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用于治疗中轴型脊柱关节炎的生物改善病情抗风湿药的个性化剂量减少策略:一项基于预测模型的临床和经济学评估

Personalized dose reduction strategies for biologic disease-modifying antirheumatic drugs for treating axial spondyloarthritis: a clinical and economic evaluation with predictive modeling.

作者信息

Binh Bui Hai, Phuong Nguyen Thi Thu, Hang Vu Thi Thanh, Nhan Ngo Thi Thuc, Hoa Nguyen Thi Nhu, Van Dung Hoang

机构信息

Centre of Rheumatology, Bach Mai Hospital, Hanoi, 100000, Vietnam.

Hai Phong University of Medicine and Pharmacy, Hai Phong, 180000, Vietnam.

出版信息

BMC Rheumatol. 2025 May 26;9(1):60. doi: 10.1186/s41927-025-00516-9.

Abstract

BACKGROUND

Axial spondyloarthritis (AS) is a chronic inflammatory disease that significantly affects quality of life and imposes a high economic burden on patients due to the cost of biologic disease-modifying antirheumatic drugs (bDMARDs). Dose reduction strategies for bDMARDs may offer a feasible approach to maintaining clinical efficacy while reducing costs. This study aimed to evaluate the clinical effectiveness and cost-efficiency of bDMARD dose reduction in patients with AS and apply machine learning to identify key factors influencing disease control.

METHODS

This 12-month prospective study, 368 AS patients receiving ≥ 3 months of full-dose bDMARDs were included. Among 215 initial responders (ASDAS < 2.1), 146 underwent dose reduction while 69 continued full-dose therapy. Clinical outcomes such as C-reactive protein (CRP) levels, the Bath ankylosing spondylitis disease activity index (BASDAI) and ankylosing spondylitis disease activity score (ASDAS) were assessed, along with cost effectiveness using incremental cost effectiveness ratios (ICER). Random forest models were developed to predict the achievement of inactive disease (ASDAS < 1.3) and to identify key predictors.

RESULTS

The dose reduction group demonstrated significantly greater improvements in CRP (-4.05 vs. +2.83 mg/L, p < 0.001), BASDAI (-3.00 vs. +0.89, p < 0.001), and ASDAS (-1.42 vs. +0.09, p < 0.001) compared to the full dose group. A greater proportion of patients in the reduced dose group achieved ASDAS < 1.3 at 12 months (93.2% vs. 33.3%, p < 0.001), with a shorter median time to response (4.20 vs. 4.70 months, p < 0.001). The ICER for achieving ASDAS < 1.3 was favorable (-$6,209.78; 95% CI:-$9,048.35 to-$4,015.78), supporting the cost-effectiveness of dose reduction. A random forest model identified reduced dose strategy, baseline ASDAS, BASDAI, treatment duration, and CRP as key predictors of ASDAS < 1.3, achieving an AUC of 0.845 and F1-score of 0.774.

CONCLUSIONS

In this cohort, bDMARD dose reduction was associated with preserved clinical outcomes and lower costs, suggesting it may be a viable strategy for selected patients under close clinical supervision. Predictive modeling provided actionable insights to optimize personalized treatment strategies, balancing efficacy and economic sustainability. These findings support further evaluation of dose reduction strategies, especially in resource-limited settings, to inform potential integration into routine practice.

摘要

背景

轴性脊柱关节炎(AS)是一种慢性炎症性疾病,严重影响生活质量,由于生物性改善病情抗风湿药物(bDMARDs)的费用,给患者带来高昂的经济负担。bDMARDs的剂量减少策略可能提供一种可行的方法,既能维持临床疗效又能降低成本。本研究旨在评估bDMARD剂量减少在AS患者中的临床有效性和成本效益,并应用机器学习来识别影响疾病控制的关键因素。

方法

这项为期12个月的前瞻性研究纳入了368例接受≥3个月全剂量bDMARDs治疗的AS患者。在215例初始缓解者(ASDAS<2.1)中,146例进行了剂量减少,69例继续全剂量治疗。评估了临床结局,如C反应蛋白(CRP)水平、巴斯强直性脊柱炎疾病活动指数(BASDAI)和强直性脊柱炎疾病活动评分(ASDAS),并使用增量成本效益比(ICER)评估成本效益。开发了随机森林模型来预测疾病非活动状态(ASDAS<1.3)的实现,并识别关键预测因素。

结果

与全剂量组相比,剂量减少组在CRP(-4.05 vs. +2.83mg/L,p<0.001)、BASDAI(-3.00 vs. +0.89,p<0.001)和ASDAS(-1.42 vs. +0.09,p<0.001)方面有显著更大的改善。剂量减少组中更大比例的患者在12个月时达到ASDAS<1.3(93.2% vs. 33.3%,p<0.001),中位反应时间更短(4.20 vs. 4.70个月,p<0.001)。实现ASDAS<1.3的ICER是有利的(-$6,209.78;95%CI:-$9,048.***35至-$4,015.78),支持剂量减少的成本效益。随机森林模型将剂量减少策略、基线ASDAS、BASDAI、治疗持续时间和CRP识别为ASDAS<1.3的关键预测因素,AUC为0.845,F1分数为0.774。

结论

在该队列中,bDMARD剂量减少与保留临床结局和降低成本相关,表明在密切临床监督下,这可能是选定患者的可行策略。预测模型提供了可操作的见解,以优化个性化治疗策略,平衡疗效和经济可持续性。这些发现支持进一步评估剂量减少策略,特别是在资源有限的环境中,以便为潜在纳入常规实践提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e1b/12105312/1ed7ce78fcf3/41927_2025_516_Fig1_HTML.jpg

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