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托法替尼治疗青少年特发性关节炎疗效显著
作者:小柯机器人 发布时间:2021/11/13 22:25:24

意大利IRCCS Gaslini儿童医院研究了托法替尼治疗青少年特发性关节炎的疗效。相关论文于2021年11月9日发表在《柳叶刀》杂志上。

托法替尼是一种口服Janus激酶抑制剂。该研究评估了托法替尼与安慰剂在多关节青少年特发性关节炎(JIA)患者中的有效性和安全性。

研究组在儿科风湿病国际试验组织的64个中心和14个国家的儿科风湿病合作研究小组网络中进行了一项双盲、停药3期试验,招募年龄在2-18岁的多关节病程JIA患者(扩展性少关节炎、类风湿因子阳性或类风湿因子阴性多关节炎,或无全身活动性特征的系统性JIA)。银屑病关节炎或附着点炎相关关节炎患者被纳入探索性终点。

在研究的第1部分中,患者接受口服开放标签托法替尼治疗18周。至少达到JIA/美国风湿病学会30缓解的患者被随机分配(1:1),在研究第2部分继续服用托法替尼或改用安慰剂治疗26周。主要终点为第2部分多关节病程JIA患者第44周的JIA发作率,采用了意向治疗原则。对整个研究的患者进行安全性评估。

2016年6月10日至2019年5月16日,研究组共招募了225名患者,其中184名(82%)患有多关节疾病,20名(9%)患有银屑病性关节炎,21名(9%)患有附着点炎相关关节炎。225例患者中147例(65%)同时服用甲氨蝶呤。在第2部分中,142名多关节病程的患者被分为托法替尼组(n=72)或安慰剂组(n=70)。

第44周时,托法替尼组中有21名(29%)发作,显著低于安慰剂组(37名[53%]),危险比为0.46。在该研究的第2部分中,88名接受托法替尼治疗的患者中有68名(77%)发生不良事件,而安慰剂组85名患者中有63名(74%)。严重不良事件发生率分别为1%和2%。在整个托法替尼暴露期间,225名患者中有107名(48%)感染或被侵袭。本研究期间没有死亡病例。

这项关键性试验的结果表明,托法替尼是治疗多关节病变的有效方法。新的口服疗法特别适合儿童和青少年,他们可能更愿意避免注射。

附:英文原文

Title: Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial

Author: Nicolino Ruperto, Hermine I Brunner, Olga Synoverska, Tracy V Ting, Carlos Abud Mendoza, Alberto Spindler, Yulia Vyzhga, Katherine Marzan, Lyudmila Grebenkina, Irit Tirosh, Lisa Imundo, Rita Jerath, Daniel J Kingsbury, Betul Sozeri, Sheetal S Vora, Sampath Prahalad, Elena Zholobova, Yonatan Butbul Aviel, Vyacheslav Chasnyk, Melissa Lerman, Kabita Nanda, Heinrike Schmeling, Heather Tory, Yosef Uziel, Diego O Viola, Holly B Posner, Keith S Kanik, Ann Wouters, Cheng Chang, Richard Zhang, Irina Lazariciu, Ming-Ann Hsu, Ricardo M Suehiro, Alberto Martini, Daniel J Lovell, R Cuttica, J Akikusa, J Chaitow, C Wouters, S Oliveira, CLS Neiva, M Santiago, CA Silva, MT Terreri, C Magalhaes, V De Souza, M Bandeira, G Chédeville, K Houghton, M Vazquez-Del Mercado, J Rizo Rodriguez, K Kobusinska, E Alexeeva, I Calvo Penades, AL Boteanu, O Kasapcopur, MH Poyrazoglu, M Erguven, S Ozen, E Al-Abadi, J Bohnsack, R Carrasco, J Dare, B Gottlieb, D Wahezi, L Jung, M Klein-Gitelman, Y Zhang, L Wagner-Weiner, S Tarvin, RK Vehe, P Chiraseveenuprapund, R Rivas-Chacon, W De La Pena, ACP Sagcal-Gironella, JE Weiss

Issue&Volume: 2021-11-09

Abstract:

Background

Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA).

Methods

This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434.

Findings

Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 [29%] of 72 patients) than with placebo (37 [53%] of 70 patients; hazard ratio 0·46, 95% CI 0·27–0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study.

Interpretation

The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections.

DOI: 10.1016/S0140-6736(21)01255-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01255-1/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet