Peanut Oral Immunotherapy Improves Quality of Life More in Males vs Females

The study found that sex assigned at birth modified health-related quality of life (HRQL) outcomes in children with food allergies undergoing peanut oral immunotherapy, with males showing significant benefit from active treatment compared to placebo versus females.1

“An intriguing finding was that females benefitted significantly from placebo intervention primarily during the active treatment period while males did not; both males and females experienced comparable HRQL benefit from [oral immunotherapy],” wrote study investigator Sophie A. Rosser, PhD candidate, from Murdoch Children's Research Institute in Australia, and colleagues.1

Many children with food allergies and their caregivers have a reduced health-related quality of life. Rosser and colleagues previously conducted a systematic review examining HRQL differences between males and females during immunotherapy but were not unable to draw conclusions due to limited data.2

In this new study, the investigators examined whether sex influenced overall and subdomain HRQL outcomes in children receiving peanut oral immunotherapy.1 The PPOIT-003 trial, a 3-arm, multicenter, randomized controlled study, enrolled 201 children aged 1–10 years with peanut allergy. Participants, recruited from Australian hospitals in Adelaide, Melbourne, and Perth, met eligibility criteria if they weighed ≥ 7 kg, had an IgE-mediated peanut allergy confirmed by a failed double-blind placebo-controlled food challenge, and a positive peanut skin prick test or peanut-specific serum-IgE at screening.

The team randomized participants 2:2:1 to receive combined probiotic plus peanut oral immunotherapy (PPOIT), peanut oral immunotherapy alone, or placebo for 18 months. They measured HRQL using the Food Allergy Quality of Life-Parent Form (FAQLQ-PF) at baseline, end-of-treatment, and 12 months post-treatment.1

Moreover, they used multivariable linear regression to assess the relationship between treatment and HRQL in males (n = 128; 63.68%) and females (n = 73; 36.32%). Each arm had a comparable proportion of males and females, although the study included more males.1

Among male participants, 39.58% receiving POIT and 49% receiving oral immunotherapy achieved remission at the end of treatment. As for females, 54.84% with PPOINT and 53.57% with oral immunotherapy achieved remission. Only 1 male and 1 female receiving a placebo achieved remission.1

Sex significantly influenced FAQLQ-PF total scores over the full study period (P =.008). The analysis showed that, compared with males receiving placebo, males receiving PPOIT (−1.003; 95% confidence interval [CI], −1.571 to −0.436) or peanut oral immunotherapy (−1.250; 95% CI, −1.805 to −0.695) had significantly better improvement in FAQLQ-PF scores. However, females in both the active and placebo arm experienced improvement in FAQLQ-PF scores (PPOIT vs. placebo: −0.148; 95% CI, −0.914 to 0.617 and OIT vs. placebo: 0.252; 95% CI, −0.547 to 1.052); the strong placebo response in females could be attributed to sex differences.1

Given that females in both the active and placebo arms experienced comparable HRQL improvement, the team wrote that this suggests that supportive strategies, such as counseling or education, may meaningfully enhance outcomes for young females. Conversely, the findings indicate that support-based approaches may be less impactful for male children.

A separate analysis on study phases showed that sex modified quality of life more during treatment than during treatment follow-up (P = .066 vs P = .254). Investigators noted that sex may have had a greater impact on quality of life during active therapy due to contextual factors, such as patient-provider interactions. The strongest sex differences emerged in HRQL measures tied to food anxiety (P = .037) and the emotional toll of food allergy (P = .063).1

“While effect modification by sex occurred primarily during active therapy, exploration of other patient demographic characteristics, during-treatment factors (such as adverse events and achievement of maintenance), and post-treatment factors (such as peanut consumption and post-treatment remission and desensitization outcomes) on HRQL is still needed to better inform personalized [oral immunotherapy] approaches and should be prioritized in future research,” investigators wrote.1

References

1. Rosser SA, Lloyd M, Loke P, et al. Sex assigned at birth may modify health-related quality of life in children treated with peanut oral immunotherapy. Pediatr Allergy Immunol. 2025;36(8):e70177. doi:10.1111/pai.70177

2. Rosser SA, Lloyd M, Hu A, Loke P, Tang MLK. Associations between gender and health-related quality of life in people with IgE-mediated food allergy and their caregivers: A systematic review. Clin Exp Allergy. 2024;54(2):93-108. doi:10.1111/cea.14450