Department of Immunology and Department of Internal Medicine, Section of Clinical Immunology, Erasmus University Medical Center Rotterdam, the Netherlands.
Allergy & Clin. Immunology, Immunomodulation & Tolerance Group, Natl Heart & Lung Inst., Inflammation Repair & Development, Imperial College, London, UK; Dept. of Pulmonology, STZ Centre of Excellence Asthma & COPD, Franciscus Group, Rotterdam, Netherland.
Clin Exp Rheumatol. 2019 Nov-Dec;37 Suppl 121(6):43-47. Epub 2019 Mar 11.
The TNF-blocker adalimumab can be effective in Behçet's disease (BD), a multisystem auto-inflammatory disorder. Unfortunately, the therapeutic efficacy of TNF-blockers can be hampered by the formation of anti-drug antibodies. We present an observational study of adalimumab in refractory BD with measurement of anti-drug antibodies.
The effect of fortnightly 40mg adalimumab in nine patients with therapy refractory mucocutaneous, non-ocular or organ threatening BD was studied up to 60 months. Primary endpoint was a decrease in disease activity, measured by the BD Current Activity Form (BDCAF) within 6 months. Secondary endpoints included serum cytokines and the long-term formation of anti-adalimumab antibodies.
BDCAF improved significantly in all nine patients from 5.4 (SD=1.4) to 2.4 (SD=1.4) (p=0.007) within one month up to 6 months and after prolonged follow up of 5 years. All patients could either taper or stop concomitant therapy. Symptoms of mucocutaneous lesions, erythema nodosum and joint involvement decreased or disappeared. Serum TNF-alpha levels were elevates in five patients and decreased upon treatment (p=0.017). Adalimumab was save and none of the patients experienced therapy failure or antibodies against adalimumab.
We present an observational study on patients with BD treated with adalimumab and provide a basis for long-term use in refractory mucocutaneous BD. These findings show that adalimumab can safely be administered yielding sustainable clinical effects in refractory BD patients with mucocutaneous disease without formation of anti-adalimumab antibodies, even after long follow up.
肿瘤坏死因子（TNF）阻滞剂阿达木单抗在贝赫切特病（BD）中可能有效，BD 是一种多系统自身炎症性疾病。不幸的是，TNF 阻滞剂的治疗效果可能会因抗药物抗体的形成而受到阻碍。我们报告了一项在难治性 BD 中使用阿达木单抗的观察性研究，并测量了抗药物抗体。
在 60 个月的时间内，我们研究了每周两次 40mg 阿达木单抗对 9 例治疗难治性黏膜皮肤、非眼部或器官威胁性 BD 的患者的疗效。主要终点是在 6 个月内通过 BD 现行活动量表（BDCAF）测量疾病活动度下降。次要终点包括血清细胞因子和长期抗阿达木单抗抗体的形成。
在 9 例患者中，BDCAF 在一个月内从 5.4（SD=1.4）显著改善至 2.4（SD=1.4）（p=0.007），并在 6 个月和 5 年的长期随访中持续改善。所有患者均能减少或停用伴随治疗。黏膜皮肤病变、结节性红斑和关节受累的症状减轻或消失。5 例患者的血清 TNF-α水平升高，治疗后降低（p=0.017）。阿达木单抗是安全的，没有患者发生治疗失败或对阿达木单抗的抗体。
我们报告了一项使用阿达木单抗治疗 BD 患者的观察性研究，为长期治疗难治性黏膜皮肤 BD 提供了依据。这些发现表明，阿达木单抗可以安全地给药，在没有形成抗阿达木单抗抗体的情况下，甚至在长期随访后，在难治性 BD 患者中具有持续的临床效果，可安全用于治疗黏膜皮肤疾病。
