Recombinant herpes zoster vaccine in patients with autoimmune rheumatic diseases in Brazil: a double-blind, randomised, placebo-controlled, phase 4, non-inferiority study.

We evaluated the effect of a recombinant zoster vaccine in patients with autoimmune rheumatic diseases compared with placebo and in healthy controls.

我们评估了重组带状疱疹疫苗在自身免疫性风湿病患者中的效果，与安慰剂和健康对照组进行了比较。

Methods

This single-centre, double-blind, randomised, placebo-controlled, phase 4, non-inferiority, study was done at a tertiary centre in Brazil.

这项单中心、双盲、随机、安慰剂对照、第四阶段、非劣效性研究在巴西的一家三级中心进行。

Eligible patients were aged 18 years or older with an autoimmune rheumatic disease diagnosis.

符合条件的患者年龄为18岁或以上，并被诊断为自身免疫性风湿病。

All patients had to have been managed with glucocorticoids, immunosuppressives, or disease-modifying antirheumatic drugs, provided the doses were stable for at least 4-12 weeks before the initial study visit.

所有患者必须在初始研究访问前至少4-12周内使用糖皮质激素、免疫抑制剂或疾病修饰性抗风湿药物进行管理，并且剂量保持稳定。

Patients were randomly assigned (1:1) to receive two doses of recombinant zoster vaccine or placebo, 6 weeks apart, according to computer-generated sequences, without blocks or stratification.

患者按1:1的比例随机分配，接受两剂重组带状疱疹疫苗或安慰剂，间隔6周，根据计算机生成的序列进行，不使用区块或分层。

Investigators and participants were masked to treatment allocation.

研究人员和参与者对治疗分配情况进行了盲法处理。

Healthy controls were also included from the same centre and received two doses of the recombinant zoster vaccine.

同时，从同一中心纳入了健康对照组，并接受了重组带状疱疹疫苗的两剂接种。

Following the double-blindphase, patients with autoimmune rheumatic diseases who initially received placebo entered an open-label phase and received two doses of the vaccine.

在双盲阶段之后，最初接受安慰剂的自身免疫性风湿病患者进入开放标签阶段，并接受了两剂重组带状疱疹疫苗。

The primary outcome was the number of patients with autoimmune rheumatic diseases with worsening of disease activity (flare) up to day 84 after the first dose of the recombinant zoster vaccine compared with placebo in the double-blindphase of the study.

主要结果是与双盲阶段安慰剂组相比，首次接种重组带状疱疹疫苗后84天内自身免疫性风湿病患者病情加重（发作）的患者数量。

Non-inferiority of recombinant zoster vaccine would be declared if the upper boundary of the one-sided 95% CI for the rate of worsening in disease activity in the group receiving recombinant zoster vaccine versus the placebo group was less than 5%.

如果重组带状疱疹疫苗组疾病活动恶化率的单侧95%置信区间上限小于5%，则宣布其非劣效性。

The primary analysis (flare rates) and the safety analysis were done in all participants who received at least one vaccine dose.

主要分析（发作率）和安全性分析是在所有至少接种了一剂疫苗的参与者中进行的。

There was no involvement of people with lived experience of autoimmune rheumatic diseases in the study design.

在研究设计中没有涉及自身免疫性风湿病患者的生活经历。

The study is registered with ClinicalTrials.gov (NCT05879419) and is complete.

该研究已在ClinicalTrials.gov注册（NCT05879419），研究已经完成。

Results

Between May 25, 2023, and Nov 27, 2024, 1192 patients were enrolled in the study and were randomly assigned to receive either the recombinant zoster vaccine (n=590) or placebo (n=602). 559 (95%) of 590 patients in the recombinant vaccine group and 577 (96%) of 602 in the placebo group received at least one dose of the recombinant zoster vaccine or placebo and were included in the primary outcome and safety analyses; 891 (78%) of 1136 were female, 245 (22%) were male, 555 (49%) were of African descent, and 552 (49%) were White.

在2023年5月25日至2024年11月27日期间，共有1192名患者参与了本研究，并被随机分配接受重组带状疱疹疫苗(n=590)或安慰剂(n=602)。重组疫苗组中有559名（95%）患者和安慰剂组中有577名（96%）患者至少接受了重组带状疱疹疫苗或安慰剂的一剂，并被纳入主要结果和安全性分析；在1136名患者中，891名（78%）为女性，245名（22%）为男性，555名（49%）为非洲裔，552名（49%）为白人。

An additional 393 healthy controls were enrolled in the study: 380 received both doses of the recombinant zoster vaccine and were included in the safety analyses.

另外，研究中还招募了393名健康对照者：其中380人接受了重组带状疱疹疫苗的两剂，并被纳入安全性分析。

For the primary outcome of worsening of disease activity (flare) up to day 84 for patients with autoimmune rheumatic diseases, non-inferiority was shown for the recombinant zoster vaccine group compared with placebo. 80 (14%) of 559 patients in the recombinant zoster vaccine group had a flare compared with 84 (15%) of 557 in the placebo group, equating to a between-group difference in flare rate of -1·2% (95% CI -4·7 to 2·2; pnon-inferiority=0·0018).

对于自身免疫性风湿病患者的疾病活动恶化（发作）的主要结果，重组带状疱疹疫苗组与安慰剂相比显示出非劣效性。重组带状疱疹疫苗组的559名患者中有80名（14%）出现发作，而安慰剂组的557名患者中有84名（15%）出现发作，两组之间的发作率差异为-1.2%（95%置信区间-4.7至2.2；p非劣效性=0.0018）。

Adverse events were less frequently reported after both vaccine doses in patients with autoimmune rheumatic diseases compared with the healthy control group (after first dose: 430 [77%] of 559 in the recombinant zoster vaccine group vs 179 [31%] of 577 in the placebo group vs 341 [90%] of 380 in the healthy control group; after the second dose: 402 [72%] vs 148 [26%] vs 307 [81%]).

在自身免疫性风湿病患者中，两剂疫苗接种后报告的不良事件比健康对照组少（第一剂后：重组带状疱疹疫苗组的559名患者中有430名（77%），安慰剂组的577名患者中有179名（31%），健康对照组的380名患者中有341名（90%）；第二剂后：402名（72%）vs 148名（26%）vs 307名（81%））。

Serious adverse events were similar across the groups after the first dose (five [1%] vs six [1%] vs none) and second dose (nine [2%] vs five [1%] vs two [1%]) of the recombinant zoster vaccine.

重组带状疱疹疫苗首次和第二次接种后，各组严重不良事件相似（分别为五例[1%]对六例[1%]对无），（九例[2%]对五例[1%]对两例[1%]）

interpretation

Recombinant zoster vaccine had an acceptable safety profile in patients with autoimmune rheumatic diseases who are immunosuppressed, and had no significant effect on short-term disease activity.

重组带状疱疹疫苗在自身免疫性风湿病患者中具有可接受的安全性，这些患者处于免疫抑制状态，并且对短期疾病活动没有显著影响。

funding

GSK and the Fundação de Amparo à Pesquisa do Estado de São Paulo.

葛兰素史克公司与圣保罗州研究支持基金会