Unanswered questions and warnings involving anti-immunoglobulin E therapy based on 2-year observation of clinical experience.

The relatively rapid development and deployment of a clinically useful monoclonal antibody omalizumab has produced a number of questions still not answered despite massive research and many clinical trials. The mechanism of action as down-regulation of FceR1 receptors in the presence of low free immunoglobulin E (IgE) is incomplete. Some severe allergic asthmatic patients respond almost immediately, others take months, and some never respond. No accounting for the possible antigen sweeping by the complexes of IgG-IgE has been reported. Skin tests may remain positive for much longer than reported, raising the possibility of anaphylaxis with concomitant specific immunotherapy. Two cases of anaphylaxis to specific immunotherapy while being "covered" with anti-IgE are reported. Total IgE levels do not always rise as expected, six cases of static IgE levels in responders are reported. Total IgE levels do not dependably predict usefulness. Current guidelines for anti-IgE use in asthmatic patients may require reexamination as data from broad clinical experience are gathered.