Circulating cell-free DNA levels in Portuguese patients with psoriasis vulgaris according to severity and therapy
Circulating cell-free DNA levels in Portuguese patients with psoriasis vulgaris according to severity and therapy
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DOI：
10.1111/bjd.12738
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发表时间：
2014-04-01
影响因子：
10.3
通讯作者：
Santos-Silva, A.
中科院分区：
文献类型：
--
作者：
Coimbra, S.;Catarino, C.;Santos-Silva, A.
背景目前用生物制剂治疗银屑病已产生显著的治疗效果，尽管这些药物的疗效偶尔会降低。负责这种衰减的主要因素之一是归因于抗药抗体（ADAs）的发展。ObjectivesTo分析血清药物浓度之间的关系，存在的ADAs和阿达木单抗和英夫利昔单抗的治疗效果，并确定最佳使用这些biologics.MethodsThis是一个为期1年的前瞻性研究在皮肤科的科比大学医院和合作医院。纳入了开始阿达木单抗和英夫利西单抗治疗银屑病方案的所有患者。我们测量的药物和抗体的阿达木单抗和英夫利昔单抗，以及在第0周，4，12，24和48周的Pszymus面积和严重程度指数分数的血清浓度在第一年的treatment.ResultsWe观察到50%的阿达木单抗的ADA阳性率，和41%的ADA阳性率英夫利昔单抗。ADA滴度从低到高变化范围较宽。在高滴度组中，患者表现出降低的临床应答，并证明滴度与临床应答之间呈负相关。然而，在低滴度组和未检测到阿达木单抗抗体的组之间观察到等效的治疗效果。对于英夫利西单抗，ADA患者的临床应答降低。观察到抗体产生与临床反应降低之间存在明显的负相关性。结论阿达木单抗和英夫利西单抗这两种生物制剂表现出不同的治疗行为。ADA和药物浓度的测量对生物制剂的治疗有重要意义。关于这个主题，我们已经知道些什么？在接受生物制剂治疗的患者中观察到抗药抗体（ADA）的高频率产生，这种产生已导致治疗效果受损。本研究补充了什么？生物制剂的最佳使用应通过测量每例患者的ADA和每种药物浓度来确定，因为标准方案可能不适用于所有患者。
BackgroundCurrent treatment with biologics has produced dramatic therapeutic effects in patients with psoriasis, although these agents occasionally decrease in efficacy. One of the main factors responsible for this attenuation is attributed to the development of antidrug antibodies (ADAs).ObjectivesTo analyse the relationship between serum drug concentrations, the presence of ADAs and treatment efficacy of adalimumab and infliximab, and to determine the optimal use of these biologics.MethodsThis was a 1-year prospective study in the dermatology departments of Kobe University Hospital and collaborating hospitals. All patients starting a regimen of adalimumab and infliximab for psoriasis were included. We measured the serum concentration of the drugs and titres of antibodies to adalimumab and infliximab, as well as the Psoriasis Area and Severity Index scores at weeks 0, 4, 12, 24 and 48 during the first year of treatment.ResultsWe observed a 50% positive rate of ADAs to adalimumab, and a 41% positive rate of ADAs to infliximab. The titres of ADAs showed a wide range from low to high titres. In the high-titre groups, the patients exhibited a decreased clinical response, and demonstrated a negative correlation between titre and clinical response. However, an equivalent therapeutic effect was observed between the low-titre group and the group with no antibodies detected for adalimumab. For infliximab, the patients with ADAs showed decreased clinical response. An apparent negative correlation between antibody production and reduced clinical response was observed.ConclusionsTwo biologics, adalimumab and infliximab, showed different therapeutic behaviour. The measurement of ADAs and drug concentrations has important implications for treatment with biologics.What's already known about this topic? High frequent production of antidrug antibodies (ADAs) has been observed in patients treated with biologics, and the production has caused impairment of treatment efficacy.What does this study add? The optimal use of the biologics should be determined by the measurement of ADAs and each drug concentration in each patient because the standard protocol may not uniformly fit all patients.