Department of Rheumatology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
Int J Rheum Dis. 2024 Sep;27(9):e15311. doi: 10.1111/1756-185X.15311.
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation, joint swelling, and pain involving multiple joints. While biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are popular treatments for RA, there is limited research on their combined use. This study examined a cohort of RA patients who demonstrated inadequate response to bDMARDs and subsequently initiated combination therapy with tofacitinib and bDMARDs, assessing both the efficacy and safety profile of this therapeutic approach.
In this study, we retrospectively collected the electronic medical records (EMR) of 62 adult patients with RA who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between August 2018 and December 2022. All patients had received at least one bDMARD treatment for more than 3 months and still exhibited moderate-to-high disease activity. Tofacitinib 5 mg bid was added to their original biological treatment in 28 cases, and other 34 cases switched to another bDMARD or tsDMARD as control group. Treatment was continued for 24 weeks following the initiation of combination therapy. Changes in DAS28-ESR and ACR20, 50, 70 response rates at week 24 were collected and analyzed from baseline, while changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at weeks 4, 8, 12, 24 were also collected and analyzed.
After 24 weeks of treatment, the DAS28-ESR score in combined treatment group decreased significantly from a baseline of 5.26 ± 0.90 (3.87-8.31) to 2.67 ± 0.86 (1.41-5.11), with remission achieved by 19 patients (67.9%) and low disease activity achieved by five patients (17.9%). The DAS28-ESR in the control group exhibited a decrease from 5.20 ± 0.77 (3.87-7.23) at baseline to 3.25 ± 1.29 (1.54-5.69). In all, 13 patients (38.2%) achieved remission, while another 11 patients (32.4%) achieved low disease activity. The ACR20, 50, 70 response rates were 85.71%, 75%, and 39.29% in the combined treatment group, whereas it were 75.0%, 53.57%, 21.43% in the control group. Additionally, both ESR and CRP levels decreased significantly during the course of treatment without any reported adverse events leading to discontinuation.
Our findings offer some evidence, supporting the effectiveness and safety of combining bDMARD with JAKi tofacitinib in RA patients who have an inadequate response to bDMARD monotherapy. This combination effectively manages disease activity while maintaining a relatively low and manageable incidence of adverse events. Further prospective randomized controlled trials with large sample sizes are anticipated to provide evidence-based medical support.
类风湿关节炎（RA）是一种慢性系统性自身免疫性疾病，其特征为滑膜炎症、关节肿胀和疼痛，涉及多个关节。生物制剂疾病修饰抗风湿药物（bDMARDs）和靶向合成 DMARDs（tsDMARDs）是治疗 RA 的常用方法，但关于它们联合使用的研究有限。本研究观察了一组对 bDMARD 反应不足的 RA 患者，随后联合使用托法替尼和 bDMARD 进行治疗，评估了这种治疗方法的疗效和安全性。
本研究回顾性收集了 2018 年 8 月至 2022 年 12 月期间在浙江大学医学院附属第四医院就诊的 62 例成人 RA 患者的电子病历（EMR）。所有患者均接受了至少一种 bDMARD 治疗超过 3 个月，且仍存在中高度疾病活动。28 例患者在原有的生物治疗基础上加用托法替尼 5mg，bid；对照组 34 例患者转换为另一种 bDMARD 或 tsDMARD。在开始联合治疗后，继续治疗 24 周。从基线开始收集并分析第 24 周时 DAS28-ESR 和 ACR20、50、70 缓解率的变化，同时收集并分析第 4、8、12、24 周时 C 反应蛋白（CRP）和红细胞沉降率（ESR）的变化。
经过 24 周的治疗，联合治疗组的 DAS28-ESR 评分从基线时的 5.26±0.90（3.87-8.31）显著下降至 2.67±0.86（1.41-5.11），19 例患者（67.9%）达到缓解，5 例患者（17.9%）达到低疾病活动度。对照组的 DAS28-ESR 从基线时的 5.20±0.77（3.87-7.23）下降至 3.25±1.29（1.54-5.69）。共有 13 例患者（38.2%）达到缓解，11 例患者（32.4%）达到低疾病活动度。联合治疗组的 ACR20、50、70 缓解率分别为 85.71%、75%和 39.29%，对照组分别为 75.0%、53.57%和 21.43%。此外，两组在治疗过程中 ESR 和 CRP 水平均显著下降，且无不良事件导致停药。
本研究结果为 bDMARD 联合 JAKi 托法替尼治疗 bDMARD 单药治疗反应不足的 RA 患者的有效性和安全性提供了一定证据。这种联合治疗方法有效地控制了疾病活动度，同时保持了相对较低且可管理的不良反应发生率。预计将进行更大样本量的前瞻性随机对照试验，以提供基于证据的医学支持。
