Abstract

Objective

In the absence of a head-to-head study, we assessed the comparative effectiveness of pegcetacoplan, a targeted C3 complement inhibitor, vs. ravulizumab, a C5 complement inhibitor, among patients with paroxysmal nocturnal hemoglobinuria (PNH) previously treated with eculizumab using matching-adjusted indirect comparison methodology.

Methods

Individual patient data from the PEGASUS study (NCT03500549) comparing pegcetacoplan and eculizumab enabled adjustment for baseline differences compared with published results from the ALXN1210-PNH-302 study (NCT03056040), comparing ravulizumab and eculizumab. Adjusted differences and 95% confidence intervals (CIs) were computed via weighted Wald tests for comparisons of pegcetacoplan vs. ravulizumab, anchored to the common comparator eculizumab.

Results

Sixty-eight patients from PEGASUS (36 pegcetacoplan; 32 eculizumab) and 195 from ALXN1210-PNH-302 (97 ravulizumab; 98 eculizumab) were included. Compared with ravulizumab, treatment with pegcetacoplan was associated with more transfusion avoidance (adjusted difference [95% CI] = +71.4% [53.5%, 89.3%]), hemoglobin level stabilization (+75.5% [56.4%, 94.6%]), lactate dehydrogenase (LDH) level normalization (+64.0% [41.8%, 86.1%]), and fewer blood transfusions (−5.7 units [−7.2, −4.2]). Additionally, patients who received pegcetacoplan experienced clinically meaningful improvements in fatigue (+8.2 points [3.8, 12.6]), global health status (+9.6 points [0.1, 19.0]), physical functioning (+11.5 points [3.6, 19.5]), and fatigue symptoms (−13.3 points [−23.7, −3.0]), compared with ravulizumab. Mean change from baseline in LDH level was not significantly different for pegcetacoplan vs. ravulizumab.

Conclusions

Results suggest that among patients previously treated with eculizumab, clinical, hematological, and quality of life endpoints were better for patients who received the C3 complement inhibitor pegcetacoplan vs. patients who received ravulizumab, a C5 complement inhibitor.

中文翻译：

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pegcetacoplan 与 ravulizumab 在既往接受依库珠单抗治疗的阵发性睡眠性血红蛋白尿患者中的疗效比较：匹配调整的间接比较

摘要

客观的

在没有头对头研究的情况下，我们评估了靶向 C3 补体抑制剂 pegcetacoplan 与 C5 补体抑制剂 ravulizumab 在先前使用依库珠单抗治疗的阵发性睡眠性血红蛋白尿 (PNH) 患者中的比较有效性，使用匹配-调整后的间接比较方法。

方法

来自 PEGASUS 研究 (NCT03500549) 的个体患者数据比较了 pegcetacoplan 和依库珠单抗，与 ALXN1210-PNH-302 研究 (NCT03056040) 的已发表结果相比，可以调整基线差异，比较拉维珠单抗和依库珠单抗。通过加权 Wald 检验计算调整后的差异和 95% 置信区间 (CI)，以比较 pegcetacoplan 与 ravulizumab，锚定到常见的比较器 eculizumab。

结果

包括来自 PEGASUS 的 68 名患者（36 名 pegcetacoplan；32 名依库珠单抗）和 195 名来自 ALXN1210-PNH-302 的患者（97 名 ravulizumab；98 名依库珠单抗）。与 ravulizumab 相比，pegcetacoplan 治疗与更多避免输血相关（调整后差异 [95% CI] = +71.4% [53.5%, 89.3%]），血红蛋白水平稳定（+75.5% [56.4%, 94.6%]），乳酸脱氢酶 (LDH) 水平正常化（+64.0% [41.8%, 86.1%]）和更少的输血（-5.7 个单位 [-7.2, -4.2]）。此外，接受 pegcetacoplan 的患者在疲劳（+8.2 分 [3.8, 12.6]）、整体健康状况（+9.6 分 [0.1, 19.0]）、身体机能（+11.5 分 [3.6, 19.5]）、和疲劳症状（-13.3 分 [-23.7, -3.0]），与 ravulizumab 相比。

结论

结果表明，在先前接受过依库珠单抗治疗的患者中，接受 C3 补体抑制剂 pegcetacoplan 的患者与接受 C5 补体抑制剂 ravulizumab 的患者相比，临床、血液学和生活质量终点更好。