Peanut Oral Immunotherapy With or Without H₁ and H₂ Antihistamine Premedication for Peanut Allergy (PISCES): A Placebo-Controlled Randomized Clinical Trial

Peanut oral immunotherapy (OIT) has been associated with an increase in adverse events such as anaphylaxis, nausea or vomiting, wheezing, and abdominal pain. This study aims to determine if premedication with H₁ and H₂ blockers can mitigate these side effects and improve patient quality of life.

Forty three patients with a history of peanut allergy were enrolled in Hamilton Health Sciences’ McMaster Children’s Hospital in Canada. Peanut allergy was confirmed by clinical symptoms, positive skin testing, and positive peanut-specific serum IgE. Patients with a history of severe uncontrolled asthma and chronic urticaria were excluded from the study.

This study was a double-blinded randomized control trial. Patients were randomized to 3 treatment arms: peanut OIT + H₁ and H₂ antihistamines, peanut OIT + placebo antihistamines, and placebo OIT + placebo antihistamines. Patients in the antihistamine treatment group received 2.5 mg desloratadine daily and ranitidine 75 mg twice a day. Each group had up-titration of their OIT every 2 weeks in-person until they reached 500 mg of peanut protein daily then were maintained on that dose for 12 months. The primary outcome was the incidence of adverse reactions, and the secondary outcome measure was quality of life (QoL) assessment using the Food Allergy Quality of Life Questionnaire.

The mean age was 7.8 years old with 35% female participants. The 3 groups had similar baseline skin prick testing, peanut IgE, eliciting peanut dose and quality of life measures. The risk of having any adverse reaction or multiple adverse reactions did not differ between OIT + antihistamine group versus OIT + placebo group. The risk of moderate or severe adverse events was reduced in the OIT+ antihistamine group compared with OIT + placebo (1.9 vs 4.2 events per patient, incidence rate ratio 0.46 [0.24–0.89]) primarily from a reduction in urticarial events. However, premedication with antihistamines increased the incidence of tiredness and dizziness and did not significantly improve QoL scores compared with OIT + placebo group.

Overall, pretreatment with antihistamines while on peanut OIT reduced the incidence of moderate to severe adverse events but not the number of adverse events patients experienced. However, patients treated with antihistamines experienced a higher incidence of neuropsychiatric side effects such as fatigue and did not have increased QoL.

Peanut OIT has been effective at desensitizing peanut-allergic patients; however, adverse events associated with OIT can lead patients to stop therapy. This study is the first randomized control trial looking at antihistamine premedication in patients on peanut OIT. The results suggest that pretreatment with antihistamines shows some benefit in reducing moderate adverse events with OIT but not without their own side effects. Overall, there was no notable increase in QoL. Follow-up studies should be done with a larger sample size. Additional therapies such as biologics are also being evaluated in their role in mitigating side effects associated with OIT.