江西多乐彩11选5

學術進展

您的位置:首頁--新聞中心--學術進展

2012 ACR進展——建立和驗證多個以DAS28為基礎的類風濕關節炎復發標準

發布時間:2012-12-28 12:47:56

背景/目的:為了能穩定評估藥物減量、撤藥和劑量優化策略對臨床的影響,類風濕關節炎(RA)臨床研究中越來越需要一個確切有效能評價疾病復發的指標。已有多個以DAS28為基礎的復發標準,但都未經驗證。

方法:我們選擇3個縱向觀測數據庫,包括因RA惡化撤藥或改變治療的患者來測試以往發表的以DAS28為基礎的復發標準,是否符合標準構建效度的5個假設。已發表的DAS28復發標準為:1 ] DAS28增加值 > 1.2,或DAS28 > 5.1時增加> 0.6;2 ] DAS28增加值 > 1.2,或DAS28≥3.2時增加> 0.6;3 ]DAS增加> 0.6或DAS28 > 3.2;4 ] DAS28 增加> 1.2;5 ] DAS28 > 3.2;6 ] DAS 28 > 2.6。用于評估有效性的5個假設為:A+B)與RA惡化評估中病人/醫生的總體評價相比,敏感性和特異性> 70% ; C)DMARD/類固醇激素開始或增加的比例> 0.2,D) C反應蛋白均值變化> 10 mg /l,和E)符合復發標準的與不符合的患者相比,SF36心理健康(MH)指標變化沒有統計學上差異。檢測靈敏度/特異性,卡方和雙樣本student’s T檢驗。

結果:3個研究中分別有51、147和744例RA患者納入本研究。兩項研究中患者接受英夫利昔治療,其中較大的一項研究(NOR-DMARD)還包括新合成或生物DMARD治療的患者。基線特征見表1。標準2(DAS28增加值 > 1.2,DAS28≥3.2時DAS28增加> 0.6)符合大多數預定的假設(5項中的4項,表2)。敏感性和特異性分別介于63 - 78%和84 - 92%。建構效度結果表明23%以上的個治療變化、較高的?CRP(11.4mg/l)和 SF – 36 MH只減少 5。標準3,5和6敏感高較高,而標準1,2和4則特異性較高。

結論:DAS28增加值 > 1.2,或DAS28≥3.2時增加> 0.6似乎是最嚴格的標準并得到預定指標。不同的DAS28為基礎的復發標準,敏感性和特異不同,可能是因為各自為特定研究所選擇的參數不同。 該標準對疾病惡化程度的影響有待進一步的評價,同樣還需要更多的數據來改進它。

原文:

Construct and Criterion Validity of Several Proposed DAS28 Based Rheumatoid Arthritis Flare Criteria: A Cohort Validation Study

Abstract#: 2609
Presenter: Aatke van der Maas: Sint Maartenskliniek
Date: Wednesday, November 14

Background/Purpose: To enable consistent assessment of impact of tapering, withdrawal and dose optimization strategies, there is an increasing need for validated measures of flare in rheumatoid arthritis (RA) clinical studies. Several DAS28 based flare criteria have been described, but none validated

Methods: We used 3 longitudinal observational databases that included treatment withdrawal or change in relation to RA worsening to test 6 previously published DAS28 based flare criteria on fulfilment of 5 hypotheses concerning criterion and construct validity. Published DAS28 based flare criteria were: 1] an increase in DAS28>1.2, or >0.6 if current DAS28>5.1, 2] an increase in DAS28>1.2, or >0.6 if DAS28≥3.2, 3] an increase>0.6 or DAS28>3.2, 4] an increase in DAS28>1.2, 5] DAS28 >3.2, 6] DAS28 >2.6. The 5 hypotheses used to assess validity were: A+B) Sensitivity and specificity >70% compared to patient|s/physician|s judgment of RA worsening assessed with a transition question, and C) difference in proportion with DMARD/corticosteroid initiation/increase >0.2, D) difference in mean CRP change >10mg/L, and E) no statistical difference in SF36 Mental Health (MH) subscale change in patients fulfilling versus not fulfilling the flare criteria. Sensitivity/specificity, Chi square and two sample student|s T test were done

Results: Analyses included 51, 147 and 744 RA patients in the 3 studies. Two studies included patients treated with infliximab and the larger study (NOR-DMARD) included patients initiating a new synthetic or biologic DMARD. Baseline characteristics are described in Table 1. Criterion 2 (an increase in DAS28>1.2, or >0.6 if DAS28≥3.2) fulfilled most predefined hypotheses (4 out of 5, Table 2). Sensitivity and specificity for criterion 2 varied between 63 - 78% and 84 - 92%, respectively. Construct validity was demonstrated with 23% more treatment change, a higher mean ?CRP (11.4 mg/L) and a difference in ?SF-36 MH of only -5. Criteria 3, 5 and 6 tended to be more sensitive, criteria 1, 2 and 4 more specific .

