Effect of ketotifen premedication on adverse reactions during peanut oral immunotherapy

Abstract

BackgroundOral immunotherapy (OIT) has shown promise in inducing desensitization for food allergy. However, there are safety concerns regarding the frequency and severity of adverse events during food OIT.ObjectiveTo evaluate the effect of Ketotifen premedication on adverse reactions during peanut OIT.MethodsA randomized single blind placebo controlled pilot study was performed. Peanut OIT was performed using a previously published protocol. Ketotifen was up-titrated to 2 mg twice daily over two weeks (week -2 to 0), followed by a peanut OIT initial escalation day (day 1). Ketotifen was administered from week 0–4 of peanut OIT; reactions to peanut OIT doses were recorded by clinic staff and subject diary.ResultsSix subjects (median age 10 years, peanut IgE >100kUA/L) were enrolled, 4 randomized to Ketotifen, 2 to placebo. The most common side effect of Ketotifen was fatigue (9% during up-titration). The rate of reaction per peanut OIT dose was lower for subjects on ketotifen (K) compared to placebo (P) during initial escalation on day 1 (K: 22% (8/36) vs. P: 67% (12/18)); week 0–4 build-up doses (K: 75% (3/4) vs. P: 100% (2/2)); and week 0–4 home doses (K: 50% (54/108) vs. P: 82% (27/33)). The rate of gastrointestinal symptoms per peanut OIT dose was also lower for subjects on ketotifen during initial escalation on day 1 (K: 17% (6/36) vs. P: 61% (11/18)); week 0–4 build-up doses (K: 75% (3/4) vs P: 100% (2/2)); and week 0–4 home doses (K: 46% (50/108) vs. P: 82% (27/33)).ConclusionsKetotifen premedication is well tolerated and reduces the rate of gastrointestinal symptoms during peanut OIT. These findings require confirmation in a larger study of Ketotifen premedication used throughout peanut OIT.Trial registrationClinical Trials number: NCT0162515

Peanut gastrointestinal delivery oral immunotherapy in adolescents: Results of the build‐up phase of a randomized, double‐blind, placebo‐controlled trial (PITA study)

“…Finally, ingesting capsules also avoids aversion, which is commonly encountered in peanut allergy. To our knowledge, using sealed peanut capsules has been tested in only one study on a small number of patients without placebo controls …”

“…To our knowledge, using sealed peanut capsules has been tested in only one study on a small number of patients without placebo controls. 37 Efficacy was assessed on the basis of the increase in the reactiv- and ED 50 between 100 and 200 mg of pp. 38 Other authors indicated in 2016 that there was no significant difference between quantifying EDs in real life and upon food challenge.…”

Oral Immunotherapy for Food Allergy

“…In 2013, a randomized single-blind placebo-controlled study of 6 patients undergoing peanut OIT showed that premedication with ketotifen at 2 mg twice daily might reduce the incidence of gastrointestinal symptoms during active OIT [73]. Furthermore, Takahashi et al [74] studied the use of montelukast with OIT in a retrospective study of 5 children, where leukotriene receptor antagonists appeared to help patients reach their target dose.…”

“…Case reports and small open-label trials have been conducted with a number of other adjunctive therapies, including interferon gamma, ketotifen, and leukotriene receptor antagonists [71][72][73][74][75]. In 2013, a randomized single-blind placebo-controlled study of 6 patients undergoing peanut OIT showed that premedication with ketotifen at 2 mg twice daily might reduce the incidence of gastrointestinal symptoms during active OIT [73].…”

The Use of Omalizumab in Food Oral Immunotherapy

“…Efforts to improve safety and, therefore, efficacy of OIT have included the use of anti-histamines, such as cetirizine (Lafuente et al 2014;Meglio et al 2004), mast cell stabilizers, such as ketotifen (Jagdis et al 2014), or the leukotriene receptor antagonist montelukast (Takahashi et al 2014), with the modest success. More recently, the anti-IgE molecule omalizumab has been used to accelerate OIT desensitization in high-risk patients and to improve the safety profile of this procedure.…”