Immunogenicity of Adalimumab in Patients with Non-Infectious Uveitis: Systematic Review and Meta-Analysis

To review the prevalence, incidence, and risk factors for developing anti-drug antibodies (AAA) in patients with non-infectious uveitis (NIU) treated with Adalimumab (ADA). A systematic literature search was performed on PubMed, EMBASE, Virtual Health Library, Cochrane, and medRxiv. Meta-analysis was performed using random effects. Nine out of 2,373 studies were included. The prevalence of AAA in NIU patients treated with ADA was 9% (95% CI: 2% to 37%, I² = 95% with a P<0.01), it was significantly higher in real-life scenarios (observational studies) than in clinical trials. The pooled incidence at 12 months was 27% (CI 95% 16%-42% I² = 0%). Several factors have been associated with AAA generation in NIU patients, including the non-use of concomitant immunosuppressants, presence of autoimmune systemic disease, female gender, etc. This study showed that AAA prevalence is higher in real-life scenarios compared to clinical trials. Further research is needed to elucidate the factors that trigger AAA generation in NIU patients.

本研究旨在评估接受阿达木单抗（Adalimumab, ADA）治疗的非感染性葡萄膜炎（non-infectious uveitis, NIU）患者体内抗药物抗体（anti-drug antibodies, AAA）的患病率、发生率及相关危险因素。研究团队对PubMed、EMBASE、虚拟健康图书馆（Virtual Health Library）、考克兰数据库（Cochrane）及medRxiv平台开展系统文献检索，并采用随机效应模型进行荟萃分析。最终纳入2373项研究中的9项。接受ADA治疗的NIU患者中，AAA的患病率为9%（95%置信区间：2%~37%，I²=95%，P<0.01）；真实世界场景（观察性研究）中的患病率显著高于临床试验。12个月时的合并发生率为27%（95%置信区间：16%~42%，I²=0%）。多项因素与NIU患者的AAA生成相关，包括未使用伴随免疫抑制剂、合并全身性自身免疫性疾病、女性性别等。本研究证实，真实世界场景中AAA的患病率高于临床试验；未来仍需开展进一步研究以阐明NIU患者AAA生成的触发因素。