Patients with rheumatic and musculoskeletal diseases (RMDs) who are taking immunosuppressants have been considered to be at increased risk of developing SARS–CoV-2 infection during the COVID-19 pandemic, and vaccination is the mainstay for the prevention of this infection (1). To date, recommendations and data for COVID-19 vaccination in adolescent patients with RMDs are lacking (2). Reports from international societies and post-authorization safety studies of the novel messenger RNA (mRNA) COVID-19 vaccines are generally reassuring; however, in adolescent RMD patients treated with immunomodulators, the safely profile of mRNA COVID-19 vaccines is unknown because adolescents with RMD were excluded from the vaccine trials (3-5). Furthermore, there is a theoretical risk of RMD flare related to the mRNA COVID-19 vaccines (1, 2). Nevertheless, the estimated risks and benefits clearly favor vaccination (1, 2). In a population of adult RMD patients receiving non–B cell–depleting therapy, it was demonstrated that after 2 doses of a COVID-19 mRNA vaccine, the vast majority of patients developed a positive antibody response (though data on relative amount of antibody responses are still lacking) and experienced only minor side effects with no apparent disease exacerbation/flare (6).

Recently we performed a study that aimed to evaluate the safety and tolerability of the BNT162b2 COVID-19 vaccine (BioNTech; Pfizer) in adolescents with juvenile idiopathic arthritis (JIA) treated with tumor necrosis factor (TNF) inhibitors. This single-center study included adolescent patients (ages 16–21 years) with stable JIA who had been receiving treatment with TNF inhibitors for at least 1 year following the diagnosis. Written informed consent was obtained at enrollment. The patients received 2 doses of the COVID-19 mRNA vaccine intramuscularly, with the initial dose and follow-up dose administered between April 15 and May 15, 2021 (designated 0 weeks and 3 weeks, respectively). Follow-up visits were planned for 1, 2, and 3 months after vaccination. All participants were observed for 30 minutes after the injection and were given a diary card to record the occurrence of local or systemic symptoms for the following 14 days. Adverse reactions were defined as any reaction that lasted for >7 days after vaccination, and serious adverse reactions were defined as any reaction requiring medical attention or hospitalization. Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score in 27 joints (JADAS-27) (7). Data were analyzed using SPSS version 18.0 software. P values less than 0.05 were considered significant.

A total of 21 adolescent patients were enrolled in our study. Demographic and clinical characteristics are shown in Table 1. Both doses of the vaccine were well tolerated by all of the participants. Local reactions were frequent in the majority of participants (74%) (Table 1). No difference in reaction was noted between the patients taking etanercept versus those taking adalimumab (71% versus 75%, respectively; P = 0.09) or in patients with different JIA types. In addition, systemic reactions were relatively infrequent (19%) (Table 1). There were no differences in the rates of systemic reactions according to the type of JIA or the medication received. Most localized and systemic reactions were noted after the second dose of the vaccine (P = 0.02). One patient developed hives after the second dose, which was alleviated with antihistamines. JIA was in clinical remission in all patients at the time of vaccination. No exacerbation of underlying disease was noted, based on evaluation of the JADAS-27 at 1 month before the vaccination, as well as at 1 and 3 months after the second dose of vaccination (Figure 1). There were no significant changes in the JADAS-27 (P = 0.417) or in laboratory test results (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count) at follow-up over a period of 3 months (P = 0.1, P = 0.09, and P = 0.4, respectively) (data not shown). None of the participants discontinued treatment with TNF inhibitors at the time of vaccine administration or during the follow-up period.

This is the first study demonstrating that mRNA vaccines appear to be safe and well tolerated in adolescents with JIA receiving treatment with TNF inhibitors. Although our sample size was small and a limited number of patients were included within each JIA type and treatment group, it may be concluded that the vaccine has an adequate safety and tolerability profile and does not provoke disease flare. As there are no studies examining the safety and effectiveness of COVID-19 vaccines in this population, further studies are needed to evaluate the immune response, analyze the immunogenicity of the 2-dose schedule, and determine the real duration of immune protection.

