D3.26 - Anaphylaxis associated with biosimilar Tocilizumab: in vitro and in vivo diagnosis
Case report
Biosimilar drugs are biological medicines equivalent in molecular structure, pharmacological activity, efficacy, and safety to another biological medicine, referred to as the reference drug, authorized within the European Economic Area (EEA).
In the case of tocilizumab, the first biosimilar was approved in Europe in 2023.Tocilizumab is a humanized recombinant monoclonal antibody of immunoglobulin G1 (IgG1) that binds to the soluble interleukin-6 receptor, blocking the pro-inflammatory activities of IL-6.It has demonstrated good efficacy and safety in many rheumatic diseases. Initially approved in 2010 for use in rheumatoid arthritis (RA).
Reports of hypersensitivity reactions to biosimilar versions of these drugs are rare. We present a case and its diagnosis using in vivo techniques (prick test and intradermal test) and in vitro techniques (basophil activation test).
The concentrations at which we performed the tests for both the biosimilar version and the reference version were: Prick test 2mg/mL, 20 mg/mL; intradermal: 2mg/mL and 20 mg/mL.
A 61-year-old patient was diagnosed with an overlap syndrome (SLE, RA, and Sjögren’s syndrome) in 2004. In 2012, she began treatment with intravenous tocilizumab. She continued receiving this treatment without incidents from 2018 to 2024.
In July 2024, she received her first dose of biosimilar tocilizumab. During the second administration, 5–10 minutes after the infusion started, she developed hives, pruritus on the scalp, ears, palms, and soles, shortness of breath, wheezing, and epigastric pain. A tryptase sample confirmed anaphylaxis due to elevated levels.
Four weeks after the reaction, skin tests were conducted. The prick test was positive for the biosimilar tocilizumab implicated in the reaction. In contrast, both the prick test and intradermal test were entirely negative for the reference intravenous tocilizumab.A basophil activation test was also performed to compare the two drugs, which was positive for the biosimilar and negative for the reference drug. Finally, a controlled drug challenge was performed with the reference drug not implicated in the reaction, and it yielded negative results.
These findings confirmed a type I hypersensitivity reaction to the biosimilar drug through in vitro and in vivo testing, with good tolerance to the reference drug.
