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斑块状银屑病患者中抗阿达木单抗抗体形成的程度及临床后果。

Extent and clinical consequences of antibody formation against adalimumab in patients with plaque psoriasis.

作者信息

Lecluse Lidian L A, Driessen Rieke J B, Spuls Phyllis I, de Jong Elke M G J, Stapel Steven O, van Doorn Martijn B A, Bos Jan D, Wolbink Gert-Jan

机构信息

Department of Dermatology, Academic Medical Center, University of Amsterdam, Room A0-252, PO Box 22700, 1100 DE Amsterdam, the Netherlands.

出版信息

Arch Dermatol. 2010 Feb;146(2):127-32. doi: 10.1001/archdermatol.2009.347.

Abstract

OBJECTIVES

To investigate the extent antibodies to adalimumab are formed in patients with plaque psoriasis and whether these antibodies have clinical consequences. Also, to examine the relationship between antibodies to adalimumab and adalimumab trough titers.

DESIGN

Prospective observational cohort study.

SETTING

Two Dutch dermatology departments in university hospitals.

PATIENTS

All consecutive patients starting a regimen of adalimumab for chronic plaque psoriasis. Patients were screened and fulfilled the Dutch reimbursement criteria for adalimumab to treat psoriasis.

INTERVENTION

Adalimumab treatment (per label).

MAIN OUTCOME MEASURES

The titer of antibodies to adalimumab, the adalimumab trough concentration, and the Psoriasis Area and Severity Index at weeks 12 and 24.

RESULTS

Antibodies to adalimumab were detected in 13 of 29 patients (45%) during 24 weeks of treatment. Differences in response rates among patients with low, high, and no titers of antibodies to adalimumab were significant at weeks 12 and 24 (P = .04 and P < .001, respectively). The median adalimumab trough concentrations varied significantly among patients with low, high, and no titers of antibodies to adalimumab (1.30 [range, 0.01-5.50], 0.0 [range, 0.0-0.0], and 9.6 [range, 0.0-22.6] mg/L, respectively; P < .001). At week 24, the median adalimumab trough concentrations also differed significantly among good responders, moderate responders, and nonresponders (9.7 [range, 0.0-22.6], 8.9 [range, 3.2-12.6], and 0.0 [range, 0.0-13.3] mg/L, respectively; P = .01).

CONCLUSION

Antibodies to adalimumab are associated with lower serum adalimumab trough concentrations and with nonresponse or loss of response to adalimumab in patients with plaque psoriasis.

摘要

目的

调查斑块状银屑病患者中抗阿达木单抗抗体的形成程度,以及这些抗体是否具有临床后果。同时,研究抗阿达木单抗抗体与阿达木单抗谷浓度之间的关系。

设计

前瞻性观察队列研究。

地点

荷兰两所大学医院的皮肤科。

患者

所有开始接受阿达木单抗治疗慢性斑块状银屑病的连续患者。患者经过筛查并符合荷兰阿达木单抗治疗银屑病的报销标准。

干预措施

阿达木单抗治疗(按说明书)。

主要观察指标

治疗24周时抗阿达木单抗抗体滴度、阿达木单抗谷浓度以及第12周和第24周的银屑病面积和严重程度指数。

结果

29例患者中有13例(45%)在24周治疗期间检测到抗阿达木单抗抗体。抗阿达木单抗抗体滴度低、高和无抗体的患者在第12周和第24周的缓解率差异显著(分别为P = 0.04和P < 0.001)。抗阿达木单抗抗体滴度低、高和无抗体的患者中,阿达木单抗谷浓度中位数差异显著(分别为1.30[范围,0.01 - 5.50]、0.0[范围,0.0 - 0.0]和9.6[范围,0.0 - 22.6]mg/L;P < 0.001)。在第24周时,治疗反应良好者、中度反应者和无反应者的阿达木单抗谷浓度中位数也有显著差异(分别为9.7[范围,0.0 - 22.6]、8.9[范围,3.2 - 12.6]和0.0[范围,0.0 - 13.3]mg/L;P = 0.01)。

结论

抗阿达木单抗抗体与斑块状银屑病患者血清阿达木单抗谷浓度降低以及对阿达木单抗无反应或反应丧失有关。

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