A New Pediatric Protocol for Rapid Desensitization to Monoclonal Antibodies

Abstract

Monoclonal antibodies are important therapeutic tools, but their usefulness may be limited when patients experience acute hypersensitivity reactions. Patients reporting a history of adverse allergic reaction are likely to discontinue their therapeutic protocol or be switched to an alternative drug, which is sometimes less effective than that originally prescribed. Drug desensitization has proven to be a highly effective strategy to readminister a drug in a patient who has experienced a hypersensitivity reaction. It involves forcing the patient's immune system to accept and tolerate the allergen. Nevertheless, such a procedure is still empiric for monoclonal antibodies and not common in the pediatric population. The aim of our study is to demonstrate the clinical success of a new protocol of rapid desensitization to infliximab in a pediatric patient affected by ulcerative colitis, who developed an anaphylaxis to the drug. We used a protocol of rapid desensitization consisting of 13 steps, with the first being 1/1,000,000 of the cumulative and total dose. Such a protocol has proven to be able to induce a temporary tolerance to infliximab, allowing the patient to achieve complete control of his disease.

Hypersensitivity Reactions to Monoclonal Antibodies in Children

“…Basophil activation test (BAT) is measured by using mAbs to the specific activation markers CD63 and CD203c. So far BAT is used for research purpose only in case of immediate reactions [102,103]. In a pediatric study, infliximab hypersensitivity has been studied with BAT procedure at a drug concentration of 10 mg/mL with three different dilutions: 1:5; 1:125 and 1:125 [103].…”

“…So far BAT is used for research purpose only in case of immediate reactions [102,103]. In a pediatric study, infliximab hypersensitivity has been studied with BAT procedure at a drug concentration of 10 mg/mL with three different dilutions: 1:5; 1:125 and 1:125 [103]. In the acute phase, serum tryptase level are of paramount importance and very informative.…”

Rituximab Desensitization in Pediatric Patients: Results of a Case Series

“…This is in contrast with other studies, in which adult subjects experience HSR upon first exposure, 1,4 and consistent with one of the pediatric case reports. 5 It is possible that reactions upon reexposure may be more common in younger patients.…”

“…This protocol started at a lower dose than the protocol we described for rituximab (1/1,000,000 compared with our 1/100,000) and tripled the dose in each step instead of doubling the dose. 5 In general, it is preferable that the dose increase for each step of desensitization is no more than a 2-fold increase. 7 Our protocol not only adheres to this concept but also addresses a new concept of adjusting the rate of infusion during desensitization for the patient's weight, which is particularly helpful in younger patients.…”

“…While HSRs and desensitization to mAbs have been well described in adults, [1][2][3] to our knowledge, the experience in children is limited to only two case reports, including only one to rituximab. 5,6 We discuss HSRs and rapid desensitization to rituximab in a tertiary care pediatric center, including reaction evaluation, pretreatment regimens, a successful desensitization protocol, and outcomes. To our knowledge, this is the first report of a series of mAb desensitizations in a pediatric population.…”