利妥昔单抗治疗系统性硬化症患者的长期结局：DESIRES 试验的随访结果，重点关注血清免疫球蛋白水平。
Long-term Outcomes After Rituximab Treatment for Patients With Systemic Sclerosis: Follow-up of the DESIRES Trial With a Focus on Serum Immunoglobulin Levels.
机构信息
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
出版信息
JAMA Dermatol. 2023 Apr 1;159(4):374-383. doi: 10.1001/jamadermatol.2022.6340.
IMPORTANCE
Rituximab is emerging as a promising therapeutic option for systemic sclerosis (SSc), but its long-term outcomes and response markers are unknown.
OBJECTIVE
To evaluate the long-term outcomes after rituximab treatment for SSc and identify potential response markers.
DESIGN, SETTING, AND PARTICIPANTS: In this single-center cohort study, patients with SSc who continued to receive rituximab after the DESIRES trial were analyzed with a median follow-up of 96 weeks. Among the 43 patients who completed the DESIRES trial, 31 continued to receive rituximab, of which 29 with complete data were included in this study.
EXPOSURES
Rituximab treatment.
MAIN OUTCOMES AND MEASURES
A post hoc analysis of the clinical and laboratory data.
RESULTS
In 29 patients with SSc (27 female [93%]; median [IQR] age, 48 [35-45] years), significant improvement in modified Rodnan skin score (MRSS) and percentage of predicted forced vital capacity (FVC%) were observed after 1 (median [IQR] change in MRSS, -7 [-8.5 to -4]; P < .001) and 3 (median [IQR] change in FVC% predicted, 1.85 [0.13-5.68]; P < .001) courses of rituximab, respectively, both of which were sustained during follow-up. High responders (MRSS improvement of ≥9; n = 16) experienced a greater decrease in serum levels of IgG (median [IQR] change in IgG, -125 [-207 to -83] vs 7 [-120 to 43]; P = .008) and IgA (median [IQR] change in IgA, -45 [-96 to -32] vs -11 [-20 to 3]; P < .001) compared with low responders (MRSS improvement of ≤8; n = 13). In particular, decrease in serum IgA levels significantly correlated with the improvement in MRSS (r = 0.64; P < .001). At the last follow-up, low IgM, low IgA, and low IgG was observed in 7, 1, and 1 patient, respectively, of which low IgM was associated with greater improvement in FVC% predicted (median [IQR] change in FVC% predicted, 7.2 [3.8-8.9] vs 3.6 [1.4-6.2]; P = .003).
CONCLUSIONS AND RELEVANCE
In this cohort study, rituximab treatment was associated with significantly improved skin and lung fibrosis in SSc in a long-term follow-up. Decrease in serum immunoglobulins was associated with greater clinical response.
重要性：利妥昔单抗作为一种治疗系统性硬化症（SSc）的有前途的治疗选择正在出现，但它的长期结果和反应标志物尚不清楚。
目的：评估利妥昔单抗治疗 SSc 的长期结果，并确定潜在的反应标志物。
设计、地点和参与者：在这项单中心队列研究中，对 DESIRES 试验后继续接受利妥昔单抗治疗的 SSc 患者进行了分析，中位随访时间为 96 周。在完成 DESIRES 试验的 43 名患者中，有 31 名继续接受利妥昔单抗治疗，其中 29 名完成了完整数据的患者被纳入本研究。
暴露：利妥昔单抗治疗。
主要结果和测量：对临床和实验室数据进行了事后分析。
结果：在 29 名 SSc 患者（27 名女性[93%]；中位[IQR]年龄 48 [35-45]岁）中，在接受 1 次（中位数[IQR]改良 Rodnan 皮肤评分[MRSS]变化-7 [-8.5 至-4]；P<0.001）和 3 次（中位数[IQR]预计用力肺活量[FVC%]变化 1.85 [0.13-5.68]；P<0.001）利妥昔单抗治疗后，MRSS 和 FVC%预测值均显著改善，且在随访期间持续改善。高反应者（MRSS 改善≥9；n=16）的 IgG 血清水平下降更为明显（中位数[IQR] IgG 变化-125 [-207 至-83]与 7 [-120 至 43]；P=0.008）和 IgA（中位数[IQR] IgA 变化-45 [-96 至-32]与-11 [-20 至 3]；P<0.001），与低反应者（MRSS 改善≤8；n=13）相比。特别是，血清 IgA 水平的降低与 MRSS 的改善显著相关（r=0.64；P<0.001）。在最后一次随访时，分别有 7、1 和 1 名患者的 IgM、IgA 和 IgG 水平较低，其中 IgM 水平较低与 FVC%预测值的改善更大相关（中位数[IQR] FVC%预测值变化 7.2 [3.8-8.9]与 3.6 [1.4-6.2]；P=0.003）。
结论和相关性：在本队列研究中，利妥昔单抗治疗在 SSc 的长期随访中与皮肤和肺纤维化的显著改善相关。血清免疫球蛋白的降低与更大的临床反应相关。
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