Transcutaneous auricular vagus nerve stimulation versus sham stimulation in patients with erosive hand osteoarthritis (ESTIVAL): a randomised, multicentre, double-blind, sham-controlled trial.

In this study we aimed to investigate the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) compared with sham stimulation in patients with inflammatory erosive hand osteoarthritis.

本研究旨在探讨经皮耳迷走神经刺激（taVNS）与假刺激相比，在治疗炎症性侵蚀性手部骨关节炎患者中的疗效。

Methods

ESTIVAL was a multicentre, randomised, double-blind, sham-controlled trial done in 18 French hospital centres (two secondary and 16 tertiary centres).

ESTIVAL 是一项在 18 家法国医院中心（包括两家二级中心和 16 家三级中心）进行的多中心、随机、双盲、安慰剂对照试验。

Adults (aged ≥18 years), fulfilling the American College of Rheumatology criteria for hand osteoarthritis with at least one erosive interphalangeal joint and ultrasound-confirmed synovitis were randomly assigned (1:1), stratified by site, using centralised web-based randomisation with computer-generated allocation, to receive either daily 20-min taVNS (VAGUSTIM, Schwa Medico, Rouffach, France) or sham stimulation (sham group; no electrical current) for 12 weeks.

符合条件的成年人（年龄 ≥18 岁），符合美国风湿病学会手骨关节炎的诊断标准，至少有一个侵蚀性指间关节，并且超声确认有关节炎，被随机分配（1:1），按中心分层，使用基于网络的中央随机化和计算机生成的分配，接受每天 20 分钟的 taVNS（VAGUSTIM，Schwa Medico，Rouffach，法国）或安慰剂刺激（安慰剂组；无电流）治疗 12 周。

The primary endpoint was change in hand pain on a visual analogue scale (VAS) from baseline to week 12.

主要终点是从基线到第12周手部疼痛在视觉模拟量表（VAS）上的变化。

Safety was assessed by recording adverse events and serious adverse events at each visit using a standardised form completed by investigators.

通过在每次访问时使用由研究者完成的标准表格记录不良事件和严重不良事件来评估安全性。

The primary outcome and safety were analysed in the intention-to-treatpopulation.

主要结果和安全性在意向治疗人群中进行了分析。

The trial was registered with ClinicalTrials.gov, NCT04520516, and is completed.

该试验已在ClinicalTrials.gov上注册，注册号为NCT04520516，并已完成。

No individuals with lived experience of hand osteoarthritis were involved in the design or conduct of the study.

没有参与手骨关节炎经验的个体参与了该研究的设计或实施。

Results

Between April 8, 2021, and March 29, 2022, 148 patients were enrolled in the study and 142 (96%) were randomly assigned (73 [51%] to the taVNS group and 69 [49%] to the sham group).

2021年4月8日至2022年3月29日期间，共有148名患者被纳入研究，其中142名（96%）被随机分配（73名[51%]至经皮迷走神经刺激组，69名[49%]至假刺激组）。

Overall, the mean age was 66·5 years (SD 8·4), 125 (88%) of 142 participants were female, and 17 (12%) were male.

总体来看，平均年龄为66.5岁（标准差8.4），142名参与者中有125名（88%）为女性，17名（12%）为男性。

At week 12, 63 (86%) of 73 participants in the taVNS group and 64 (93%) of 69 participants in the sham group provided primary outcome data.

在第12周时，73名接受经皮迷走神经刺激（taVNS）治疗的参与者中有63名（86%）提供了主要结果数据，而69名接受假治疗的参与者中有64名（93%）提供了主要结果数据。

Median change in VAS hand pain was -16·0 mm (IQR -32·0 to 5·0) in the taVNS group versus -6·0 mm (-27·0 to 7·0) in the sham group, giving an adjusted between-group difference of -10·0 mm (95% CI -23·0 to 2·0; p=0·22) at week 12; the primary endpoint was not met.

在经皮迷走神经刺激（taVNS）组中，手部疼痛的视觉模拟评分（VAS）中位数变化为-16.0毫米（四分位距-32.0至5.0毫米），而在假刺激组中为-6.0毫米（四分位距-27.0至7.0毫米），在第12周时两组之间的调整后差异为-10.0毫米（95%置信区间-23.0至2.0毫米；p=0.22），主要终点未达到。

No serious adverse events occurred.

没有发生严重不良事件。

Adverse events were reported by 22 (30%) of 73 participants in the taVNS and 16 (23%) and 69 participants in the sham group, with no emerging safety concerns.

在接受经皮迷走神经刺激（taVNS）的73名参与者中，有22人（30%）报告了不良事件，而在69名接受安慰剂治疗的参与者中，有16人（23%）报告了不良事件，未出现新的安全问题。

interpretation

In participants with erosive hand osteoarthritis, taVNS was safe and well tolerated.

在患有侵蚀性手部骨关节炎的参与者中，经皮迷走神经刺激（taVNS）是安全且耐受性良好的。

Although the primary endpoint was not met, the consistent pain reduction observed in patients with greater synovial inflammation suggests that taVNS merits further investigation in this erosive hand osteoarthritis population.

尽管主要终点未达成，但在滑膜炎症较重的患者中观察到的一致性疼痛减轻表明，经皮迷走神经刺激疗法（taVNS）值得在侵蚀性手骨关节炎人群中进一步研究。

funding

French Ministry of Health.

法国卫生部