Interferon beta-1b (Betaseron) was licensed on 7/23/93 for use in reducing the frequency of clinical exacerbations of relapsing-remitting multiple sclerosis with ambulatory patients. In clinical trials conducted prior to licensure, Betaseron was associated with an 85% incidence of injection site reactions in the treatment group of 147 patients. The subset of these reactions that included inflammation, pain, hypersensitivity, necrosis, and other non-specified symptoms was reported as significant (p<0.05) when compared to a 37% incidence of injection site reactions the placebo group of 123 patients. This and supplemental clinical trial data concerning injection site reactions are included in the current labeling for Betaseron, dated 7/28/93. Thus, by definition, injection site reactions are """"""""expected"""""""" events. FDA believes, however, that certain injection site reactions (e.g. spread by extension, induced vasculitis, required skin grafts, remained unresolved for months) may be """"""""unexpected"""""""", defined as """"""""symptomatically and pathophysiologically related to (expected events) but...of greater severity or specificity"""""""" and may be of particular clinical significance with possible negative clinical consequences. Accordingly, FDA believes that the injection site reaction reports should be evaluated for clinical course commonalities and possible pathophysiological mechanism(s). Any such suggestions might warrant further investigation and/or labelling changes (e.g. revised WARNINGS, contraindications) for continued safe and efficacious use of Betaseron. Therefore, a retrospective review of the injection site reaction reports for Betaseron since licensure is in progress.