Conclusion: An increase in DAS28>1.2, or >0.6 if DAS28≥3.2 appears most discriminating and valid by our predefined criteria. The differences in sensitivity and specificity between the various DAS28-based flare criteria may be of importance for selection of flare criteria for specific studies. Further assessment, with evaluation of impact relative to levels of worsening, in additional databases may refine criteria

Table 1 Baseline characteristics - mean (SD) unless otherwise noted    

Database123
Number of patients51147744
Age, years59 (11.2)58 (12)56 (13.5)
Female, No (%)29 (57)101 (69)539 (72)
Disease duration in years14 (7.5)11 (7)6.4 (9.5)
RF positive, No (%)42 (82)117 (81)496 (68)
Anti-CCP positive, No (%)37 (73)95 (69)146 (70)
DAS28 at inclusion2.5 (0.7)3.5 (1.3)5.2 (1.1)
DAS28 at 3 months after inclusion  3.4 (1.2)*
No. of previous DMARDs, median [p25-p75]3 [2-3]3 [2-3]

0 [0-2]

Table 2 Fulfilment of DAS28 based flare criteria on 5 hypotheses regarding construct and criterion validity

 

 Criterion validity: databases 1 and 2Construct validity: database 3
Flare criteriaHypothesis 1Hypothesis 2Hypothesis 3Hypothesis 4Hypothesis 5
In patients classified as a having a flare:Sens/spec patient >70% compared to transition scaleSens/spec physician >70% compared to transition scaleHigher proportion of DMARD/corticosteroid change (>0.2)Higher CRP     No change in depression (≤5 points in MH scale)
(>10 mg/L)
 Sens*Spec*Sens*Spec*Proportion difference**CRP difference mg/L (SE)***MH difference (SE)
%%%%
1) ΔDAS28 > 1.2 or > 0.6 if DAS28>5.146/5695/9253/7895/920.2813.1 (2.2)-6.1 (1.4)
2) ΔDAS28> 1.2 or > 0.6 if DAS28>3.269/6392/8473/7892/860.2311.4 (1.7)-5.0 (1.2)
3)  ΔDAS28> 0.6 or a DAS28>3.298/9470/61100/8967/600.163.7 (1.2)-2.8 (1.0)
4)  ΔDAS28>1.246/5696/9351/7895/920.2713.0 (2.3)-6.6 (1.4)
5) reaching DAS28>3.291/8878/6791/8976/680.183.1 (1.2)-2.6 (1.0)
6)  reaching DAS28 > 2.698/9455/46100/8953/470.132.4 (1.0)-3.2 (1.1)
*Sens=sensitivity, Spec= specificity. Results from database1 / database2 are represented on sensitivity and specificity. ** All proportion differences are statistically significant, with p<0.0001.*** All differences in CRP are statistically significant, with at least p<0.05  

Aatke van der Maas1, Elisabeth Lie2, Robin Christensen3, Ernest Choy4, Ya?l A. de Man5, Piet L.C.M. van Riel6, Thasia G. Woodworth7 and Alfons A. den Broeder1, 1Sint Maartenskliniek, Nijmegen, Netherlands, 2Diakonhjemmet Hospital, Oslo, Norway, 3Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital, Copenhagen, Denmark, 4Cardiff University School of Medicine, Cardiff, United Kingdom, 5Erasmus Medical Centre, Rotterdam, Netherlands, 6Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 7Visiting Clinical Researcher, Geffen School of Medicine, UCLA, Los Angeles, CA

本網站部分資源來源于網絡,版權歸原作者所有,轉載僅作交流。

 

 

< 返回

Copyright  2012-2014  河南百年康鑫藥業有限公司  All Rights Reserved

地址:武漢市東湖高新區高新大道666號人福醫藥集團3樓

電話:027-87596108 傳真:027-87596009


江西多乐彩11选5