在 COVID-19 大流行期间，服用免疫抑制剂的风湿性和肌肉骨骼疾病 (RMD) 患者被认为发生 SARS-CoV-2 感染的风险增加，而疫苗接种是预防这种感染的主要手段 ( 1 ) . 迄今为止，缺乏对患有 RMD 的青少年患者进行 COVID-19 疫苗接种的建议和数据 ( 2 )。来自国际社会的报告和新型信使 RNA (mRNA) COVID-19 疫苗的授权后安全性研究通常令人放心；然而，在接受免疫调节剂治疗的青少年 RMD 患者中，mRNA COVID-19 疫苗的安全性尚不清楚，因为患有 RMD 的青少年被排除在疫苗试验之外（3-5）。此外，理论上存在与 mRNA COVID-19 疫苗相关的 RMD 爆发风险 ( 1, 2 )。然而，估计的风险和收益显然有利于接种疫苗 ( 1, 2 )。在接受非 B 细胞耗竭疗法的成年 RMD 患者群体中，证明在接种 2 剂 COVID-19 mRNA 疫苗后，绝大多数患者产生了阳性抗体反应（尽管有关抗体反应相对数量的数据仍然缺乏）并且仅经历了轻微的副作用，没有明显的疾病恶化/发作（6）。

最近，我们进行了一项研究，旨在评估 BNT162b2 COVID-19 疫苗 (BioNTech; Pfizer) 在青少年特发性关节炎 (JIA) 患者中使用肿瘤坏死因子 (TNF) 抑制剂治疗的安全性和耐受性。这项单中心研究包括患有稳定型 JIA 的青少年患者（年龄 16-21 岁），这些患者在诊断后已接受 TNF 抑制剂治疗至少 1 年。入组时获得书面知情同意书。患者肌肉内接受了 2 剂 COVID-19 mRNA 疫苗，初始剂量和后续剂量在 2021 年 4 月 15 日至 5 月 15 日之间给药（分别指定为 0 周和 3 周）。计划在接种疫苗后 1、2 和 3 个月进行随访。注射后观察所有参与者 30 分钟，并给予日记卡以记录随后 14 天局部或全身症状的发生情况。不良反应定义为接种疫苗后持续>7天的任何反应，严重不良反应定义为任何需要就医或住院治疗的反应。使用 27 个关节的青少年关节炎疾病活动评分 (JADAS-27) 评估疾病活动性（7）。使用SPSS 18.0版软件对数据进行分析。P值小于0.05被认为是显着的。

我们的研究共招募了 21 名青少年患者。人口统计学和临床​​特征见表 1。所有参与者都很好地耐受了两种剂量的疫苗。大多数参与者 (74%) 经常出现局部反应（表 1）。服用依那西普的患者与服用阿达木单抗的患者（分别为 71% 和 75%；P  = 0.09）或不同 JIA 类型的患者之间的反应没有差异。此外，全身反应相对较少（19%）（表 1）。根据 JIA 的类型或接受的药物，全身反应的发生率没有差异。在第二剂疫苗接种后发现大多数局部和全身反应（P = 0.02)。一名患者在第二次给药后出现荨麻疹，抗组胺药缓解了这种情况。在接种疫苗时，所有患者的 JIA 均处于临床缓解期。根据在疫苗接种前 1 个月以及第二剂疫苗接种后 1 个月和 3 个月对 JADAS-27 的评估，未发现潜在疾病恶化（图 1）。JADAS-27 ( P  = 0.417) 或实验室检测结果（C 反应蛋白、红细胞沉降率和白细胞计数）在 3 个月的随访中没有显着变化（P  = 0.1 , P  = 0.09, 和P = 0.4，分别）（数据未显示）。没有参与者在疫苗接种时或随访期间停止使用 TNF 抑制剂治疗。

这是第一项研究表明 mRNA 疫苗在接受 TNF 抑制剂治疗的 JIA 青少年中似乎是安全且耐受性良好的。尽管我们的样本量很小，并且每个 JIA 类型和治疗组中包含的患者数量有限，但可以得出结论，该疫苗具有足够的安全性和耐受性，并且不会引起疾病发作。由于没有研究检查 COVID-19 疫苗在该人群中的安全性和有效性，因此需要进一步的研究来评估免疫反应，分析 2 剂方案的免疫原性，并确定免疫保护的实际持续时间。