AbstractBackgroundFollowing 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).MethodThis 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.ResultsThe 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.ConclusionIn our experience, 98.4% of 258 RDDs to biologics were successfully completed; RDD was safe and effective for our population.