A randomized double-blind, placebo-controlled study to assess the effects of omalizumab (humanized monoclonal anti-IgE antibody) on the early- and late-phase skin reactions and cellular infiltrate after multiple intradermal allergen challenges

Abstract

Rationale Immunoglobulin E probably plays a key role in early- and late phase- allergic cutaneous reactions (EPR and LPR) as well as the accompanying cellular influx. The aim of the study was to examine the effect of omalizumab on the EPR and LPR, as well as cellular infiltration, using a 14 day repeated skin allergen challenge design. Method Twenty-four allergic volunteers were randomized to receive either omalizumab at a dose of 0.016 mg/kg/IgE (IU/L)/4 weeks or placebo for a period of 12 weeks. On nine occasions, paired intradermal challenges of allergen (30 biological units) and diluent control were administered into the forearm at 2 weekly intervals. Cutaneous reactions were recorded 15 min and 6 hr after challenge and paired skin biopsies performed at 6 hr on weeks 0, 2, 4, 8 and 14 and studied by immunohistochemistry. Results Compared to placebo, omalizumab treated patients had a progressive reduction of both the EPR and the LPR. The LPR was significantly reduced within 2 weeks (p=0.012) and the EPR within 8 weeks (p=0.0093) of commencing treatment. Placebo patients showed a significant increase in cutaneous CD3+ T cells (p=0.016) after 14 weeks and this was paralleled by an increase in allergen-induced skin eosinophilia (p=0.05). These changes were not observed in the omalizumab group where CD3+ T cells (p=0.046) and eosinophils (p=0.019) were significantly lower compared to placebo. Conclusion Omalizumab reduces allergen-induced LPRs more rapidly than EPRs and appears to ameliorate the baseline T cell and allergen-induced eosinophil “priming” response in this multiple cutaneous allergen challenge model.