The Peanut Allergen immunotherapy, Clarifying the Evidence, or PACE, study found that existing peanut oral immunotherapy considerably increased allergic and anaphylactic reactions despite inducing desensitization.
Researchers wrote that the results demonstrate the need for safer food allergy treatment approaches and trials focused on patient-important outcomes.
“Randomized-controlled trials and meta-analyses support the safety and efficacy of sublingual and subcutaneous immunotherapy for these respiratory allergic conditions,” Derek K. Chu, MD, PhD, FRCPC, of the department of medicine at McMaster University and St. Joseph’s Healthcare Hamilton, Ontario, Canada, wrote. “In contrast, narrative reviews, observational studies, and a historical lack of randomized trials drive the debate on whether oral immunotherapy for food allergy is ready for routine and widespread clinical use, or whether it should remain an investigational therapy (ie, more research is needed).”
Researchers conducted a systematic review and meta-analysis that involved a search of multiple databases to find published and unpublished randomized-control trials that compared oral immunotherapy to placebo or allergen avoidance for treatment of peanut allergy. Main outcomes, meta-analyzed by random effects, were anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life.
The analysis included 16 reports of 12 randomized-control trials from the U.S., U.K., Europe and Australia. Across the trials, 1,041 patients with a median age of 8.7 years (IQR, 5.9-11.2) were enrolled.
Researchers found that when compared with no oral immunotherapy, oral immunotherapy increased anaphylaxis risk (RR = 3.12 [95% CI, 1.76-5.55]; I² = 0%; risk difference [RD] = 15.1%; high-certainty), anaphylaxis frequency (incidence rate ratio = 2.72 [95% CI, 1.57-4.72]; I²= 0%; RD =12.2%; high-certainty) and epinephrine use (RR = 2.21 [95% CI, 1.27-3.83]; I²= 0%; RD = 4.5%; high-certainty) without a significant difference in buildup and maintenance.
Oral immunotherapy increased serious adverse events (RR = 1.92 [95% CI, 1-3.66]; I²=0%; RD = 5.7%; moderate-certainty) and non-anaphylactic reactions such as vomiting, angioedema, upper tract respiratory reactions and lower tract respiratory infections. Patients who received oral immunotherapy did not have a better quality of life compared to those who did not.
Researchers noted that although the study included all available evidence, they were limited by the small number of participants. They also noted that further investigation is needed to determine if longer term oral immunotherapy or treatment has a different efficacy and safety profile in adults.
“Chu and colleagues have used the more patient-centered endpoint of peanut-induced anaphylaxis, either as a result of unplanned exposure to peanuts or as a result of the daily doses of peanuts in the oral immunotherapy,” Graham Roberts, DM, MRCPCH, MA, MSc, and Elizabeth Angier, MSc, of the University of Southampton, U.K., wrote in a related comment. “The endpoint arguably provides a much better summary of a patient’s experience in day-to-day living than one oral peanut challenge.”– by Erin Michael
Disclosures: Chu reports being an investigator on an ongoing peanut oral immunotherapy trial (NCT01601522) funded by a federal body (AllerGen NCE through Government of Canada) and was blinded to the study. Please see study for all other authors’ relevant financial disclosures.