Oral Immunotherapy for Peanut Allergy (PACE): A Systematic Review and Meta–analysis of Efficacy and Safety

Abstract

To systematically review the efficacy and safety of peanut oral immunotherapy (OIT) compared with allergen avoidance or placebo OIT for peanut allergy.The population included individuals with peanut allergy (61% male, 39% female), the majority of whom were children (median age: 8.7 years; interquartile range [IQR]: 5.9–11.2 years) participating in peanut OIT trials in North America, Australia, and Western Europe.This systematic review and meta-analysis included a comprehensive search of international health care databases from the United States, Latin America, Europe, and China through December 2018. Authors performed searches for randomized controlled trials comparing peanut OIT to no OIT for the treatment of peanut allergy. The authors screened studies, extracted data, assessed risk of bias, and assessed quality of evidence by the Grading of Recommendations Assessment, Development, and Evaluation approach. The main outcomes included treatment efficacy (ie, proportion of patients passing an oral food challenge), anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life.Twelve randomized controlled trials were included, with 1041 participants in total undergoing peanut OIT for a median follow-up of 1.0 year (IQR: 0.8–1.4), achieving a median target dose of 2000 mg of peanut protein (IQR: 375–4000). Passing a supervised, in-clinic oral food challenge was more likely in the OIT group. Subjects undergoing peanut OIT had increased anaphylaxis risk (risk ratio: 3.12 [95% confidence interval (CI): 1.76–5.55]), anaphylaxis frequency (incidence rate ratio: 2.72 [95% CI: 1.57–4.72]), and epinephrine use (risk ratio: 2.21 [95% CI: 1.27–3.83]). Peanut OIT increased serious adverse events and nonanaphylactic reactions. These findings were irrespective of OIT protocol, proprietary formulation or not, and phase of OIT (build-up versus maintenance). Quality of life was not different between groups.High-quality evidence shows that current peanut OIT regimens effectively achieve a modest level of desensitization but clinically result in a net increase in anaphylaxis and other allergic reactions compared with avoidance or placebo, rather than preventing them, as intended. These data support the need for improved food allergy treatment approaches with an enhanced safety profile.Hesitancy to implement OIT in routine clinical practice centers around concerns for safety, standardization of approach, practicality of long-term therapy maintenance, and identification of patients who will respond best with the fewest side effects. Although most adverse effects from OIT are mild and do not prevent patients from continuing therapy, the potential for life-threatening anaphylaxis exists. Despite the safety concerns outlined in this report, OIT is being offered in some clinical practices and is expected be available on a larger scale in the near future. It is important to remember that OIT may not be the best fit for many food-allergic patients, and as we near the likely acceptance of a US Food and Drug Administration–approved peanut OIT product, patients will seek advice from their pediatrician before talking to an allergist to help them navigate the pros and cons of interventional therapy versus the traditional approach of maintaining strict allergen avoidance. Salient points for the pediatrician to remember include the following. (1) OIT and all other products currently under investigation for treatment of food allergy provide benefit while on therapy but do not appear to induce sustained remission for the majority of allergic patients. (2) There are no surrogate biomarkers to identify which patients will receive the greatest benefit with the fewest side effects. (3) Anaphylaxis while on therapy is a potential side effect, and patients must continue to carry autoinjectable epinephrine at all times. Shared decision-making and an open and honest discussion with families considering therapeutic options are necessary in providing comprehensive care of our patients with food allergy and their families.