专家述评 | 李育林教授：长效护航健康，罗普司亭重塑ITP患者美好未来

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依据病程长短，ITP可分类为新诊断（0~3个月）、持续性（3~12个月）、慢性（>12个月），其中慢性形式发生在大约2/3的成人和20～25%的儿童中^[2]。ITP的治疗目标是维持患者血小板计数在安全水平，防止严重出血发生，推荐维持患者最低血小板>（20~30）×10⁹/L^[3]。

糖皮质激素仍然是ITP一线治疗的主要药物，然而，约20%～30%的患者对糖皮质激素治疗无应答，在有应答的患者中，约80%的患者在减少或停止使用激素时复发^[4]。虽然对激素有应答的患者可以通过持续使用激素治疗维持足够的血小板水平，但鉴于其不良反应如睡眠障碍、体重增加、高血糖和高血压等，不建议长期使用糖皮质激素，多数激素依赖的患者最终需要后续治疗^[4,5]。此外，另一种一线药物静脉注射免疫球蛋白（IVIg）价格较贵，每次使用后疗效维持时间通常仅3-4周。

TPO-RA的出现改变了ITP的治疗格局，多数一线治疗无效的ITP患者经TPO-RA治疗后血小板计数增加，持续应答率为60%～80%^[4]，《2019年ITP研究和诊治的国际共识报告》推荐其用于维持治疗，治疗的目标是达到血小板计数持续性上升，使药物不良反应最小化的同时维持机体止血平衡，以期获得疾病缓解^[3]。另外，部分患者在持续使用TPO-RA如罗普司亭治疗后停药，仍能维持安全的血小板计数，这可能与达到完全缓解后免疫耐受性恢复有关^[4]。

作为全球首个新型TPO-RA长效制剂，罗普司亭可与骨髓中许多造血细胞的TPO受体结合，包括巨核细胞和巨核前体细胞，激活多个信号通路（较小分子药物艾曲泊帕增加STAT3通路），促进细胞生长、巨核细胞核内有丝分裂和成熟^[6,7]，实现长期稳定的血小板数量提升。同时，罗普司亭与内源性TPO无序列同源性，这降低了免疫原性和后续自身抗体形成的理论风险^[8]，有助于实现稳定和可预测的血小板计数上升。另外，Treg在维持免疫耐受方面起着重要作用，ITP患者外周血中Treg的数量降低且功能受损^[9]，罗普司亭存在Fc片段，可与Fc受体相互作用，增强Treg活性，驱动免疫耐受，减少对血小板的破坏。一项研究比较了慢性ITP患者接受罗普司亭治疗前后的免疫学特征，发现罗普司亭可以提升转化生长因子β1（TGF-β1）水平、改善患者的Treg功能^[10]。

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