Safety of synthetic and biological DMARDs: a systematic literature review informing the 2025 update of the EULAR recommendations for the management of rheumatoid arthritis.

Methods

Medline, Embase, Cochrane CENTRAL, and Web of Science were searched for observational and randomised controlled trials with a primary endpoint of DMARD safety on the conventional synthetic (cs-), biological (b-), and targeted synthetic-DMARDs, as well as glucocorticoids, published between January 14, 2022, and January 22, 2025.

在2022年1月14日至2025年1月22日期间发表的观察性和随机对照试验中，针对常规合成（cs-）、生物（b-）和靶向合成DMARDs以及糖皮质激素的DMARD安全性主要终点进行了检索，检索数据库包括Medline、Embase、Cochrane CENTRAL和Web of Science。

Separate searches on DMARD monitoring were conducted from database inception to January 22, 2025.

从数据库建立之初至2025年1月22日，对DMARD监测进行了单独的检索。

A comparator group was required for inclusion.

需要一个对照组才能纳入研究。

All safety outcomes were included.

所有安全性结果均被纳入。

Results

A total of 3837 articles were identified, with 321 selected for full-text review; 71 articles were included.

共识别出3837篇文章，其中321篇被选为全文审查；最终纳入了71篇文章。

Across the evidence base, infections were the most frequently assessed outcome: 13 studies examined serious or hospitalised infections, usually as composite endpoints of bacterial, opportunistic, and herpes zoster infection, while 1 addressed nonserious infections.

在现有证据中，感染是最频繁评估的结果：13项研究检查了严重或住院感染，通常是细菌、机会性和带状疱疹感染的综合终点，而1项研究关注了非严重感染。

Serious infections were more common with bDMARDs than csDMARDs.

与csDMARDs相比，bDMARDs的严重感染更为常见。

Janus kinase inhibitors (JAKis) showed a higher herpes zoster risk than bDMARDs.

Janus激酶抑制剂（JAKi）相较于生物制剂疾病修饰性抗风湿药物（bDMARDs），显示出更高的带状疱疹风险。

Tuberculosis risk was not increased with JAKis compared with bDMARDs, but was higher with infliximab and adalimumab compared with etanercept.

与bDMARDs相比，使用Janus激酶抑制剂（JAKi）并未增加结核病风险，但与依那西普相比，使用英夫利昔单抗和阿达木单抗时结核病风险更高。

Fifteen studies evaluated malignancy, split evenly between analyses of any malignancy and those excluding nonmelanoma skin cancer (NMSC); 2 focused on melanoma and 2 on NMSC.

十五项研究评估了恶性肿瘤，其中一半分析了任何类型的恶性肿瘤，另一半排除了非黑色素瘤皮肤癌（NMSC）；两项研究专注于黑色素瘤，两项专注于NMSC。

Increased NMSC was noted in patients with RA using DMARDs compared with the general population, with no link to a specific DMARD.

与普通人群相比，使用DMARDs的RA患者中观察到非黑色素瘤皮肤癌（NMSC）的增加，但与特定的DMARDs无关联。

Cardiovascular and thromboembolic events were reported in 20 studies.

20项研究中报告了心血管和血栓栓塞事件。

No consistent evidence of increased major adverse cardiovascular events risk with JAKis compared with bDMARDs was identified.

与bDMARDs相比，未发现JAKi增加主要不良心血管事件风险的一致证据。

Venous thromboembolism risk appeared elevated with JAKis compared with bDMARDs, driven mainly by pulmonary embolism.

与生物制剂疾病调节性抗风湿药物（bDMARDs）相比，JAK抑制剂（JAKis）的静脉血栓栓塞风险似乎有所提高，这主要由肺栓塞驱动。

Fourteen studies reported retention and adverse event-related withdrawals, and 8 assessed other specific adverse events.

有十四项研究报告了保留率和与不良事件相关的撤回情况，另外八项评估了其他特定的不良事件。

Gastrointestinal perforation and demyelinating disease were each reported in 3 studies.

胃肠道穿孔和脱髓鞘疾病在3项研究中各有报道。

No eligible articles were identified in searches on DMARD monitoring.

在关于DMARD监测的搜索中未发现符合条件的文章。

Conclusions

There has been a notable increase in studies evaluating safety outcomes, with the majority of these being observational studies focusing primarily on malignancy, thromboembolic, and cardiovascular events, with most studies pertaining to JAKi safety.

近年来，评估安全结果的研究显著增加，其中大多数为观察性研究，主要关注恶性肿瘤、血栓栓塞和心血管事件，大多数研究涉及JAKi的安全性。

A substantial proportion of studies in this SLR relied on claims databases to evaluate safety outcomes, a practice that carries important methodological limitations for safety research.

这项系统综述中相当一部分研究依赖于索赔数据库来评估安全结果，这种做法对安全研究的方法学限制至关重要。

Surprisingly, not many studies looked into glucocorticoid safety outcomes over the past 3 years.

令人惊讶的是，在过去3年中，很少有研究关注糖皮质激素的安全性结果。

This SLR, along with the SLR on efficacy of DMARDs, informed the 2025 update of the EULAR recommendations for management of RA with synthetic and biological DMARDs.

这项系统评价综述（SLR），连同关于疾病修饰性抗风湿药物（DMARDs）疗效的SLR，为2025年欧洲抗风湿病联盟（EULAR）关于使用合成和生物制剂DMARDs管理类风湿关节炎（RA）的推荐更新提供了信息。