First Department of Propaedeutic Internal Medicine, Laikon Hospital, and Joint Academic Rheumatology Programme, National Kapodistrian University of Athens Medical School, Athens, Greece.
Sorbonne Universités, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose Inflammatoire, Paris; INSERM, UMR_S 959, Paris, and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Clin Exp Rheumatol. 2022 Sep;40(8):1575-1583. doi: 10.55563/clinexprheumatol/avhxp6. Epub 2022 Sep 15.
Despite the remarkable efficacy of anti-TNF agents in Behçet's disease (BD), unmet therapeutic needs for refractory or intolerant patients to these drugs still exist. Based on evidence implicating IL-6 in the pathogenesis of BD, we summarise the current experience on the off-label administration of the anti-IL-6 receptor antibody tocilizumab for BD refractory to disease-modifying anti-rheumatic drugs.
We searched PubMed and EMBASE for original articles published through December 2021 reporting on the use of tocilizumab for BD.
We retrieved 25 articles fulfilling our search criteria, reporting on a total of 74 patients of whom 31 were anti- TNF naive; 2 additional anti-TNF experienced patients were included. The vast majority (72 of 76) received the standard intravenous dose of tocilizumab, whereas the total follow-up, including also post-treatment follow-up in many patients, ranged from 2 to 84 months without new safety issues. Tocilizumab was given in anti-TNF naive patients predominantly for vascular (n=16), central nervous system (n=7) and ocular involvement (n=5). On the other hand, anti-TNF experienced patients received tocilizumab predominantly for ocular (n=28), central nervous system (n=8) and mucocutaneous involvement (n=6). Tocilizumab was effective in 87% of anti-TNF naive (13 and 14 with complete and partial remission, respectively) and in 80% of anti-TNF experienced patients (17 and 19 with complete and partial remission, respectively).
Although preliminary, evidence published so far suggests that IL-6 inhibition is a legitimate therapeutic option for BD patients with refractory ocular, CNS and vascular involvement. Controlled studies are clearly needed.
尽管抗 TNF 药物在 Behçet 病(BD)中具有显著疗效,但仍有一些患者对这些药物存在难治或不耐受的情况,存在未满足的治疗需求。鉴于白细胞介素 6(IL-6)在 BD 发病机制中的作用,我们总结了目前关于使用抗 IL-6 受体抗体托珠单抗治疗对疾病修饰抗风湿药物难治的 BD 的经验。
我们在 PubMed 和 EMBASE 上搜索了截至 2021 年 12 月发表的关于托珠单抗治疗 BD 的原始文章。
我们检索到符合搜索标准的 25 篇文章,共报道了 74 例患者,其中 31 例为抗 TNF 初治患者;另外还有 2 例接受过抗 TNF 治疗的患者。绝大多数(76 例中的 72 例)患者接受了托珠单抗的标准静脉剂量,而总随访时间,包括许多患者的治疗后随访时间,从 2 到 84 个月不等,没有出现新的安全问题。在抗 TNF 初治患者中,托珠单抗主要用于治疗血管(n=16)、中枢神经系统(n=7)和眼部受累(n=5)。另一方面,接受过抗 TNF 治疗的患者接受托珠单抗主要用于治疗眼部(n=28)、中枢神经系统(n=8)和黏膜皮肤受累(n=6)。托珠单抗在抗 TNF 初治患者中的疗效为 87%(分别有 13 例和 14 例患者达到完全缓解和部分缓解),在抗 TNF 治疗患者中的疗效为 80%(分别有 17 例和 19 例患者达到完全缓解和部分缓解)。
尽管目前证据还初步,但已发表的证据表明,IL-6 抑制是治疗难治性眼部、中枢神经系统和血管受累 BD 患者的一种合理治疗选择。显然需要进行对照研究。