane, JOB, Campbell, DE, Leonard, S, Chinthrajah, RS, Pongracic, JA, Jones, SM, Lange, L, Chong, H, Green, TD, Wood, R, Cheema, A, Prescott, SL, Smith, P, Yang, W, Chan, ES, Byrne, A, Assa'Ad, A, Bird, JA, Kim, EH, Schneider, L, Davis, CM, Lanser, BJ, Lambert, R & Shreffler, W 2019, 'Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion among Children with Peanut Allergy: The PEPITES Randomized Clinical Trial', JAMA - Journal of the American Medical Association, vol. 321, no. 10, pp. 946-955. https://doi.org/10.1001/jama.2019.1113
Fleischer, David M. ; Greenhawt, Matthew ; Sussman, Gordon ; Bégin, Philippe ; Nowak-Wegrzyn, Anna ; Petroni, Daniel ; Beyer, Kirsten ; Brown-Whitehorn, Terri ; Hebert, Jacques ; Hourihane, Jonathan O.B. ; Campbell, Dianne E. ; Leonard, Stephanie ; Chinthrajah, R. Sharon ; Pongracic, Jacqueline A. ; Jones, Stacie M. ; Lange, Lars ; Chong, Hey ; Green, Todd D. ; Wood, Robert ; Cheema, Amarjit ; Prescott, Susan L. ; Smith, Peter ; Yang, William ; Chan, Edmond S. ; Byrne, Aideen ; Assa'Ad, Amal ; Bird, John A ; Kim, Edwin H. ; Schneider, Lynda ; Davis, Carla M. ; Lanser, Bruce J. ; Lambert, Romain ; Shreffler, Wayne. / Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion among Children with Peanut Allergy : The PEPITES Randomized Clinical Trial. In: JAMA - Journal of the American Medical Association. 2019 ; Vol. 321, No. 10. pp. 946-955.
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abstract = "Importance: There are currently no approved treatments for peanut allergy. Objective: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n = 356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein. Interventions: Daily treatment with peanut patch containing either 250 μg of peanut protein (n = 238) or placebo (n = 118) for 12 months. Main Outcomes and Measures: The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15{\%} or more on the lower bound of a 95{\%} CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs). Results: Among 356 participants randomized (median age, 7 years; 61.2{\%} male), 89.9{\%} completed the trial; the mean treatment adherence was 98.5{\%}. The responder rate was 35.3{\%} with peanut-patch treatment vs 13.6{\%} with placebo (difference, 21.7{\%} [95{\%} CI, 12.4{\%}-29.8{\%}; P <.001]). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4{\%} and 89{\%} of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5{\%} in the peanut-patch group vs 9.3{\%} in the placebo group. Conclusions and Relevance: Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-μg peanut-patch therapy vs placebo was 21.7{\%} and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined.",
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T1 - Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion among Children with Peanut Allergy

T2 - The PEPITES Randomized Clinical Trial

AU - Fleischer, David M.

AU - Greenhawt, Matthew

AU - Sussman, Gordon

AU - Bégin, Philippe

AU - Nowak-Wegrzyn, Anna

AU - Petroni, Daniel

AU - Beyer, Kirsten

AU - Brown-Whitehorn, Terri

AU - Hebert, Jacques

AU - Hourihane, Jonathan O.B.

AU - Campbell, Dianne E.

AU - Leonard, Stephanie

AU - Chinthrajah, R. Sharon

AU - Pongracic, Jacqueline A.

AU - Jones, Stacie M.

AU - Lange, Lars

AU - Chong, Hey

AU - Green, Todd D.

AU - Wood, Robert

AU - Cheema, Amarjit

AU - Prescott, Susan L.

AU - Smith, Peter

AU - Yang, William

AU - Chan, Edmond S.

AU - Byrne, Aideen

AU - Assa'Ad, Amal

AU - Bird, John A

AU - Kim, Edwin H.

AU - Schneider, Lynda

AU - Davis, Carla M.

AU - Lanser, Bruce J.

AU - Lambert, Romain

AU - Shreffler, Wayne

PY - 2019/3/12

Y1 - 2019/3/12

N2 - Importance: There are currently no approved treatments for peanut allergy. Objective: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n = 356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein. Interventions: Daily treatment with peanut patch containing either 250 μg of peanut protein (n = 238) or placebo (n = 118) for 12 months. Main Outcomes and Measures: The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs). Results: Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% [95% CI, 12.4%-29.8%; P <.001]). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group. Conclusions and Relevance: Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-μg peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined.

AB - Importance: There are currently no approved treatments for peanut allergy. Objective: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n = 356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein. Interventions: Daily treatment with peanut patch containing either 250 μg of peanut protein (n = 238) or placebo (n = 118) for 12 months. Main Outcomes and Measures: The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs). Results: Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% [95% CI, 12.4%-29.8%; P <.001]). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group. Conclusions and Relevance: Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-μg peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined.

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