A randomized controlled pilot trial of anakinra for hemodialysis inflammation.
A randomized controlled pilot trial of anakinra for hemodialysis inflammation.
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DOI：
10.1016/j.kint.2022.06.022
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发表时间：
2022-11
影响因子：
19.6
通讯作者：
Ikizler, T. Alp
中科院分区：
文献类型：
--
作者：
Dember, Laura M.;Hung, Adriana;Mehrotra, Rajnish;Hsu, Jesse Y.;Raj, Dominic S.;Charytan, David M.;Mc Causland, Finnian R.;Regunathan-Shenk, Renu;Landis, J. Richard;Kimmel, Paul L.;Kliger, Alan S.;Himmelfarb, Jonathan;Ikizler, T. Alp
慢性炎症在接受维持性血液透析的患者中非常普遍，并且与发病率和死亡率相关。已经提出了用抗细胞因子疗法抑制炎症，但在该人群中没有得到很好的研究。因此，我们进行了ACTION试验，这是一项IL-1受体拮抗剂阿那白滞素的先导性、多中心、随机、安慰剂对照试验，旨在评估安全性、耐受性和可行性，并探索疗效。将80例血浆超敏C反应蛋白（hsCRP）浓度≥ 2 mg/L的血液透析患者按1：1随机分配至安慰剂组或阿那白滞素100 mg组，每周3次，通过血液透析回路，持续24周，并额外进行24周的治疗后安全性监测。疗效结局包括hsCRP（主要）、细胞因子和患者报告结局的变化。阿那白滞素和安慰剂组的严重不良事件和死亡率相似（严重不良事件：2.71 vs 2.74事件/患者年;死亡：0.12 vs 0.22事件/患者年）。阿那白滞素组的不良事件发生率（包括感染和血细胞减少）显著低于安慰剂组（0.48 vs 1.40事件/患者年）。通过达到入组目标、80%的留存率和72%的剂量给药证明了可行性。从基线到第24周，阿那白滞素组hsCRP的中位数下降为41%，安慰剂组为6%，组间差异无统计学意义。对于IL-6，中位降低是显著的;阿那白滞素组和安慰剂组分别为25%和0%。阿那白滞素对患者报告结局的影响不明显。因此，阿那白滞素耐受性良好，不会增加感染或血细胞减少症。有希望的安全性数据和对CRP和IL-6的潜在疗效为进行IL-1抑制剂的确定性试验以改善血液透析患者的结局提供了支持。
Chronic inflammation is highly prevalent among patients receiving maintenance hemodialysis and is associated with morbidity and mortality. Inhibiting inflammation with anti-cytokine therapy has been proposed but not well studied in this population. Therefore, we conducted the ACTION trial, a pilot, multicenter, randomized, placebo-controlled trial of an IL-1 receptor antagonist, anakinra, to evaluate safety, tolerability, and feasibility, and explore efficacy. Eighty hemodialysis patients with plasma concentrations of high sensitivity C-reactive protein (hsCRP) 2 mg/L and above were randomized 1:1 to placebo or anakinra 100 mg, three times per week via the hemodialysis circuit for 24 weeks, with an additional 24 weeks of post-treatment safety monitoring. Efficacy outcomes included change in hsCRP (primary), cytokines, and patient-reported outcomes. Rates of serious adverse events and deaths were similar with anakinra and placebo (serious adverse events: 2.71 vs 2.74 events/patient-year; deaths: 0.12 vs 0.22 events/patient-year). The rate of adverse events of interest (including infections and cytopenias) was significantly lower with anakinra than placebo (0.48 vs 1.40 events/patient-year). Feasibility was demonstrated by attaining the enrollment target, a retention rate of 80%, and administration of 72% of doses. The median decrease in hsCRP from baseline to Week 24 was 41% in the anakinra group and 6% in the placebo group, a between-group difference that was not statistically significant. For IL-6, the median decreases were significant; 25% and 0% in the anakinra and placebo groups, respectively. An effect of anakinra on patient-reported outcomes was not evident. Thus, anakinra was well tolerated and did not increase infections or cytopenias. The promising safety data and potential efficacy on CRP and IL-6 provide support for conducting definitive trials of IL-1 inhibition to improve outcomes in hemodialysis patients.
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影响因子：
2.3
作者：
Platz, Elizabeth A.;Sutcliffe, Siobhan;De Marzo, Angelo M.;Drake, Charles G.;Rifai, Nader;Hsing, Ann W.;Hoque, Ashraful;Neuhouser, Marian L.;Goodman, Phyllis J.;Kristal, Alan R.
通讯作者：
Kristal, Alan R.
影响因子：
19.6
作者：
PEREIRA, BJG;SHAPIRO, L;DINARELLO, CA
通讯作者：
DINARELLO, CA
影响因子：
13.3
作者：
Saag, Kenneth G.;Khanna, Puja P.;Terkeltaub, Robert
通讯作者：
Terkeltaub, Robert
影响因子：
13.6
作者：
Pergola, Pablo E.;Devalaraja, Matt;Davidson, Michael H.
通讯作者：
Davidson, Michael H.
影响因子：
13.2
作者：
Stenvinkel, P;Heimbürger, O;Jogestrand, T
通讯作者：
Jogestrand, T