我叫 Martin Metz。我是皮肤病学和过敏学教授，同时担任德国柏林夏里特医学院过敏学研究所副主任。我深感荣幸，能在欧洲皮肤病与性病学会（EADV）会议上报告一些新数据，其中最令人振奋的成果之一被选为口头最新突破性报告，内容聚焦瑞米布替尼（Remibrutinib）治疗慢性自发性荨麻疹（CSU）的疗效。
瑞米布替尼是一种 BTK 抑制剂，此前已有研究证实其效果，我们也发表过相关成果 —— 在 CSU 治疗领域，它是一种非常有效的药物，对 CSU 患者确实能起到治疗作用。我们此次研究则更深入探究了与肥大细胞无直接关联、而是与 B 细胞相关的疗效：因为 BTK 不仅存在于肥大细胞的免疫球蛋白 E（IgE）受体下游，还参与 B 细胞受体的下游通路。因此，一直有假说认为该药物会影响 CSU 患者的自身抗体水平，这也正是我们此次研究的核心方向。
我们的研究对象来自两项 Ⅲ 期临床试验（REMIX-1 和 REMIX-2 试验），这些患者临床特征明确，样本量较大。我们采集了患者在基线期、治疗第 24 周以及第 52 周治疗结束时的血液样本，检测其中的自身抗体水平；同时，我们还将具有 2 型自身免疫特征的患者（基础胰岛素释放检测呈阳性）与不具备该特征的患者分开分析。
研究结果显示：这些 2 型自身免疫性 CSU 患者在基线期的自身抗体水平确实处于升高状态，且在使用瑞米布替尼治疗期间会下降；而接受安慰剂治疗的患者，其自身抗体水平无任何变化。我们进一步研究 B 细胞特性后发现，非转换型 B 细胞的数量有所减少 —— 这类细胞被认为是产生免疫球蛋白 G（IgG）自身抗体的主要细胞，且不会分化为与正常 IgG 合成相关的常规长寿浆细胞。最后，我们检测了 B 细胞活化标志物可溶性 CD23（即免疫球蛋白 Fcε 受体 Ⅱ，FcεRⅡ）：在基线期，2 型患者的可溶性 CD23 水平更高（这提示存在自身免疫性疾病），而在接受瑞米布替尼治疗期间，该指标水平会下降。
目前这些数据尚属于描述性数据。接下来，我们需要将这些指标变化与临床结局进行关联分析，探究自身抗体水平降低与治疗疗效之间是否存在有意义的关联；同时，我们还需观察停药后的情况，判断自身抗体水平降低是否可能带来类似疾病修饰的效果，为患者带来长期益处 —— 让他们即使在停药后，也能保持无症状状态。非常感谢大家的聆听。
Hi, my name is Martin Metz. I'm professor of dermatology and allergology, and I'm deputy director at the institute of allergology at the Charite in Berlin Germany. I have the pleasure and privilege to report some new data here at the EADV, one of the possibly most exciting ones that was selected as an oral late breaking presentation, which is on the effects of Remibrutinib in chronic spontaneous urticaria (CSU).
Remibrutinib is a BTK inhibitor, that has been shown before, and we have published this, in CSU so it is a very effective drug that does work in our patients with CSU. What we have done now is to look more closely into effects that are not directly related to the mast cell, but rather to the B cell, because BTK is also downstream of the B cell receptor, not only the mast cell downstream of the IgE receptor, but also in the B cell receptor. So there has always been the hypothesis that this will affect the autoantibody levels in our patients with CSU, and this is exactly what we looked at.
We used the patient population from the phase 3 trials, from the REMIX-1 and REMIX-2 trial, so there's a large number of well characterized patients. We took blood at baseline, week 24, and at the end of treatment week 52, then looked for autoantibody levels—this was analyzed separately for patients with features of type 2 autoimmunity (those positive in the basal insulin release assay) versus those without type 2 features.
The result was that we indeed saw elevated autoantibody levels at baseline in these type 2 autoimmune CSU patients, and these levels were reduced during treatment with Remibrutinib, while there was no change in patients who received placebo. We further studied B cell characterization and found a decrease in non-switched B cells—these are considered the main producers of IgG autoantibodies and do not differentiate into regular long-lived plasma cells (which are relevant for normal IgG). Finally, we tested the B cell activation marker soluble CD23 (Fcε receptor II, FcεRⅡ): we observed higher soluble C
