St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and Division of Genetics and Molecular Medicine, King's College London, 9th Floor Guy's Tower, Great Maze Pond, London SE1 9RT, U.K.
Br J Dermatol. 2010 Apr;162(4):780-5. doi: 10.1111/j.1365-2133.2009.09563.x. Epub 2009 Oct 26.
An increasing number of patients with severe psoriasis are failing to respond to antitumour necrosis factor (TNF)-alpha therapy (etanercept, infliximab and adalimumab).
We observed that many of these patients developed antinuclear antibodies (ANA) and antidouble-stranded DNA (anti-dsDNA) antibodies while on treatment prompting us to investigate whether their development is associated with anti-TNF treatment failure.
All patients with psoriasis who had received anti-TNF therapies were identified and their blood results and treatment histories were obtained from electronic patient records and case notes.
A total of 97 patients had been treated with anti-TNF agents (60 were on their first agent, 22 had been on and stopped one agent, nine had been on and stopped two agents and six had been on and stopped all three agents). ANA developed in 17% of patients on their first treatment, 54% of patients who had failed one treatment, 78% of patients who had failed two treatments and 83% of patients who had failed all three treatments. Anti-dsDNA antibodies developed in 2%, 27%, 33% and 83% of patients from the same respective groups. Significantly, the antibodies developed before treatment had failed with all three agents and their development was not related to the total time that patients had been on anti-TNF therapy.
This study suggests that the development of ANA and anti-dsDNA antibodies on anti-TNF treatment may act as a marker of forthcoming treatment failure. Large-scale prospective studies are required to assess the importance of this observation.
越来越多的重度银屑病患者对抗肿瘤坏死因子(TNF)-α 治疗(依那西普、英夫利昔单抗和阿达木单抗)无应答。
我们观察到许多接受治疗的患者产生了抗核抗体(ANA)和抗双链 DNA(anti-dsDNA)抗体,促使我们研究其产生是否与抗 TNF 治疗失败有关。
所有接受过抗 TNF 治疗的银屑病患者均被识别,并从电子患者记录和病历中获取其血液检查结果和治疗史。
共 97 例患者接受了抗 TNF 药物治疗(60 例首次用药,22 例曾用一种药物但已停药,9 例曾用两种药物但已停药,6 例曾用三种药物但已停药)。首次治疗的患者中有 17%出现 ANA,一种药物治疗失败的患者中有 54%,两种药物治疗失败的患者中有 78%,三种药物治疗失败的患者中有 83%。从相同的相应组中,ANA 分别发展为 2%、27%、33%和 83%的患者,抗 dsDNA 抗体。重要的是,这些抗体在所有三种药物治疗失败之前就已经产生,并且其产生与患者接受抗 TNF 治疗的总时间无关。
本研究表明,抗 TNF 治疗中 ANA 和抗 dsDNA 抗体的产生可能是即将发生治疗失败的标志物。需要进行大规模前瞻性研究来评估这一观察结果的重要性。