Infliximab-graded challenge in a patient with Crohn’s disease and adalimumab hypersensitivity

Abstract

Background: Infliximab and adalimumab are monoclonal antibodies to tumor necrosis factor alpha (TNF-alpha) used in the treatment of Crohn's and other inflamatory diseases. Infliximab is a chimeric monoclonal antibody administered via infusion, while adalimumab is a humanized monoclonal antibody administered by subcutaneous injection. Infliximab has been postulated to be more immunogenic as it is not entirely humanized. While there are multiple reports of adalimumab treatment in patients after an adverse reaction to infliximab, there is a paucity of literature reporting the converse -treatment with infliximab after adverse reaction to adalimumab. Thus, it is difficult to estimate the risk of cross-sensitization. Graded drug challenges are often utilized for patients unlikely to be allergic to a specific drug, but where there is still significant concern for a reaction. Objective: To present a patient with Crohn's disease and a history of systemic hypersensitivity to adalimumabwho successfully underwent a graded intravenous challenge with infliximab. Methods: The patient had a prior history of generalized urticaria that occurred after her third dose of adalimumab. Intradermal skin tests with 1:100, 1:10, and full strength adalimumab were positive. She continued to have very active inflammatory bowel disease, for which her gastroenterologist preferred to treat with an anti-TNF agent. Infliximab was the chosen alternative anti-TNF agent. Consequently, she underwent an infliximab-graded challenge of 3 doses over 5 hours in an outpatient clinic staffed by trained allergists. She received 5 mg over 30 minutes, followed by 20 mg over 1 hour, then 75 mg over 1 hour. Between doses, the infusionwas held for 30 minutes to assess for adverse effects. Results: The patient received 100 mg of intravenous infliximab during the graded challenge. The patient did not experience any immediate or delayed adverse reactions. Conclusions: This is the first case, to our knowledge, to demonstrate a successful infliximab-graded challenge for a patient with a prior hypersensitivity reaction to adalimumab. For patients who require TNF-alpha inhibitors, but with previous reactions and concern for cross-sensitization, a graded challenge with the first dose of an alternate agent, under observation by care providers trained to manage adverse drug reactions, may be a safe approach.