Dataset Information

Open-label follow-on study evaluating the efficacy, safety, and quality of life with extended daily oral immunotherapy in children with peanut allergy.

ABSTRACT:

Background

The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH)-formerly AR101-has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy-related quality of life.

Methods

We present a subset analysis of PALISADE-ARC004 participants (aged 4-17 years) who received 300 mg PTAH daily for a total of ~1.5 (Group A, n = 110) or ~2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double-blind, placebo-controlled food challenge (DBPCFC); skin prick testing; peanut-specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores.

Results

Continued maintenance with PTAH increased participants' ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose-limiting symptoms. Immune biomarkers showed a pattern consistent with treatment-induced desensitization. Among PTAH-continuing participants, the overall and treatment-related exposure-adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life.

Conclusions

These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response.

SUBMITTER: Fernandez-Rivas M

PROVIDER: S-EPMC9293305 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundConsortium for Food Allergy Research investigators previously reported 52-week outcomes from a randomized controlled trial of peanut epicutaneous immunotherapy, observing modest and statistically significant induction of desensitization, highest in children ages 4 to 11 years.ObjectiveWe sought to evaluate changes in efficacy, safety, and mechanistic parameters following extended open-label peanut epicutaneous immunotherapy.MethodsPeanut-allergic participants (4-25 years) received 52 weeks of placebo (PLB), Viaskin Peanut 100 μg (VP100) or 250 μg (VP250), and then crossed over to VP250 for PLB (PLB-VP250) and VP100 (VP100-VP250) participants and continued treatment for VP250 participants (total = 130 weeks of active epicutaneous immunotherapy). Efficacy was assessed by double-blind, placebo-controlled food challenge (5044 mg peanut protein), and adherence, safety, and mechanistic parameters were evaluated.ResultsAt week 130, desensitization success was achieved in 1 of 20 (5%) PLB-VP250, 5 of 24 (20.8%) VP100-VP250, and 9 of 25 (36%) VP250 participants, with median successfully consumed dose change from baseline of 11.5 mg, 141.5 mg, and 400 mg, respectively. Median age (years) for week 130 desensitization success was 6.2 years (interquartile range, 5.2-9.1) versus 9.4 years (interquartile range, 7.6-12.8) for failures (P < .001). Adherence was 96%. Adverse reactions were predominantly local patch-site reactions. Significant increases in peanut- and Ara h2-specific IgG4 observed at week 52 persisted to week 130. By a post hoc analysis, there were no statistically significant increases from week 52 to week 130 in either desensitization success or successfully consumed dose.ConclusionsExtended treatment with VP250 was well tolerated, and desensitization observed at week 52 persisted between weeks 52 and 130. Treatment success was observed predominantly in younger participants, with younger age at initiation of active therapy an important predictor of success.

Project description:IntroductionPeanut allergy is the the most common cause of life-threatening food-induced anaphylaxis. There is currently no effective long-term treatment. There is a pressing need for definitive treatments that improve the quality of life and prevent fatalities. Allergen oral immunotherapy (OIT) is a promising approach, which is effective at inducing desensitisation; however, OIT has a limited ability to induce sustained unresponsiveness (SU). We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut OIT (Probiotic Peanut Oral ImmunoTherapy (PPOIT)) is highly effective at inducing SU, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. Here we describe the protocol for a Phase IIb multicentre, double-blind, randomised, controlled trial (PPOIT-003) with dual primary objectives to evaluate the effectiveness of PPOIT at inducing SU (assessed at 8 weeks after treatment cessation) compared with placebo treatment and peanut OIT alone, in children with peanut allergy.Methods and analysis200 children 1 to 10 years of age with current peanut allergy confirmed by failed double-blind placebo-controlled food challenge (DBPCFC) at study screening will be recruited from three tertiary paediatric hospitals in Australia. There are three intervention arms-PPOIT, peanut OIT alone or placebo. Interventions are administered once daily for 18 months. The dual primary outcomes are: (1) the proportion of children who attain 8-week SU in the PPOIT group versus placebo group and (2) the proportion of children who attain 8-week SU in the PPOIT group versus OIT group.Ethics and disseminationThis study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 35246) and the Child and Adolescent Health Service (RGS 2543). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences.Trial registration numberACTRN12616000322437.

Project description:ObjectiveTo compared the cost-effectiveness of coadministration of a probiotic adjuvant with peanut oral immunotherapy (PPOIT) with placebo (no treatment) in children with peanut allergy.DesignProspectively planned cost-effectiveness analysis alongside a randomised control trial.SettingThe Royal Children's Hospital, Melbourne, Australia.Participants56 children with peanut allergy aged 1-10 years at recruitment.InterventionA daily dose of probiotic Lactobacillus rhamnosus CGMCC 1.3724 (NCC4007) and peanut oral immunotherapy administered for 1.5 years.Main outcomes measuresCosts were considered from a healthcare system perspective and included costs of treatment delivery and adverse events. Effectiveness outcomes included rate of sustained unresponsiveness (SU) and quality-adjusted life years (QALYs). The cost-effectiveness of PPOIT versus placebo was analysed using patient-level data. Time horizon was 10 years from commencement of PPOIT treatment, comprising 1.5 years of treatment (actual data), 4 years of post-treatment follow-up (actual data), and 4.5 years of extrapolation thereafter (modelling).ResultsHealthcare cost per patient over 10 years was higher for PPOIT compared with placebo ($A9355 vs $A1031, p<0.001). Over half of the per patient healthcare cost (53%) in the PPOIT group was attributable to treatment delivery, while the remaining cost was attributable to adverse events. Both measures of effectiveness were superior in the PPOIT group: the average SU rate over 10 years was 54% for PPOIT versus 6% for placebo (p<0.001); QALYs over 10 years were 9.05 for PPOIT versus 8.63 for placebo (p<0.001). Overall, cost per year of SU achieved was $A1694 (range $A1678, $A1709) for PPOIT compared with placebo, and cost per additional QALY gained was $A19 386 (range $A19 024, $A19 774).ConclusionsCost per QALY gained using PPOIT compared with no treatment is approximately $A20 000 (£10 000) and is well below the conventional value judgement threshold of $A50 000 (£25 000) per QALY gained, thus deemed good value for money ($A1= £0.5 approximately).Trial registration numberAustralian New Zealand Clinical Trials Registry ACTRN12608000594325; Post-results.