Hypersensitivity reactions to tocilizumab: role of skin tests in diagnosis.

Hypersensitivity reactions to tocilizumab: role of skin tests in diagnosis SIR, Tocilizumab (TCZ) is a humanized anti-human IL-6 receptor (IL-6R) monoclonal antibody that binds to circulating soluble IL-6R and membrane-expressed IL-6R. This inhibits IL-6 binding to both forms of IL-6R and blocks the pro-inflammatory effects of IL-6 [1]. TCZ is approved in Europe and the USA for the treatment of moderate to severe RA in adult patients who have responded inadequately or been intolerant to previous therapy with one or more DMARDs or TNF inhibitors [1]. The most common adverse reactions to TCZ are infections and gastrointes-tinal symptoms [2]. However, increased therapeutic use of this monoclonal antibody in RA has disclosed other side effects. Recently, delayed hypersensitivity reactions to TCZ have been described. These were analysed by means of skin biopsies, showing CD4 + T cells as well as eosinophil infiltration in the upper dermis [3, 4]. Among hypersensi-tivity reactions, anaphylaxis has also been reported [5]. Thus it is important to define simple and reliable diagnostic tests for patients who have experienced hypersensitiv-ity reactions to TCZ. Our aims were to analyse the frequency of hypersensitivity reactions in patients treated with TCZ and to evaluate the role of skin tests in the diagnosis. In the Clinical Immunology and Rheumatology Units of Pisa University, 72 patients were treated with TCZ during 2005–13. Among them, we studied five patients [four females, one male; mean age 50 years (S.D. 10.79, range 31–62)] with hypersensitivity reactions to TCZ defined as previously reported [6]. Written consent was obtained from the patients according to the Declaration of Helsinki. The Ethics Committee of the University Hospital, Pisa approved the study. Commercial TCZ was used for skin prick tests (SPTs) (0.2, 2 and 20 mg/ml) and intradermal tests (IDTs) (0.002, 0.02, 0.2, 2 and 20 mg/ml). These concentrations were found to be non-irritant in 10 healthy subjects. A wheal area 53 mm was considered positive compared with the negative control (saline solution). Histamine was used as a positive control. SPT results were evaluated after 15 min and IDT after 20 min. Anti-histamine treatment was discontinued 5 days before testing and steroids 10 days. The patients were evaluated 15–72 months after the reaction. Among the 72 patients treated, 20 discontinued TCZ treatment: 7 for the development of side effects, 7 for inefficacy, 5 for hypersensitivity reactions and 1 for remission of the disease; 1 patient died for unrelated reason. Among …