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

2017; Wiley; Volume: 48; Issue: 2 Linguagem: Inglês

10.1111/cea.13066

1365-2222

Lukas Jörg, Tatjana Pecaric-Petkovic, Stephan Reichenbach, Michael Coslovsky, Odile Stalder, Werner J. Pichler, Oliver Hausmann,

Mast cells and histamine

Summary Background Omalizumab has been shown to be effective in treating chronic spontaneous urticaria ( CSU ). The reduction in Fcε 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 . Methods Thirty patients were randomized in a 2:1 ratio to receive either 300 mg omalizumab or placebo. Four monthly applications of omalizumab/placebo were followed up with a visit 2 months after the last injection. The primary endpoint was the Fcε RI receptor density change on basophils. Results Omalizumab led to a significant reduction in Fcε RI receptor density on basophils as soon as 1 week after the first injection: baseline omalizumab vs placebo group, 80.31 ± 47.18 × 10³ vs 78.29 ± 45.09 × 10³ receptors/basophil ± SD ; 1 week, 72.89 ± 47.79 × 10³ vs 27.83 ± 20.87 × 10³, P = .001. This effect continued during the treatment phase and persisted for 2 months after the last injection: 93.81 ± 56.50 × 10³ vs 21.09 ± 15.23 × 10³, 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 , CD 63 10.75% (7.35) in the placebo group vs 8.35% (15.20) in the omalizumab group, P = .778. Conclusion We demonstrated a rapid reduction of Fcε RI receptor density on basophils following treatment with omalizumab. Because CU ‐ BAT using well‐characterized, omalizumab‐naïve 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, Fcε RI density and CU ‐ BAT might be promising cellular‐based assays.