Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase 2 trial.
Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase 2 trial.
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小剂量白介素 2 联合甲氨蝶呤治疗活动性类风湿关节炎患者的疗效和安全性：一项随机、双盲、安慰剂对照 2 期试验
DOI：
10.1038/s41392-022-00887-2
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发表时间：
2022-03-07
影响因子：
39.3
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Zhang X;Miao M;Zhang R;Liu X;Zhao X;Shao M;Liu T;Jin Y;Chen J;Liu H;Zhang X;Li Y;Zhou Y;Yang Y;Li R;Yao H;Liu Y;Li C;Li Y;Ren L;Su Y;Sun X;He J;Li Z
类风湿性关节炎(RA)是一种侵袭性自身免疫性关节炎，目前的治疗方法仍不能令人满意，原因是缓解率低和不良反应严重。小剂量白介素2(LD-IL2)是一种潜在的进一步改善疾病的治疗方法。这项随机、双盲、安慰剂对照试验被用来评估LD-IL2对活动期RA患者的疗效和安全性。患者被随机分配(1：1)接受LD-IL2，定义为100万国际单位的剂量，或在12周的试验中接受安慰剂，并进行12周的随访。每隔一天皮下注射三个周期的LD-IL2或安慰剂，共2周(共7剂)，然后休息2周。所有患者都接受了稳定剂量的甲氨蝶呤(MTX)治疗。主要结果是患者达到ACR20，DAS28-ESR&2.6的比例，以及在24周时CDAI或SDAI较基线的变化。次要终点包括其他临床反应和安全性。在按方案进行的人群中取得了初步成果。LD-IL2MTX组(n= + 17)与安慰剂+MTX组(n= 23)在不同时间点的CDAI和SDAI的改善明显大于安慰剂+MTX组(分别为P= 0.018和P= 0.015)。LD-IL2MTX组在12周(70.6%对43.5%)和24周(76.5%对56.5%) + 组的ACR20有效率高于安慰剂+MTX组(P= 0.014)。此外，低Treg和高IL-21与LD-IL2的良好反应相关。在本研究中，LD-IL-2治疗耐受性良好。提示LD-IL2治疗类风湿关节炎安全有效。临床试验.gov编号：nct 02467504。
Rheumatoid arthritis (RA) is an aggressive autoimmune arthritis, and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects. Low-dose interleukin-2 (Ld-IL2) is potentially a therapeutic approach to further improve the disease. This randomized, double-blind, placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA. Patients were randomly assigned (1:1) to receive Ld-IL2, defined as a dose of 1 million IU, or placebo in a 12-week trial with a 12-week follow-up. Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks (a total of 7 doses), followed by a 2-week break. All patients received a stable dose of methotrexate (MTX). The primary outcomes were the proportion of patients achieving the ACR20, DAS28-ESR <2.6, and the change from baseline in CDAI or SDAI at week 24. Secondary endpoints included other clinical responses and safety. The primary outcomes were achieved in the per-protocol population. The improvements from baseline in CDAI and SDAI were significantly greater across time points for the Ld-IL2 + MTX group (n= 17) than for the placebo+MTX group (n= 23) (P= 0.018 andP= 0.015, respectively). More patients achieved ACR20 response in the Ld-IL2 + MTX group than those in the placebo+MTX group at week 12 (70.6% vs 43.5%) and at week 24 (76.5% vs 56.5%) (P= 0.014). In addition, low Treg and high IL-21 were associated with good responses to Ld-IL2. Ld-IL-2 treatment was well-tolerated in this study. These results suggested that Ld-IL2 was effective and safe in RA. ClinicalTrials.gov number: NCT 02467504.
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DOI：
10.1084/jem.20061775
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sato K;Suematsu A;Okamoto K;Yamaguchi A;Morishita Y;Kadono Y;Tanaka S;Kodama T;Akira S;Iwakura Y;Cua DJ;Takayanagi H
通讯作者：
Takayanagi H
影响因子：
27.4
作者：
Rosenzwajg, Michelle;Lorenzon, Roberta;Klatzmann, David
通讯作者：
Klatzmann, David
影响因子：
4
作者：
Guggino, G.;Giardina, A.;Triolo, G.
通讯作者：
Triolo, G.
影响因子：
6
作者：
Kim, Kyoung-Woon;Kim, Hae-Rim;Lee, Sang-Heon
通讯作者：
Lee, Sang-Heon
影响因子：
1.6
作者：
Li R;Zhao JX;Su Y;He J;Chen LN;Gu F;Zhao C;Deng XR;Zhou W;Hao YJ;Xue Y;Liu HX;Zhao Y;Zou QH;Liu XY;Zhu P;Sun LY;Zhang ZL;Zou HJ;Li XF;Liu Y;Fang YF;Keystone E;McInnes IB;Li ZG
通讯作者：
Li ZG