英利昔单抗单一疗法治疗银屑病关节炎时的细胞因子情况

作     者：Mastroianni A. Minutilli E. Mussi A. E. Berardesca 刘艳 

作者机构：Dr. Clinical Dermatology San Gallicano Dermatological Institute Via Chianesi 53 Rome Italy 

出 版 物：《世界核心医学期刊文摘（皮肤病学分册）》 (Digest of the World Core Medical JOurnals:Dermatology)

年 卷 期：2005年第1卷第12期

页      面：40-41页

学科分类：1002[医学-临床医学] 10[医学] 100206[医学-皮肤病与性病学] 

主　　题：银屑病关节炎 英利昔单抗 细胞因子 PASI 皮损面积 血浆水平 肿瘤坏死因子 基质金属蛋白酶 严重度 细胞凋亡 

摘      要：Background: Biological therapies are a new breakthrough in the treatment of psoriasis and psoriatic arthritis (PsA). Among these, tumour necrosis factor (TNF)- α antagonists such as infliximab and etanercept are the most promising as TNF is considered to be essential in driving cytokine cascade at sites of cutaneous and synovial inflammation in this disease. Objectives: To evaluate the time- related response of serum cytokine release during infliximab monotherapy and assess serum cytokine levels in order to provide a fast, minimally invasive tool to monitor and/or predict efficacy of anti- TNF- α therapy. Methods: Twenty patients affected by PsA with Psoriasis Area and Severity Index (PASI) score between 0.4 and 42.8 were treated with infliximab for 30- 42 weeks. The assessment of arthritis severity was performed using the American College of Rheumatology (ACR) criteria and ultrasonography evaluation. The treatment schedule consisted of infliximab (5 mg kg- 1 intravenously) at 0, 2 and 6 weeks and every 12 weeks on an individual basis determined by therapeutic results and adverse events reported. At baseline and before every infusion blood samples were taken to assess serum cytokine levels [TNF- α , interleukin (IL- 6), E- selectin, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF), matrix metalloproteinase(MMP- 2)]. Results: Eighteen of 20 psoriatic patients achieved50% improvement and 14 of 20 patients attained75% improvement in the PASI score at 10 weeks. All arthritic patients achieved50% improvement (ACR- 50) and 16 of 20 patients attained75% improvement (ACR- 75) at 10 weeks. TNF- α did not decrease immediately during the first part of the study. A significant decrease was detected at week 12 (P 0.01). In contrast, IL- 6, VEGF, FGF and E- selectin showed significant decreases after early infliximab infusions. PASI was not correlated with TNF- α in the serum but was significantly correlated with FGF, VEGF and MMP- 2. Treatment was well tolerated and there were no significant adverse events in most patients, other than an urticarial reaction and an autoimmune hepatitis. Conclusions: Monotherapy with infliximab has to be considered an efficacious and safe treatment for PsA in comparison with traditional disease- modifying antirheumatic drugs. The resolution of cutaneous and synovial symptoms is not related to TNF- α serum levels in the initial phases. Apoptosis may play an important role in the modulation of the inflammatory response.