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奥马珠单抗联合利妥昔单抗序贯治疗:重度特应性皮炎的新方法。

Sequential combined therapy with omalizumab and rituximab: a new approach to severe atopic dermatitis.

机构信息

Clinical Immunology Unit, Immunology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

出版信息

J Investig Allergol Clin Immunol. 2013;23(3):190-6.

Abstract

BACKGROUND

Atopic dermatitis (AD) is a common chronic skin disease, and a significant percentage of AD patients have severe forms. Inflammation based on type 2 helper T cells (T(H)2), autoantibodies, and CD8+ T cells could play a relevant role in this disease. When the patient requires systemic immunosuppressors for disease control, side effects are frequent. We propose a sequential therapeutic strategy with 2 monoclonal antibodies, omalizumab (anti-immunoglobulin [Ig] E) and rituximab (anti-CD20), which might induce clinical benefit with few side effects in selected individuals with AD.

METHODS

We report 6 cases of severe AD refractory to conventional therapy. The patients underwent sequential switch therapy with omalizumab and rituximab. Clinical response was assessed by means of the decrease in body surface affected. Immunological parameters and side effects were also monitored.

RESULTS

Four patients received omalizumab before a high-dose cycle of rituximab. In the case of recurrences, either low-dose cycles of rituximab or omalizumab were administered. A long-term clinical benefit was observed in 3 out of 4 patients. Two patients first received high-dose rituximab followed by either low-dose rituximab or omalizumab, and one of them achieved a response at 17 months. No severe side effects were recorded. Serum IgE level and B-cell counts decreased with therapy, the latter returning to baseline levels 10 to 11 months after treatment. Specific antibody responses remained protective during the study.

CONCLUSIONS

With our proposed switch therapy, 4 out of 6 patients achieved a dramatic clinical improvement. This novel strategy targets different arms of the immune response and might be a good alternative for patients with severe AD.

摘要

背景

特应性皮炎(AD)是一种常见的慢性皮肤病,有相当比例的 AD 患者为重度患者。基于 2 型辅助 T 细胞(T(H)2)、自身抗体和 CD8+T 细胞的炎症可能在这种疾病中发挥相关作用。当患者需要全身性免疫抑制剂来控制疾病时,副作用很常见。我们提出了一种序贯治疗策略,使用 2 种单克隆抗体,奥马珠单抗(抗免疫球蛋白[Ig]E)和利妥昔单抗(抗 CD20),这可能会在选择的 AD 患者中诱导出具有较少副作用的临床获益。

方法

我们报告了 6 例对常规治疗难治的重度 AD 患者。这些患者接受了奥马珠单抗和利妥昔单抗的序贯转换治疗。通过身体受影响面积的减少来评估临床反应。还监测了免疫参数和副作用。

结果

4 例患者在接受高剂量利妥昔单抗周期治疗前接受了奥马珠单抗。在复发的情况下,给予低剂量利妥昔单抗周期或奥马珠单抗。4 例中有 3 例观察到长期的临床获益。2 例患者首先接受了高剂量利妥昔单抗,然后接受了低剂量利妥昔单抗或奥马珠单抗,其中 1 例在 17 个月时出现了反应。没有记录到严重的副作用。治疗后血清 IgE 水平和 B 细胞计数下降,后者在治疗后 10 至 11 个月恢复到基线水平。在研究期间,特异性抗体反应保持保护性。

结论

通过我们提出的转换治疗,6 例患者中有 4 例获得了显著的临床改善。这种新策略针对免疫反应的不同方面,可能是重度 AD 患者的一个很好的选择。

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