Division of Genetics and Molecular Medicine, King's College London, London, SE1 9RT, UK.
Br J Dermatol. 2013 Aug;169(2):306-13. doi: 10.1111/bjd.12341.
A substantial proportion of patients with psoriasis do not respond, or lose initial response to tumour necrosis factor-α antagonists. One possible mechanism relates to subtherapeutic drug levels due to an immunogenic antibody response.
To investigate the association between serum adalimumab and etanercept levels, antidrug antibody levels and clinical response in a cohort of patients with psoriasis using a commercially available enzyme-linked immunoassay.
In a single-centre cohort of 56 adults with chronic plaque psoriasis initiated on adalimumab or etanercept monotherapy between 2009 and 2011, drug and antidrug antibody levels were measured at the patients' routine clinic reviews (4, 12 and 24 weeks of treatment and the last available observation). Patients' responses at 6 months were stratified into responders [75% reduction in Psoriasis Area and Severity Index from baseline (PASI 75) or Physician's Global Assessment score of 'clear' or 'nearly clear'] and nonresponders (failure to achieve PASI 50).
After 4 weeks, adalimumab levels were significantly higher in responders compared with nonresponders (P = 0·003) and these higher levels were sustained at 12 and 24 weeks. Anti adalimumab antibodies were detected in 25% of nonresponders (two of eight patients, average 22·5 weeks' follow-up) and none of the responders (n = 23, average 26·1 weeks' follow-up). There was no significant association between etanercept levels and clinical response at 4 weeks (P = 0·317) and no antietanercept antibodies were detected. Lack of serum trough levels may have resulted in underestimation of the prevalence of antidrug antibodies.
Early adalimumab drug level monitoring at 4 weeks may be useful in predicting treatment response and potentially reduce drug exposure (and associated cost) with earlier review of treatment in those with low levels. No conclusions about the value of etanercept drug monitoring can be made due to the paucity of data. Larger studies are now required to assess the clinical utility and cost-effectiveness of these assays in personalizing therapy in psoriasis.
相当一部分银屑病患者对肿瘤坏死因子-α拮抗剂无应答或初始应答丧失。一种可能的机制与由于免疫原性抗体反应导致的治疗性药物水平降低有关。
本研究旨在使用市售酶联免疫吸附试验(ELISA),调查银屑病患者队列中血清阿达木单抗和依那西普水平、抗药物抗体水平与临床应答之间的关系。
在 2009 年至 2011 年期间接受阿达木单抗或依那西普单药治疗的 56 例慢性斑块状银屑病成人患者的单中心队列中,在患者常规临床复查时(治疗第 4、12 和 24 周及最后一次可获得的观察时)测量药物和抗药物抗体水平。根据 6 个月时的应答情况,将患者分为应答者(从基线起银屑病面积和严重性指数[PASI]改善 75%[PASI 75]或医生整体评估评分“清除”或“几乎清除”)和无应答者(未达到 PASI 50)。
治疗 4 周后,应答者的阿达木单抗水平明显高于无应答者(P = 0.003),并且在 12 周和 24 周时仍保持较高水平。在 25%的无应答者(8 例患者中的 2 例,平均随访 22.5 周)中检测到抗阿达木单抗抗体,而在所有应答者(n = 23,平均随访 26.1 周)中均未检测到。在治疗第 4 周时,依那西普水平与临床应答之间无显著关联(P = 0.317),也未检测到抗依那西普抗体。由于缺乏血清谷浓度值,可能低估了抗药物抗体的发生率。
在治疗第 4 周时早期监测阿达木单抗药物水平可能有助于预测治疗反应,并可能通过更早地评估治疗来降低药物暴露(并降低相关成本),从而使那些药物水平较低的患者受益。由于数据有限,尚不能得出关于依那西普药物监测价值的结论。现在需要更大规模的研究来评估这些检测在银屑病患者个体化治疗中的临床实用性和成本效益。