Abstract
BACKGROUND: Spontaneous reporting of adverse drug reactions (ADR) to biological agents used for cancer and immuno-mediated disease treatment is important for furthering knowledge regarding the safety of these new drugs. An analysis was carried out in Italy on reports of anaphylaxis caused by biological agents. METHODS: Data were extracted from the national Spontaneous Reporting Database. Since biological drugs refer to different ATC (Anatomical Therapeutic Classification) codes, in this study they have been extracted by the presence of "mab" and/or "cept" suffixes. Cases were defined as following: A) reports with the string “anaph” in the description of the event or in the WHO-ART (Adverse Reactions Terminology) coded preferred terms; B) reports with adverse reactions referring to at least 2 of selected System Organ Classes (skin, respiratory, cardiovascular and gastrointestinal disorders) with an onset within 24 hours after administration. All selected cases were reviewed and the case definition from the "Second Symposium on the Definition and Management of Anaphylaxis" was applied to evaluate the reports (JACI 2005;115(3):584–591). RESULTS: The Italian database up to March 2011 contains 3820 reports related to biologicals. According to selection criteria, a total of 334 reports were extracted: 65 for group A and 269 for group B. By application of the anaphylaxis case definition, 2 cases belonging to group A and 139 to group B were excluded after individual review. Out of 193 reports meeting the case definition, 8 (4.1%) were reported in children and adolescents up to 18 years of age. The most reported responsible drugs were infliximab with 83 (43%) cases, followed by cetuximab (41–21%) and rituximab (28–14%); other 11 different biologicals were associated with the remaining 32 cases (22%), with up to 8 reports each. CONCLUSIONS: Spontaneous reporting is an important source to provide further knowledge on the reactogenicity of biological agents. Three-fourths of Italian reports of anaphylaxis concern 3 chimaeric antibodies containing a murine component. In our study, the best identification of cases of anaphylactic reactions came out of the combination of selected reported terms, application of case definition and expert review of individual reports.