Immunotherapy raises risk in peanut allergy

Author: Mark Gould
Immunotherapy raises risk in peanut allergy

A major review* of children with peanut allergies has concluded that current oral immunotherapy treatments result in a large increase in anaphylaxis and other allergic reactions, rather than preventing them as intended.

The systematic review including 12 studies with more than 1,000 patients who were followed for a year finds that, compared with allergen avoidance or placebo, current oral immunotherapy increases risk.

The authors writing in The Lancet, say that their findings favour avoidance over current forms of oral immunotherapy if a patient wishes to avoid peanut-induced anaphylaxis and allergic reactions, and that the increased risk of reactions associated with these regimens might be a substantial barrier to widespread adoption by patients with peanut allergies.

They say their findings highlight the gap between outcomes measured in the clinic and the allergy relief outcomes that patients desire after oral immunotherapy for peanut allergy.

Studies of oral immunotherapy currently measure treatment success by whether a treated patient can pass a supervised food challenge, but this cannot predict a patient’s future risk and frequency of allergic reactions in the real world. The authors call for safer peanut allergy treatment approaches and rigorous randomised controlled trials, which use more appropriate measures of allergy reduction based on outcomes that patients want.

Lead author Dr Derek Chu, from McMaster University in Canada says the study shows that current peanut oral immunotherapy regimens can achieve the immunological goal of desensitisation, "but that this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis over time".

"Instead, the opposite outcome occurs, with more allergic and adverse reactions with oral immunotherapy compared with avoidance or placebo,” he says.

“Our results do not denounce current research in oral immunotherapy, but the method needs to be more carefully considered, improvements in safety made, and measures of success need to be aligned with patients’ wishes.”

The study combined results from 12 randomised controlled trials from the USA, UK, Europe and Australia (including three unpublished trials) including 1,041 patients to compare outcomes after oral immunotherapy with those after no oral immunotherapy. The trials compared oral immunotherapy against placebo, avoidance or other types of immunotherapy, and used different peanut products and doses.

The average age of participants in the studies was around nine years of age (between 5-12 years), and participants were followed for a year on average. The study measured anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life.

The results suggest with high and moderate quality evidence that, compared with no oral immunotherapy, peanut oral immunotherapy increases the risk and frequency of anaphylaxis (by around three times, from 7.1% without oral immunotherapy to 22.2% with oral immunotherapy), epinephrine use (by around two times, from 3.7% without to 8.2% with), and serious adverse events (by around two times, from 6.2% without to 11.9% with) to a similar extent during build-up and maintenance. Allergic reactions involving the gastrointestinal tract (vomiting, abdominal pain, mouth itching), skin and mucous membranes (hives or urticaria and swelling or angioedema), nose (congestion or rhinitis), and lungs (wheeze or asthma) also increased.

However, they found that quality of life was no better in people receiving oral immunotherapy compared to those that did not. The authors note that this is in contrast to observational studies, and this may be due to those studies not being controlled for confounding and bias. They note that large, well done randomised controlled trials are required to clarify the effect, if any, of peanut oral immunotherapy on quality of life.

In future research, it will be important to clarify patient values and preferences regarding food allergy therapies in general – understanding what patients expect from treatment, and what outcomes are desirable and undesirable. The measures to estimate health benefits and harms of food allergy interventions should be patient-centred outcomes, such as a risk and rate of allergic and anaphylactic reactions over time, as recommended by GRADE, the US National Institute of Allergy and Infectious Diseases, the FDA (Food and Drug Administration), and other organisations.

“Considering the current view of peanut allergy oral immunotherapy as a model for other food allergies, and the increasing global prevalence of food allergies, these findings are significant and important to the ongoing development of food allergy treatments,” concludes Dr Chu.

*Chu KD, Wood RA, French S, et al. Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety. Published: April 25, 2019. DOI:10.1016/S0140-6736(19)30420-9