Headline
This study aimed to determine the efficacy of peanut oral immunotherapy (OIT) in children. In children with peanut allergy of any severity, OIT successfully induced desensitisation in the majority, with a clinically meaningful increase in peanut threshold. Quality of life improved after intervention and there was a good safety profile. Immunological changes reflected clinical desensitisation and side effects were mild in most, with gastrointestinal symptoms being the most common. Future work will include a phase 3 confirmatory study and studies of long-term tolerance; similar studies of other allergens are also required.
Abstract
Background:
Peanut allergy is a common disease that causes severe and fatal food allergic reactions. Currently, the best treatment is avoidance as repeated reactions can occur. Quality of life (QoL) is reduced by fear of severe reactions and social limitations. Oral immunotherapy (OIT) is a novel treatment that may be an effective treatment for peanut allergy.
Objectives:
To determine the efficacy of peanut OIT in children.
Design:
A phase 2 randomised, controlled, crossover trial (open label).
Setting:
Single UK centre study.
Participants:
Children aged 7–15 years with peanut allergy diagnosed by double-blind, placebo-controlled food challenge (DBPCFC). No children were excluded because of anaphylaxis or asthma.
Interventions:
Daily immunotherapy (2
mg, 5mg, 12.5mg, 25mg, 50mg, 100mg, 200mg, 400mg and 800mg of peanut protein) was administered as peanut flour (containing 50% peanut protein). Doses were increased at 2-weekly intervals to a maintenance dose of 800mg of protein. The control group underwent peanut avoidance for 6 months during phase 1.
mg, 5mg, 12.5mg, 25mg, 50mg, 100mg, 200mg, 400mg and 800mg of peanut protein) was administered as peanut flour (containing 50% peanut protein). Doses were increased at 2-weekly intervals to a maintenance dose of 800mg of protein. The control group underwent peanut avoidance for 6 months during phase 1.
Main outcome measure:
A peanut DBPCFC up to 1400mg of peanut protein was performed in both groups at 6 months. The highest amount of peanut tolerated was the main outcome measure.
mg of peanut protein was performed in both groups at 6 months. The highest amount of peanut tolerated was the main outcome measure.
Randomisation:
Randomised by online audited system to active or control group (1:1).
:1).Blinding:
The intervention arm allocation was not blinded.
Methods:
We assigned 99 participants aged 7–16 years with peanut allergy of all severities to active OIT or control (peanut avoidance/current standard of care). The primary outcome was desensitisation, defined as negative peanut challenge (1400mg of protein DBPCFC) at 6 months (phase 1). Control participants underwent OIT during phase 2, followed by DBPCFC. Immunological parameters and disease-specific QoL scores were measured.
mg of protein DBPCFC) at 6 months (phase 1). Control participants underwent OIT during phase 2, followed by DBPCFC. Immunological parameters and disease-specific QoL scores were measured.
Results:
The primary outcome, desensitisation, was observed in 62% (24/39) of the active group and none (0/46) of the control group after phase 1 [95% confidence interval (CI) 45% to 78% vs. 0% to 9%; p<0.001]; 84% (95% CI 70% to 93%) of the active group tolerated daily ingestion of 800mg of protein (≈five peanuts). Median increase in peanut threshold after OIT was 1345mg (range 45–1400mg; p<0.001) or 2.5-fold (range 1.82–280-fold; p<0.001). After phase 2, 54% (95% CI 35% to 72%) tolerated a 1400-mg challenge (≈10 peanuts) and 91% (95% CI 79% to 98%) tolerated a daily ingestion of 800mg of protein. QoL scores improved (decreased) after OIT (median change –1.61; p<0.001). Side effects were mostly mild with gastrointestinal symptoms being the most common: oral pruritus occurred after 6.3% of doses, wheeze occurred after 0.41% of doses (one-fifth of participants) and intramuscular epinephrine was required after 0.01% of doses (one participant).
<0.001]; 84% (95% CI 70% to 93%) of the active group tolerated daily ingestion of 800mg of protein (≈five peanuts). Median increase in peanut threshold after OIT was 1345mg (range 45–1400mg; p<0.001) or 2.5-fold (range 1.82–280-fold; p<0.001). After phase 2, 54% (95% CI 35% to 72%) tolerated a 1400-mg challenge (≈10 peanuts) and 91% (95% CI 79% to 98%) tolerated a daily ingestion of 800mg of protein. QoL scores improved (decreased) after OIT (median change –1.61; p<0.001). Side effects were mostly mild with gastrointestinal symptoms being the most common: oral pruritus occurred after 6.3% of doses, wheeze occurred after 0.41% of doses (one-fifth of participants) and intramuscular epinephrine was required after 0.01% of doses (one participant).
Conclusion:
In children with peanut allergy of any severity, OIT successfully induced desensitisation in the majority, with a clinically meaningful increase in peanut threshold. QoL improved after intervention and there was a good safety profile. Immunological changes reflected clinical desensitisation. Peanut OIT should not be undertaken in non-specialist settings. Future work will include a phase 3 confirmatory study and studies of long-term tolerance; similar studies of other allergens are also required.
Trial registration:
Current Controlled Trials ISRCTN62416244.
Funding:
This project was awarded by the Efficacy and Mechanism Evaluation programme and is funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC–NIHR partnership, and jointly sponsored by the University of Cambridge and Addenbrooke’s Hospital [Cambridge University Hospital Foundation Trust (RD authorisation A091686)]. The project will be published in full in Efficacy and Mechanism Evaluation; Vol. 1, No. 4. See the NIHR Journals Library website for further project information.
Contents
Article history
The research reported in this issue of the journal was funded by the EME programme as project number 08/99/18. The contractual start date was in January 2010. The final report began editorial review in July 2013 and was accepted for publication in April 2014. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The EME editors and production house have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the final report document. However, they do not accept liability for damages or losses arising from material published in this report.
Declared competing interests of authors
Andrew Clark and Pamela Ewan are inventors on a patent application covering the peanut protein dose range.
Copyright © Queen’s Printer and Controller of HMSO 2014. This work was produced by Anagnostou et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.
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