Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
Arthritis Res Ther. 2011 Jun 20;13(3):R94. doi: 10.1186/ar3369.
Identifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-α) blocking therapy is important, especially in view of the costs and potential side effects of these agents. Recently, the AS Disease Activity Score (ASDAS) has been developed to assess both subjective and objective aspects of AS disease activity. However, data about the predictive value of the ASDAS with respect to clinical response to TNF-α blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-α blocking therapy in AS patients in daily clinical practice.
AS outpatients who started TNF-α blocking therapy were included in the Groningen Leeuwarden Ankylosing Spondylitis (GLAS) study, an ongoing prospective longitudinal observational cohort study with follow-up visits according to a fixed protocol. For the present analysis, patients were excluded if they had previously received anti-TNF-α treatment. Predictor analyses of response and treatment discontinuation were performed using logistic and Cox regression models, respectively.
Between November 2004 and April 2010, 220 patients started treatment with infliximab (n = 32), etanercept (n = 137), or adalimumab (n = 51). At three and six months, 68% and 63% of patients were Assessments in Ankylosing Spondylitis (ASAS)20 responders, 49% and 46% ASAS40 responders, and 49% and 50% Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 responders, respectively. Baseline predictors of response were younger age, male gender, higher ASDAS score, higher erythrocyte sedimentation rate (ESR) level, higher C-reactive protein (CRP) level, presence of peripheral arthritis, higher patient's global assessment of disease activity, and lower modified Schober test. In August 2010, 64% of patients were still using their TNF-α blocking agent with a median follow-up of 33.1 months (range 2.4 to 68.2). Baseline predictors of discontinuation of TNF-α blocking therapy were female gender, absence of peripheral arthritis, higher BASDAI, lower ESR level, and lower CRP level.
Besides younger age and male gender, objective variables such as higher inflammatory markers or ASDAS score were identified as independent baseline predictors of response and/or continuation of TNF-α blocking therapy. In contrast, higher baseline BASDAI score was independently associated with treatment discontinuation. Based on these results, it seems clinically relevant to include more objective variables in the evaluation of anti-TNF-α treatment.
识别出可能从肿瘤坏死因子-α（TNF-α）阻断治疗中获益的强直性脊柱炎（AS）患者非常重要，尤其是考虑到这些药物的成本和潜在副作用。最近，AS 疾病活动评分（ASDAS）已被开发出来，用于评估 AS 疾病活动的主观和客观方面。然而，关于 ASDAS 对 TNF-α 阻断治疗临床反应的预测价值的数据尚缺乏。本研究的目的是在日常临床实践中确定 AS 患者接受 TNF-α 阻断治疗的基线预测因素。
纳入开始 TNF-α 阻断治疗的 AS 门诊患者，进行格罗宁根-吕伐登强直性脊柱炎（GLAS）研究，这是一项正在进行的前瞻性纵向观察队列研究，根据固定方案进行随访。对于本分析，排除了先前接受过抗 TNF-α 治疗的患者。使用逻辑回归和 Cox 回归模型分别进行反应和治疗终止的预测因素分析。
2004 年 11 月至 2010 年 4 月，220 例患者开始接受英夫利昔单抗（n=32）、依那西普（n=137）或阿达木单抗（n=51）治疗。在 3 个月和 6 个月时，分别有 68%和 63%的患者为 AS 评估指数（ASAS）20 应答者，49%和 46%为 ASAS40 应答者，49%和 50%为 Bath 强直性脊柱炎疾病活动指数（BASDAI）50 应答者。反应的基线预测因素为年龄较小、男性、ASDAS 评分较高、红细胞沉降率（ESR）水平较高、C 反应蛋白（CRP）水平较高、外周关节炎存在、患者疾病活动的整体评估较高，以及改良 Schober 试验较低。2010 年 8 月，64%的患者仍在使用 TNF-α 阻断剂，中位随访时间为 33.1 个月（范围 2.4-68.2）。TNF-α 阻断治疗停药的基线预测因素为女性、无外周关节炎、BASDAI 较高、ESR 水平较低和 CRP 水平较低。
除了年龄较小和男性外，客观变量如较高的炎症标志物或 ASDAS 评分被确定为反应和/或 TNF-α 阻断治疗持续的独立基线预测因素。相反，较高的基线 BASDAI 评分与治疗停药独立相关。基于这些结果，在评估抗 TNF-α 治疗时纳入更多客观变量似乎具有临床意义。
