Arida Aikaterini, Sfikakis Petros P
First Department of Propedeutic Internal Medicine Laikon Hospital, Athens University Medical School, Athens, Greece.
Clin Exp Rheumatol. 2014 Jul-Aug;32(4 Suppl 84):S149-55. Epub 2014 Sep 30.
Unmet therapeutic needs in Behçet's disease have drawn recent attention to biological agents targeting cytokines other than TNF. The anti-IL-17 antibody secukinumab and the anti-IL-2 receptor antibody daclizumab were not superior to placebo for ocular Behçet's in randomised controlled trials, comprising 118 and 17 patients, respectively. The anti-IL-1 agents anakinra and canakinumab and the anti-IL-6 agent tocilizumab were given to isolated refractory disease patients, who were either anti-TNF naïve (n=9) or experienced (n=18). No new safety signals were reported. Although a potential for bias to report positive effects and underreport negative cases may exist, Anakinra was partially effective, whereas disease remission was noted after canakinumab in some anti-TNF resistant patients. Tocilizumab appeared effective for neuro-Behçet's, but not for mucocutaneous manifestations. Finally, in a pilot study of 7 patients with relapsing posterior uveitis refractory to azathioprine and/or cyclosporine, the anti-IL-1β antibody Gevokizumab was beneficial. Collectively, it seems that IL-1 and IL-6 are promising targets in patients refractory or intolerant to other regimens including anti-TNFs. However, controlled studies are surely needed.
白塞病未满足的治疗需求最近使人们将注意力转向靶向除肿瘤坏死因子(TNF)以外细胞因子的生物制剂。在分别纳入118例和17例患者的随机对照试验中,抗白细胞介素-17(IL-17)抗体司库奇尤单抗和抗IL-2受体抗体达利珠单抗在治疗眼部白塞病方面并不优于安慰剂。抗IL-1药物阿那白滞素和卡那单抗以及抗IL-6药物托珠单抗被给予孤立的难治性疾病患者,这些患者要么未使用过抗TNF药物(n = 9),要么曾使用过抗TNF药物(n = 18)。未报告新的安全信号。尽管可能存在报告积极效果而漏报负面病例的偏倚,但阿那白滞素部分有效,而在一些抗TNF耐药患者中,卡那单抗治疗后出现了疾病缓解。托珠单抗对神经白塞病似乎有效,但对黏膜皮肤表现无效。最后,在一项针对7例对硫唑嘌呤和/或环孢素治疗无效的复发性后葡萄膜炎患者的初步研究中,抗IL-1β抗体 gevokizumab 显示出有益效果。总体而言,对于对包括抗TNF药物在内的其他治疗方案难治或不耐受的患者,IL-1和IL-6似乎是有前景的治疗靶点。然而,肯定需要进行对照研究。