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Peanut desensitization comes at cost of anaphylaxis

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“The key criticism of this systematic review is inherent in its method because studies with different designs were grouped together,” Graham Roberts, MD, and Elizabeth Angier, MD, wrote in an accompanying editorial. In addition, the studies chosen did not account for the development of long-term peanut tolerance after the therapy was discontinued.

Also, the researchers did not factor in the variation in patterns of anaphylactic events, with patients in the treatment groups having events at home in conjunction with daily peanut doses, while the control patients would have had events mainly away from home.

“Unfortunately, the trials have not provided information about which participants benefited most from the intervention,” they wrote.

“Trading treatment-related side effects at home for allergic reactions to accidental exposures out of the house [i.e., in social situations] might beneficial for some patients,” they added. However, more research is needed to determine which patients would benefit from different treatment options at home and outside the home. The less effective but safer option of epicutaneous immunotherapy might be preferred by some patients. And early introduction of peanut products during infancy may prevent many cases of peanut allergy.

Dr. Roberts and Dr. Angier are at the University of Southampton (England). Both are members of the European Academy of Allergy and Clinical Immunology Allergen Immunotherapy Guidelines Group, which has recently published guidelines on immunotherapy. They wrote an editorial to accompany the article by Chu et al (Lancet. 2019 June 1;393:2180-1). They had no financial conflicts to disclose.



Oral immunotherapy reduced sensitivity to peanuts in allergic individuals, but at the cost of increased risk of anaphylaxis and other reactions, based on a meta-analysis from more than 1,000 patients published in the Lancet.

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In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, Derek K. Chu, MD, of McMaster University, Hamilton, Ont., and colleagues reviewed 12 trials conducted between 2011 and 2018 with a total of 1,041 patients (median age, 9 years).

Overall, the risk of anaphylaxis was significantly higher among children who received oral immunotherapy, compared with no therapy (risk ratio, 3.12) as was anaphylaxis frequency (incidence rate ratio, 2.72) and use of epinephrine (RR, 2.21).

In addition, oral immunotherapy increased serious adverse events, compared with no therapy (RR, 1.92). Nonanaphylactic reactions also went up among oral immunotherapy patients, with increased risk for vomiting (RR, 1.79), angioedema (RR, 2.25), upper respiratory tract reactions (RR, 1.36), and lower respiratory tract infections (RR, 1.55).

Quality of life scores were not significantly different between patients who did and did not receive oral immunotherapy, the researchers noted.

The oral immunotherapy consisted of defatted, lightly roasted peanut flour in 10 studies, and a combination of peanut paste, peanut extract, or ground and defatted peanut in the other studies.

The oral immunotherapy did induce desensitization to peanuts in support of earlier studies including the subcutaneous immunotherapy trial, but “this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis,” Dr. Chu and associates wrote.

However, “rather than take the view that these data denounce current research in oral immunotherapy as not successful, we instead suggest that this research has reached an important milestone in mechanistic but not clinical efficacy. From a clinical or biological perspective, the apparently paradoxical desensitization versus longitudinal clinical findings show the lability and unreliability of allergen thresholds identified during oral food challenges because patients often unpredictably reacted to previously tolerated doses outside of clinic,” they emphasized.

The findings were limited by several factors including the small sample size, compared with similar studies for asthma or cardiovascular conditions, and by incomplete or inconsistent data reporting, the researchers noted. However, the results are the most comprehensive to date, and support the need for food allergy treatments with better safety profiles, using peanut allergy immunotherapy as a model for other food allergies.

Dr. Chu and two other authors reported being investigators on a federally funded ongoing peanut oral immunotherapy trial. Two authors reported receiving a variety of grants from organizations such as the National Institutes of Health; the American Academy of Allergy, Asthma, & Immunology; or pharmaceutical companies.

SOURCE: Chu DK et al. Lancet. 2019 June 1;393:2222-32.

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