第24周SDAI缓解能否预测远期RA骨破坏受抑制

第24周SDAI缓解能否预测远期RA骨破坏受抑制

Hirano F, et al. EULAR 2015. Present ID:THU0085.

 

原文

译文

THU0085

SDAI REMISSION AT WEEK 24 IS A PREDICTOR OF GOOD FUNCTIONAL AND STRUCTURAL OUTCOMES AT WEEK 72 IN A T2T IMPLEMENTING COHORT

F. Hirano^1,2,*, W. Yokoyama^1,2, H. Yamazaki^1,2, K. Amano³, Y. Kaneko⁴, A. Kawakami⁵, T. Matsui⁶, R. Sakai¹, R. Koike^1,2, N. Miyasaka², M. Harigai^1,2

¹Department of Pharmacovigilance, ²Department of Rheumatology, Tokyo Medical and Dental University, Tokyo, ³Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Kawagoe, ⁴Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, ⁵Unit of Translational Medicine, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, ⁶Department of Rheumatology, Sagamihara National Hospital, National Hospital Organization, Sagamihara, Japan

   

Background: In the treat-to-target strategy (T2T)¹, simplified disease activity index (SDAI) has been proposed as one of measures to define remission². Predictive ability of SDAI remission for functional and structural outcomes was shown by data from clinical trials, but has not been proven in a T2T implementing cohort.

Objectives: To examine if achieving SDAI remission is a predictor of good functional and structural outcomes in a T2T implementing cohort.

Methods: The T2T Epidemiological Study is a multi-centre, prospective cohort study, in which RA patients with moderate to high disease activity were enrolled and treated with T2T for 72 weeks. The disease activity was assessed every 12 weeks and the treatment was adjusted accordingly. Primary outcomes were HAQ and ∆mTSS at week 72. Multivariate logistic regression analysis was used to examine association between SDAI remission at week 24 and the two primary outcomes. Missing data were imputed using the multiple imputation method. Statistical significance levels were adjusted for multiple comparison using False Discovery Rate and BH methods.

Results: Of total 318 enrolled patients, 244 patients followed up for 72 weeks were analysed. Patient characteristics were as follows: female, 77%; mean age, 61; mean disease duration, 57 months. At week 24, 33% achieved SDAI remission. At week 72, 50% achieved SDAI remission, 61% achieved HAQ remission (≤0.5) and 73% showed ΔmTSSp=0.009], baseline HAQ [0.30 (0.19-0.47), p=2.4x10^-7], absence of history of joint replacement related to RA [9.90 (1.57-62.5), p=0.015] and SDAI remission at week 24 [3.24 (1.57-6.71), p=0.0015]. Factors associated with ΔmTSSp=0.0037], serum MMP-3 level at week 24 [0.998(0.996-1.000), p=0.035] and SDAI remission at week 24 [3.21 (1.46-7.02), p=0.0036].

Conclusions: SDAI remission at week 24 is a significant predictor of good functional and structural outcomes at week 72 in the T2T implementing cohort.

References: 1. Ann Rheum Dis 2010;68:631-637. 2. Ann Rheum Dis. 2011;70:404-413.

Acknowledgements: We all thank all health care professionals and patients who participated in this study.

Disclosure of Interest: F. Hirano: None declared, W. Yokoyama: None declared, H. Yamazaki Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis KK., Santen Pharmaceutical Co., Ltd., Sekisui Medical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., and UCB Japan, K. Amano Grant/research support from: Astellas, Chugai, Pfizer, Tanabe-Mitsubishi, Consultant for: Zenyaku Kogyo, Paid instructor for: Chugai, Pfizer, Santen, Tanabe-Mitsubishi, Speakers bureau: AbbVie, Actellion, Astellas, Bristol-Myers-Squibb, Chugai, Diichi-Sankyo, Eisai, Pfizer, Tanabe-Mitsubishi, Y. Kaneko Consultant for: Abbvie, Paid instructor for: Eisai Pharmaceutical, Chugai Pharmaceutical, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, Speakers bureau: Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, Janssen, UCB, A. Kawakami Grant/research support from: Abbvie GK, Eisai Co., Mitsubishi Tanabe Pharma Co., Pfizer Japan, Janssen Pharmaceutical K. K., Takeda Pharmaceutical Company, Astellas Pharma Inc., Santen Pharmaceutical Co., Bristol-Myers Squibb, ONO Pharmaceutical Co., Chugai Pharmaceutical Co., Taisho Toyama Pharmaceutical Co., Speakers bureau: Abbvie GK, Eisai Co., Mitsubishi Tanabe Pharma Co., Pfizer Japan, Janssen Pharmaceutical K. K., Takeda Pharmaceutical Company, Astellas Pharma Inc., Santen Pharmaceutical Co., Bristol-Myers Squibb, ONO Pharmaceutical Co., Chugai Pharmaceutical Co., Taisho Toyama Pharmaceutical Co., T. Matsui: None declared, R. Sakai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis KK., Santen Pharmaceutical Co., Ltd., Sekisui Medical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., and UCB Japan, R. Koike: None declared, N. Miyasaka Grant/research support from: Abbott Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Dainihon-Sumitomo Pharma Co. Ltd., Daiichi-Sankyo Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Co., Novartis Pharma K.K., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd, Consultant for: Abbott Japan Co., Ltd., Bristol Myers Squibb, Janssen Pharmaceutical KK, and Otsuka Pharmaceutical Co. Ltd., M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals,　Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, Consultant for: Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical KK, Teijin Pharma Ltd.

