抗肿瘤坏死因子α单克隆抗体治疗强直性脊柱炎的短期临床观察

A short-term efficacy and safety study of infliximab in active ankylosing spondylitis

目的评价负荷剂量的抗肿瘤坏死因子α单克隆抗体infliximab治疗强直性脊柱炎（AS）的临床疗效和安全性。方法本研究为2个中心的开放性Ⅱ期临床试验，患者为确诊的AS患者，并且疾病处于活动期。患者分别在试验的第0、2、6周接受静脉输注infliximab5mg／kg，并随访至10周，主要疗效指标为达到AS疗效评价标准20（ASAS20）的患者比例，次要疗效指标包括达到临床显效的患者比例，与基线值相比BathAS疾病活动指数（BASDAI）、BathAS功能指数、BathAS测量指数、脊柱痛、夜间痛、脊柱炎症、病人总体评估指数、肌腱端炎指数、整体关节肿胀指数、生活质量健康问卷SF-36改善的状况。结果63例患者（男性占79％，平均年龄32岁，平均病程10年，HLA-B27阳性占90％）纳入研究，第10周试验结束时，84％的患者达到ASAS20的改善程度；有30％的患者达到临床显效标准；70％的患者达到BASDAI评分改善大于50％，54％的患者达到BASDAI评分改善大于70％。其他各项疗效指标也反映出相似的改善程度及趋势。最常见的不良反应为上呼吸道感染和皮肤及其附属器官的损害，其次是肝功能异常，2例患者发生严重的皮炎伴有脱发，1例患者在第3次输注药物过程中因出现输注反应而停药。近期随访结果显示，疗效可持续2～8个月，停止治疗后无新的不良反应发生。结论负荷剂量infliximab的安全性和耐受性好，能迅速减轻AS的症状和体征，并可改善AS患者的功能、活动范围和生活质量。

Objective To evaluate the efficacy and safety profile of a loading regimen of the anti- TNFα antibody infliximab in ankylosing spondylitis （AS）. Methods This was an open-labeled trial. Subjects eligible for this study were adults with a diagnosis of definite AS. Active disease was a Bath AS disease activity index （BASDAI） ≥4 and spinal pain VAS ≥4. Concurrent stable treatment with nonsteroidal anti-inflammatory drugs was permitted during the study. Subjects were not permitted to be on methotrexate, systemic corticosteroids, cytotoxic drugs or disease-modifying anti-rheumatic drugs for various time periods before screening. Infliximab 5 mg/kg was infused at weeks 0, 2, 6. All patients were followed up to 10 weeks. The primary endpoint was proportion of ASAS 20 responders at week 10. The secondary endpoints were the proportion of subjects achieving an ASAS partial remission, the change from baseline in bath AS functional index and in the physical component summary score of the short form-36 in health survey questionnaire at week 10. Other secondary endpoints, related to reducing signs and symptoms of AS and improving range of motion and physical function, were evaluated. Results 63 patients （79% males, 90% HLA-B27^＋, median age 32yr, median disease duration 10yr） completed the treatment. The proportion of ASAS 20 responders at 2,6,10 week was 75%, 84%, 84% respectively. The proportion of ASAS partial remission patients at 2,6,10 week was 10% , 21% , 30% respectively. Results for other secondary efficacy endpoints showed that infliximab could provide substantial benefits to patients with AS by reducing clinical signs and symptoms and improving range of motion, physical function, and quality of life. Sixty-five percent of subjects reported treatment-rclated adverse events. The most frequently occurred were upper respiratory tract infection and skin and appendages. Secondary was elevation of liver enzymes. Most treatment-related adverse events were mild to moderate in severity. Two patients had serious dermatitis and one stopped treatment owing to an infusion reaction. Short-term follow up indicated that effect of Remicade lasted for about 2 to 8 months without any new side effect. Conclusion A loading regimen of infliximab demonstrated consistent evidence of efficacy and was well tolerated in the treatment of active AS.