Kremer Joel, Ritchlin Christopher, Mendelsohn Alan, Baker Daniel, Kim Lilianne, Xu Zhenhua, Han John, Taylor Peter
Albany Medical College and The Center for Rheumatology, Albany, New York 12206, USA.
Arthritis Rheum. 2010 Apr;62(4):917-28. doi: 10.1002/art.27348.
To assess the efficacy and safety of intravenous administration of golimumab in patients with rheumatoid arthritis (RA).
Adult patients with RA in whom disease activity was persistent despite treatment with methotrexate (MTX) at a dosage of 15-25 mg/week for > or = 4 weeks were randomized to receive intravenous infusions of placebo plus MTX or intravenous infusions of golimumab at a dose of 2 mg/kg or 4 mg/kg, with or without MTX, every 12 weeks through week 48. Patients with <20% improvement in the swollen and tender joint counts could enter early escape and receive additional active treatment (week 16) or could have their dose regimen adjusted (week 24). The primary end point was the proportion of patients achieving a 50% response according to the American College of Rheumatology improvement criteria (ACR50) at week 14.
The primary study end point was not met (at week 14, an ACR50 response was observed in 21% of the patients treated with golimumab plus MTX compared with 13% of the patients treated with placebo plus MTX [P = 0.051]). By week 24, significantly more patients treated with golimumab plus MTX had achieved an ACR50 response. Differences in the proportion of patients achieving an ACR50 response between the group receiving golimumab monotherapy and the group receiving placebo plus MTX were not significant at either week 14 (16% versus 13%) or week 24 (10% versus 9%). At week 48, the proportions of patients achieving ACR20 and ACR50 responses were highest among those who had received golimumab 4 mg/kg plus MTX (70% and 48%, respectively). Concomitant treatment with MTX was associated with a lower incidence of antibodies to golimumab. The most commonly reported adverse events through week 48 were infections (48% of patients treated with golimumab with or without MTX and 41% of patients receiving placebo plus MTX).
The primary end point was not met. However, intravenously administered golimumab plus MTX appears to have benefit in the longer-term reduction of RA signs/symptoms in MTX-resistant patients, with no unexpected safety concerns.
评估静脉注射戈利木单抗治疗类风湿关节炎（RA）患者的疗效和安全性。
成年RA患者，尽管以15 - 25毫克/周的剂量服用甲氨蝶呤（MTX）≥4周，但疾病活动仍持续存在，将其随机分组，每12周接受一次静脉输注安慰剂加MTX，或静脉输注2毫克/千克或4毫克/千克的戈利木单抗，可联合或不联合MTX，持续至第48周。肿胀和压痛关节计数改善<20%的患者可提前退出并接受额外的积极治疗（第16周），或调整剂量方案（第24周）。主要终点是根据美国风湿病学会改善标准（ACR50）在第14周时达到50%缓解的患者比例。
未达到主要研究终点（在第14周时，接受戈利木单抗加MTX治疗的患者中有21%观察到ACR50缓解，而接受安慰剂加MTX治疗的患者中这一比例为13%[P = 0.051]）。到第24周时，接受戈利木单抗加MTX治疗的患者中达到ACR50缓解的比例显著更高。在第14周（16%对13%）或第24周（10%对9%），接受戈利木单抗单药治疗组与接受安慰剂加MTX治疗组之间达到ACR50缓解的患者比例差异均无统计学意义。在第48周时，接受4毫克/千克戈利木单抗加MTX治疗的患者中达到ACR20和ACR50缓解的比例最高（分别为70%和48%）。联合MTX治疗与抗戈利木单抗抗体的发生率较低相关。到第48周时最常报告的不良事件是感染（接受戈利木单抗治疗的患者中有48%，无论是否联合MTX，接受安慰剂加MTX治疗的患者中有41%）。
未达到主要终点。然而，静脉注射戈利木单抗加MTX似乎对MTX抵抗患者的RA体征/症状有长期缓解作用，且无意外的安全问题。
