临床疗效和非甾体抗炎药节省终点单独或联合使用在轴性脊柱关节炎中的判别能力

Discriminant Capacity of Clinical Efficacy and Nonsteroidal Antiinflammatory Drug-sparing Endpoints, Alone or in Combination, in Axial Spondyloarthritis.

作者信息

Dougados Maxime, Wood Emily, Gossec Laure, Dubanchet Arnaud, Logeart Isabelle, van der Heijde Désirée

机构信息

From the Paris Descartes University; Department of Rheumatology-Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP); Institut national de la santé et de la recherche médicale (INSERM; U1153): Clinical epidemiology and biostatistics, PRES Sorbonne Paris-Cité; Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique; Department of Rheumatology, Pitié Salpêtrière Hospital, AP-HP; Pfizer, Paris, France; Statistical Consultancy, Quanticate Ltd., Hitchin, UK; Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.M. Dougados, MD, Paris Descartes University, and Department of Rheumatology-Hôpital Cochin, AP-HP, and INSERM (U1153): Clinical epidemiology and biostatistics, PRES Sorbonne Paris-Cité; E. Wood, MSc, Statistical Consultancy, Quanticate Ltd.; L. Gossec, MD, PhD, Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, and Department of Rheumatology, Pitié Salpêtrière Hospital, AP-HP; A. Dubanchet, MD, Pfizer; I. Logeart, MD, Pfizer; D. van der Heijde, MD, PhD, Department of Rheumatology, Leiden University Medical Center.

出版信息

J Rheumatol. 2015 Dec;42(12):2361-8. doi: 10.3899/jrheum.150378. Epub 2015 Nov 15.

DOI:10.3899/jrheum.150378

PMID:26568588

Abstract

OBJECTIVE

Using data from a randomized, double-blind, placebo-controlled study, we assessed the capacity of clinical and nonsteroidal antiinflammatory drug (NSAID)-sparing endpoints, alone and in combination, to discriminate between treatment effects in axial spondyloarthritis (axSpA).

METHODS

Patients with active NSAID-resistant axSpA received etanercept (ETN) 50 mg/week or placebo for 8 weeks and tapered/discontinued NSAID. In posthoc logistic regression analyses, OR were calculated that indicated the capacity of the following endpoints to discriminate between the effects of ETN and placebo at Week 8: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50; BASDAI ≤ 3; Assessment of Spondyloarthritis international Society (ASAS) 20; ASAS40; Ankylosing Spondylitis Disease Activity Score (ASDAS) with C-reactive protein (CRP) < 1.3 and ASDAS-CRP < 2.1; ≥ 50% decrease from baseline in ASAS-NSAID score, score < 10, and score = 0; and each clinical and/or each NSAID measure.

RESULTS

In 90 randomized patients (ETN, n = 42; placebo, n = 48), disease activity was similar between groups at baseline: mean (± SD) BASDAI (ETN vs placebo) 6.0 ± 1.6 versus 5.9 ± 1.5. NSAID intake was high: ASAS-NSAID score 98.2 ± 39.0 versus 93.0 ± 23.4. OR ranged from 1.6 (95% CI 0.5-5.4) for ASDAS-CRP < 1.3 to 5.8 (95% CI 1.2-29.1) for BASDAI50 and NSAID score of 0; most measures (34/45) reached statistical significance (α = 0.05) favoring ETN. Most combined outcome variables using OR were more discriminant than single outcome measures.

CONCLUSION

These findings suggest that changes in NSAID intake during treatment do not prevent demonstration of clinically relevant effects of biologic treatment, and combined (i.e., clinical with NSAID-sparing) endpoints were frequently more discriminant than single (i.e., clinical) endpoints. ClinicalTrials.gov (NCT01298531).

摘要

目的

利用一项随机、双盲、安慰剂对照研究的数据，我们评估了临床终点和非甾体抗炎药（NSAID）节省终点单独及联合使用时，区分轴性脊柱关节炎（axSpA）治疗效果的能力。

方法

对NSAID抵抗的活动性axSpA患者，给予依那西普（ETN）50mg/周或安慰剂治疗8周，并逐渐减少/停用NSAID。在事后逻辑回归分析中，计算比值比（OR），以表明以下终点在第8周区分ETN和安慰剂效果的能力：巴斯强直性脊柱炎疾病活动指数（BASDAI）改善50%；BASDAI≤3；国际脊柱关节炎协会（ASAS）20改善；ASAS40改善；基于C反应蛋白（CRP）的强直性脊柱炎疾病活动评分（ASDAS）<1.3且ASDAS-CRP<2.1；ASAS-NSAID评分较基线降低≥50%、评分<10以及评分=0；以及每项临床和/或每项NSAID测量指标。

结果

90例随机分组患者（ETN组，n = 42；安慰剂组，n = 48），两组基线时疾病活动度相似：平均（±标准差）BASDAI（ETN组与安慰剂组）分别为6.0±1.6和5.9±1.5。NSAID摄入量较高：ASAS-NSAID评分分别为98.2±39.0和93.0±23.4。OR范围从ASDAS-CRP<1.3时的1.6（95%CI 0.5 - 5.4）到BASDAI改善50%和NSAID评分为0时的5.8（95%CI 1.2 - 29.1）；大多数指标（34/45）达到统计学显著性（α = 0.05），支持ETN。大多数使用OR的联合结局变量比单一结局指标更具鉴别力。