背景:类风湿性关节炎(RA)是一种以滑膜炎为特征的慢性系统性自身免疫性疾病,关节肿胀,和多个关节的疼痛。虽然生物疾病改善抗风湿药(bDMARDs)和靶向合成DMARDs(tsDMARDs)是RA的流行治疗方法,对它们结合使用的研究有限。这项研究检查了一组RA患者,这些患者对bDMARDs的反应不足,随后开始了托法替尼和bDMARDs的联合治疗。评估这种治疗方法的有效性和安全性。
方法:在本研究中,我们回顾性收集了2018年8月至2022年12月浙江大学医学院附属第四医院收治的62例RA成年患者的电子病历(EMR).所有患者都接受了至少一次bDMARD治疗超过3个月,并且仍然表现出中度至高度的疾病活动性。在28例患者的原始生物治疗中添加了托法替尼5mgbid,其他34例改用另一个bDMARD或tsDMARD作为对照组。联合治疗开始后继续治疗24周。收集并分析第24周DAS28-ESR和ACR20、50、70反应率的变化,同时收集并分析第4、8、12、24周C反应蛋白(CRP)和红细胞沉降率(ESR)的变化。
结果:治疗24周后,联合治疗组DAS28-ESR评分从基线5.26±0.90(3.87-8.31)降至2.67±0.86(1.41-5.11),19例患者(67.9%)获得缓解,5例患者(17.9%)获得低疾病活动度。对照组的DAS28-ESR从基线时的5.20±0.77(3.87-7.23)降低至3.25±1.29(1.54-5.69)。总之,13例患者(38.2%)达到缓解,而另外11名患者(32.4%)的疾病活动度较低。ACR20、50、70有效率分别为85.71%,75%,联合治疗组为39.29%,而它是75.0%,53.57%,对照组为21.43%。此外,在治疗过程中,ESR和CRP水平均显著下降,未报告任何导致停药的不良事件.
结论:我们的发现提供了一些证据,支持bDMARD联合JAKi托法替尼治疗对bDMARD单药反应不足的RA患者的有效性和安全性.该组合有效地管理疾病活动,同时维持相对低的和可管理的不良事件发生率。进一步的大样本量的前瞻性随机对照试验预计将提供循证医学支持。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.