Double-blind placebo-controlled trial of the effect of omalizumab on basophils in chronic urticaria patients

BackgroundOmalizumab has been shown to be effective in treating chronic spontaneous urticaria (CSU). The reduction in Fc epsilon RI receptor density on the surface of basophils and mast cells is thought to play a major role in its effectiveness. We conducted a double-blind, randomized, placebo-controlled trial to investigate the mode of action of omalizumab in patients with antihistamine-resistant CSU. MethodsThirty patients were randomized in a 2:1 ratio to receive either 300mg omalizumab or placebo. Four monthly applications of omalizumab/placebo were followed up with a visit 2months after the last injection. The primary endpoint was the Fc epsilon RI receptor density change on basophils. ResultsOmalizumab led to a significant reduction in Fc epsilon RI receptor density on basophils as soon as 1week after the first injection: baseline omalizumab vs placebo group, 80.3147.18x10(3) vs 78.29 +/- 45.09x10(3) receptors/basophil +/- SD; 1week, 72.89 +/- 47.79x10(3) vs 27.83 +/- 20.87x10(3), P=.001. This effect continued during the treatment phase and persisted for 2months after the last injection: 93.81 +/- 56.50x10(3) vs 21.09 +/- 15.23x10(3), P=.002. Values for basophil releasability and the basophil activation test (CU-BAT) of patient serum using donor basophils were unchanged despite treatment: CU-BAT, CD63 10.75% (7.35) in the placebo group vs 8.35% (15.20) in the omalizumab group, P=.778. ConclusionWe demonstrated a rapid reduction of Fc epsilon RI receptor density on basophils following treatment with omalizumab. Because CU-BAT using well-characterized, omalizumab-naive donor basophils did not change during the treatment phase, autoreactive serum factors seem to remain unaltered. This points towards a cellular effect of omalizumab on basophils. To predict the omalizumab response time and to monitor disease, Fc epsilon RI density and CU-BAT might be promising cellular-based assays.