Yan D, Zheng W J
Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China.
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2020 Dec 18;52(6):1166-1170. doi: 10.19723/j.issn.1671-167X.2020.06.032.
Behcet syndrome (BS) is a chronic systemic inflammatory disorder involving vessels of all sizes, characterized by relapsing episodes of oral and/or genital ulcers, as well as skin lesions. Ocular, vascular, gastrointestinal, neurological system involvement can cause significant morbidity and mortality. Glucocorticoids and immunosuppressants are the cornerstones for the management of BS. Biologic agents has been recommended for severe and/or refractory BS. Interferon-α (IFN-α) had multiple biological effects, such as antiviral and antiproliferative, that could regulate both innate and adaptive immunity in BS. Growing evidence showed the efficacy of IFN-α in severe and/or refractory BS. Many studies have demonstrated that IFN-α has comparable effectiveness and tolerance profiles as anti-tumor necrosis factor (TNF) agents for Behcet's uveitis with a much lower cost and steroid-and immunosuppressant-sparing effects. IFN-α has been recommended as second-line therapy for ocular involvement of BS in EULAR (The European League Against Rheumatism) 2018. IFN-α also improves mucocutaneous lesions in BS with the dosage from 3 to 9-12 million IU three times per week. A few cases indicated the therapeutic potential of IFN-α in intestinal BS. As a new trial of IFN-α in vascular BS (VBS), a recent study revealed the lower relapse rate and higher recanalization rate with IFN-α in lower extremity deep vein thrombosis (DVT). Another two case reports presented the efficacy of IFN-α in pulmonary artery involvement in BS. Also, case reports have shown successful treatment in refractory neurological involvement. There are two subtypes of IFN-α commonly used in autoimmune diseases, named IFN-α2a and IFN-α2b. IFN-α2a seemed more effective than IFN-α2b, especially in ocular and mucocutaneous involvement of BS. Side effects of IFN-α are dose-dependent and not severe. The most frequent side effects are flu-like syndrome, mild leukopenia and alopecia. Considering the potential risk of tuberculosis (TB) and hepatitis B virus (HBV) reactivation of TNF-α inhibitors, IFN-α is safe due to its anti-HBV effect and protective effect on TB. In conclusion, IFN-α is a promising choice for severe and/or refractory BS patients, especially for those who are intolerant or contraindicant to other biological agents, such as TNF inhibitors. Further prospective controlled studies are warranted to confirm the efficacy and safety of IFN-α in BS.
白塞病(BS)是一种慢性全身性炎症性疾病,累及各种大小的血管,其特征为口腔和/或生殖器溃疡以及皮肤病变反复发作。眼部、血管、胃肠道、神经系统受累可导致严重的发病率和死亡率。糖皮质激素和免疫抑制剂是白塞病治疗的基石。生物制剂已被推荐用于重度和/或难治性白塞病。干扰素-α(IFN-α)具有多种生物学效应,如抗病毒和抗增殖作用,可调节白塞病中的固有免疫和适应性免疫。越来越多的证据表明IFN-α在重度和/或难治性白塞病中具有疗效。许多研究表明,IFN-α与抗肿瘤坏死因子(TNF)药物治疗白塞氏葡萄膜炎的有效性和耐受性相当,但其成本低得多,且具有节省类固醇和免疫抑制剂的作用。在2018年欧洲抗风湿病联盟(EULAR)中,IFN-α被推荐作为白塞病眼部受累的二线治疗药物。IFN-α还可改善白塞病的黏膜皮肤病变,剂量为每周三次,每次3至900 - 1200万国际单位。少数病例表明IFN-α在肠道白塞病中具有治疗潜力。作为IFN-α治疗血管性白塞病(VBS)的一项新试验,最近一项研究显示,在下肢深静脉血栓形成(DVT)中,IFN-α可降低复发率并提高再通率。另外两篇病例报告展示了IFN-α治疗白塞病肺动脉受累的疗效。此外,病例报告显示其在难治性神经系统受累方面治疗成功。在自身免疫性疾病中常用的IFN-α有两种亚型,即IFN-α2a和IFN-α2b。IFN-α2a似乎比IFN-α2b更有效,尤其是在白塞病的眼部和黏膜皮肤受累方面。IFN-α的副作用与剂量相关且不严重。最常见的副作用是流感样综合征、轻度白细胞减少和脱发。考虑到TNF-α抑制剂有结核(TB)和乙型肝炎病毒(HBV)重新激活的潜在风险,IFN-α因其抗HBV作用和对TB的保护作用而安全。总之,IFN-α对于重度和/或难治性白塞病患者是一个有前景的选择,尤其是对于那些对其他生物制剂(如TNF抑制剂)不耐受或禁忌的患者。有必要进行进一步的前瞻性对照研究以证实IFN-α在白塞病中的疗效和安全性。