Following the increased use of biological agents, a subset of patients experiences hypersensitivity reaction (HSR). We reported our experience with rapid drug desensitization (RDD) to nine biologics (rituximab, infliximab, cetuximab, trastuzumab, pertuzumab, nivolumab, brentuximab, tocilizumab and filgrastim) and identified risk factors for breakthrough reactions (BTRs). This was a retrospective review (2013-2022) of patients with immediate HSRs to biological agents. Initial HSRs were classified as grade 1, 2, or 3 in their severity. Skin prick tests (SPT)/intradermal tests (IDT) were performed using implicated agents. The phenotypes of HSRs were defined as Type I, cytokine-release syndrome (CRS), mixed reactions (cytokine-release + type I) based on history, clinical presentations and skin tests with implicated biologicals. A 12-step RDD protocol was used. The study comprised 45 patients (F/M: 31/14, median age: 55 (range: 20-69)). Majority of the patients reacted at the first infusion (n: 29/45, 64.4%). The majority of initial HSRs were grade 3 (n: 24/45, 53.3%) and grade 2 (n: 21/45, 46.6%); none were grade 1. Initial reactions were presented as type I (n: 20/45, 44.4%), CRS (n: 12/45, 26.6%) and mixed (n: 13/45, 28.8%). A total of 258 RDDs were performed and 98.4% of them were completed successfully. BTRs occurred in 36/258 (13.9%) infusions of RDDs. There was no significant association between the BTRs and age, drug cycle, SPT and IDT positivity, gender, comorbidities, or atopy. In our experience, 98.4% of 258 RDDs to biologics were successfully completed; RDD was safe and effective for our population.
International archives of allergy and immunology •
Rapid drug desensitization (RDD) induces a temporary tolerance to biologics which induce hypersensitivity reactions (HSRs). Data are limited regarding the use of RDD outside the USA. Our purpose was to report our data on RDD to rituximab, infliximab, cetuximab, and trastuzumab. The study was conducted as a retrospective chart review of patients with symptoms of HSRs to biologics. HSRs were classified as grades I, II, and III, based on their severity. Skin-prick tests/intradermal tests (IDTs) were performed with the implicated biologics. The 12-step RDD protocol was used. The study group comprised 11 women and 6 men (mean age: 47 ± 11.7 years). Fourteen patients experienced HSRs to rituximab; 3 had HSRs to cetuximab, infliximab, and trastuzumab, respectively. HSRs to cetuximab, infliximab, and trastuzumab occurred during the first infusion and were all grade III. Twelve of the 14 patients with rituximab hypersensitivity had a reaction during the first infusion; 10 patients had grade II reactions and 4 had grade III reactions. Respiratory symptoms were the most frequent presentation of HSR. Skin tests with rituximab were performed on 10 patients; only 3 resulted in positive IDTs (with 1:100 dilutions) and the other tests were negative as were those performed with the other biologics. Of 96 RDDs, 89 desensitizations were performed with rituximab, 5 with cetuximab, 1 with infliximab, and 1 with trastuzumab. There were 12 (13.5%) breakthrough reactions, all of which were associated with rituximab and were less severe than the initial reactions. RDD was found to be safe and effective in the largest case series of RDDs with biologics in our country, Turkey.
