Predictors of response to anti-TNF-α therapy among patients with rheumatoid arthritis:: results from the British Society for Rheumatology Biologics Register
Predictors of response to anti-TNF-α therapy among patients with rheumatoid arthritis:: results from the British Society for Rheumatology Biologics Register
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DOI：
10.1093/rheumatology/kel149
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发表时间：
2006-12-01
期刊：
影响因子：
5.5
通讯作者：
Symmons, D. P. M.
中科院分区：
文献类型：
--
作者：
Hyrich, K. L.;Watson, K. D.;Symmons, D. P. M.
背景抗肿瘤坏死因子-α（TNF-α）疗法代表了类风湿性关节炎（RA）治疗的重要进展。然而，仍有一部分患者尽管接受治疗，但病情并未改善。这些药物价格昂贵，并且具有严重的毒性。因此，理想的情况是预测哪些患者会有反应，以便有针对性地使用这些药物。确定RA患者在抗TNF-α治疗开始时与6个月应答相关的临床因素。英国风湿病学会（BSR）生物制剂登记处收集了英国所有接受生物治疗的风湿性疾病患者的详细数据。我们研究了所有开始使用依那西普（ETA）或英夫利昔单抗（INF）治疗的RA患者，并在2004年10月1日之前完成了至少6个月的随访。使用疾病活动性评分（DAS 28）评估基线和6个月时的疾病状态。根据欧洲反风湿联盟（EULAR）改善标准对缓解进行分类。基线特征对应答的影响采用多变量有序逻辑回归进行研究。2879例患者纳入本分析（1267例ETA，1612例INF）。在治疗开始时，平均年龄为55岁，疾病持续时间为14年，基线DAS 28为6.7，健康评估问卷（HAQ）为2.1。总的来说，28%的ETA患者和86%的INF患者接受了甲氨蝶呤治疗。6个月后，18%有良好的EULAR反应，其中9%被认为是在缓解和50%有中度反应。两种抗TNF-α治疗之间的缓解率没有总体差异。较高的基线HAQ评分与较低的缓解率相关，而较好的缓解与当前使用NSAID和使用甲氨蝶呤（MTX）相关，尽管后者仅在ETA时达到统计学显著性[OR 1.82（95% CI 1.38-2.40）]。目前吸烟者的缓解率较低，尤其是接受INF治疗的患者[OR 0.77（95% CI 0.60-0.99）]。年龄，病程，类风湿因子和以前的疾病缓解抗风湿药物（DMARDs）的数量不能预测对任何一种药物的反应。然而，女性不太可能达到缓解。这些数据支持接受MTX联合抗TNF-α治疗的患者结局改善。然而，大多数残疾患者不太可能响应，尽管并发MTX。NSAID的获益可能反映了能够耐受这些药物的患者相对没有合并症或持续存在可逆性炎症症状。吸烟与INF不良结局的相关性是一个新发现，可能反映了药代动力学的改变。其他基线疾病特征无法预测结果表明，其他因素，包括药物代谢的潜在遗传差异，可能影响抗TNF-α治疗的反应。
Background. Anti-tumour necrosis factor-alpha (TNF-alpha) therapies represent an important advancement in therapy for rheumatoid arthritis (RA). However, there remains a proportion of patients who do not improve despite therapy. These drugs are expensive and have the potential of serious toxicity. Therefore, it would be ideal to predict the patients who will respond, so that the use of these drugs can be targetted.Objective. To identify the clinical factors present at the start of anti-TNF-alpha therapy that are associated with response at 6 months in patients with RA.Methods. The British Society for Rheumatology (BSR) Biologics Register collects detailed data on all patients with a rheumatic disease receiving biologic therapy in the UK. We studied all patients with RA who had started etanercept (ETA) or infliximab (INF) and had achieved a minimum 6 months follow-up by 1 October, 2004. The disease status at the baseline and at 6 months was assessed using the Disease Activity Score (DAS28). The response was classified according to the European League against Rheumatism (EULAR) improvement criteria. The effect of baseline characteristics on response was studied using multivariate ordinal logistic regression.Results. 2879 patients were included in this analysis (1267 ETA, 1612 INF). At the start of therapy, the mean age was 55 yrs, disease duration 14 yrs, baseline DAS28 6.7 and health assessment questionnaire (HAQ) 2.1. In all, 28% of ETA and 86% of INF patients were receiving methotrexate. After 6 months, 18% had a good EULAR response, of whom 9% were considered to be in remission and 50% had a moderate response. There was no overall difference in response rate between the two anti-TNF-alpha therapies. A higher baseline HAQ score correlated with a lower response rate while a better response was associated with the current use of NSAIDs and the use of methotrexate (MTX), although the latter only reached statistical significance with ETA [OR 1.82 (95% CI 1.38-2.40)]. There was a lower response rate among current smokers, particularly in patients receiving INF [OR 0.77 (95% CI 0.60-0.99)]. Age, disease duration, rheumatoid factor and the previous number of disease-modifying antirheumatic drugs (DMARDs) did not predict response to either drug. However, females were less likely to achieve remission.Conclusions. These data support an improved outcome among patients receiving MTX in combination with anti-TNF-alpha therapies. However, the most disabled patients were less likely to respond, despite concurrent MTX. The benefits of NSAIDs may reflect the relative absence of comorbidities in patients who can tolerate these drugs or the continuing presence of reversible inflammatory symptoms. The association of smoking and poor outcome with INF is a novel finding and may reflect alterations in pharmacokinetics. The inability of other baseline disease characteristics to predict the outcome suggests that other factors, including potential genetic differences in drug metabolism, may be influencing the response to anti-TNF-alpha therapies.