Department of Rheumatology, Immunology and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Adverse Drug Reactions, Analysis and Consulting, ADR-AC GmbH, Bern, Switzerland.
Clin Exp Allergy. 2018 Feb;48(2):196-204. doi: 10.1111/cea.13066. Epub 2017 Dec 12.
Omalizumab has been shown to be effective in treating chronic spontaneous urticaria (CSU). The reduction in FcεRI 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.
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 FcεRI receptor density change on basophils.
Omalizumab led to a significant reduction in FcεRI 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, CD63 10.75% (7.35) in the placebo group vs 8.35% (15.20) in the omalizumab group, P = .778.
We demonstrated a rapid reduction of FcεRI 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, FcεRI density and CU-BAT might be promising cellular-based assays.
奥马珠单抗已被证明可有效治疗慢性自发性荨麻疹（CSU）。嗜碱性粒细胞和肥大细胞表面 FcεRI 受体密度的降低被认为在其疗效中起主要作用。我们进行了一项双盲、随机、安慰剂对照试验，以研究奥马珠单抗在抗组胺药物耐药性 CSU 患者中的作用机制。
30 名患者按 2:1 的比例随机分为奥马珠单抗或安慰剂组。接受 4 次奥马珠单抗/安慰剂每月一次的治疗，最后一次注射后 2 个月进行随访。主要终点是嗜碱性粒细胞 FcεRI 受体密度的变化。
奥马珠单抗治疗后可立即显著降低嗜碱性粒细胞 FcεRI 受体密度：基线奥马珠单抗组 vs 安慰剂组，80.31±47.18×10³ vs 78.29±45.09×10³受体/嗜碱性粒细胞±SD；1 周时，72.89±47.79×10³ vs 27.83±20.87×10³，P=0.001。这种作用在治疗期间持续，并在最后一次注射后 2 个月持续存在：93.81±56.50×10³ vs 21.09±15.23×10³，P=0.002。尽管进行了治疗，但患者血清对供体嗜碱性粒细胞的嗜碱性粒细胞“释放能力”和嗜碱性粒细胞激活试验（CU-BAT）的测定值没有变化：CU-BAT，安慰剂组 CD63 为 10.75%（7.35），奥马珠单抗组为 8.35%（15.20），P=0.778。
我们证实奥马珠单抗治疗后嗜碱性粒细胞 FcεRI 受体密度迅速降低。由于在治疗期间使用特征明确、奥马珠单抗未致敏的供体嗜碱性粒细胞的 CU-BAT 没有改变，自身反应性血清因子似乎保持不变。这表明奥马珠单抗对嗜碱性粒细胞具有细胞作用。为了预测奥马珠单抗的反应时间并监测疾病，FcεRI 密度和 CU-BAT 可能是有前途的基于细胞的检测方法。