DOI: 10.1136/annrheumdis-2015-eular.2103

 

 

背景: 在RA目标治疗策略(T2T)中[1], 简化的疾病活动指数(SDAI)已被提出作为临床缓解评判标准之一[2]。临床试验已经揭示SDAI缓解对关节功能和结构未来演变的预测能力, 但还没有在常规诊疗实践T2T的队列研究中得到证实。

目的: 探究获得SDAI缓解是否能预测T2T队列未来获得良好的关节功能和结构结局。

方法: T2T流行病学研究是一项多中心、前瞻性队列研究, 纳入中重度活动的RA患者, 按照T2T策略治疗72周。每12周评估疾病活动度, 并据之调整治疗。主要观察中的是治疗72周时的HAQ和ΔmTSS在。利用多变量逻辑回归分析检验第24周SDAI缓解与主要观察终点之间的相关性。使用多重插补法处理缺失数据。多重比较时应用错误发现率(False Discovery Rate)和BH方法校正统计学显著性水平。

结果: 共招募318名患者, 其中244例患者随访了72周并进行分析。患者特征如下, 女性77％, 平均年龄61岁, 平均病程57个月。第24周时SDAI缓解达标率为33%。第72周时, SDAI缓解达标率为50％, 61％达到HAQ缓解(HAQ≤0.5), 73％患者ΔmTSS<最小可检测变化(SDC)。与第72周时HAQ缓解显著相关的因子(比值比(95％CI)包括Steinbrocker分期为I期[2.35(1.23-4.46), P=0.009]、基线H​​AQ [0.30(0.19-0.47), P=2.4x10^-7]、无RA相关关节置换史 [9.90(1.57-62.5), P=0.015]以及24周时达到SDAI临床缓解 [3.24(1.57-6.71), P=0.0015]。与ΔmTSS

结论: 对常规诊疗实践T2T策略的队列而言, 第24周获得SDAI缓是未来在第72周时获得关节功能和结构的良好结局的显著预测因子。

Table 1. Factors associated with HAQ≤0.5 at week 72

Variable	Odds Ratio (95%CI)	p value
(Intercept)	35.53 (7.21-175.01)	1.14E-5
Age	0.98 (0.96-1.00)	0.089
Steinbrocker's stage I (vs. stage II III IV)	2.35 (1.23-4.46)	0.009*
No history of joint replacement	9.90 (1.57-62.50)	0.015*
HAQ at enrollment	0.30 (0.19-0.47)	2.38E-7*
SDAI remission at week 24	3.24 (1.57-6.71)	0.0015*

   

Table 2. Factors associated with ΔmTSS

Variable	Odds Ratio (95%CI)	p value
(Intercept)	6.19 (3.25-11.81)	3.24E-8
Steinbrocker's stage I (vs. stage II III IV)	2.82 (1.40-5.65)	0.0037*
Number of DMARDs used before enrollement	0.79 (0.62-1.00)	0.054
Serum MMP-3 level at week 24	0.998 (0.996-1.000)	0.035*
SDAI remission at week 24	3.21 (1.46-7.02)	0.0036*

 *The p value was statistically significant after correction for multiple comparison using FDR and BH methods.

 

表1. 与第72周HAQ≤0.5相关的因子

变量	比值比 (95%CI)	P值
(截距)	35.53 (7.21-175.01)	1.14E-5
年龄	0.98 (0.96-1.00)	0.089
Steinbrocker分期为I (与分期II、 III和IV相比)	2.35 (1.23-4.46)	0.009*
无关节置换史	9.90 (1.57-62.50)	0.015*
招募时HAQ评分	0.30 (0.19-0.47)	2.38E-7*
第24周获得SDAI缓解	3.24 (1.57-6.71)	0.0015*

   

表2. 与第72周ΔmTSS

变量	比值比 (95%CI)	P值
(截距)	6.19 (3.25-11.81)	3.24E-8
Steinbrocker分期为I (与分期II、 III和IV相比)	2.82 (1.40-5.65)	0.0037*
招募前使用过DMARDs的种类数	0.79 (0.62-1.00)	0.054
第24周MMP-3血清水平	0.998 (0.996-1.000)	0.035*
第24周获得SDAI缓解	3.21 (1.46-7.02)	0.0036*

 *: 用FDR和BH方法校正的多重比较分析达到统计学显著意义的p值。