Westhovens R, Robles M, Ximenes A C, Nayiager S, Wollenhaupt J, Durez P, Gomez-Reino J, Grassi W, Haraoui B, Shergy W, Park S-H, Genant H, Peterfy C, Becker J-C, Covucci A, Helfrick R, Bathon J
UZ Gasthuisberg, Department of Rheumatology, B-3000 Leuven, Belgium.
Ann Rheum Dis. 2009 Dec;68(12):1870-7. doi: 10.1136/ard.2008.101121. Epub 2009 Jan 5.
To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors.
In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (approximately 10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout.
At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone.
In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.
评估阿巴西普在未使用过甲氨蝶呤且具有不良预后因素的早期类风湿关节炎(RA)患者中的疗效和安全性。
在这项双盲IIIb期研究中,病程2年及以内的RA患者按1:1随机分组,分别接受阿巴西普(约10mg/kg)联合甲氨蝶呤或安慰剂联合甲氨蝶呤治疗。患者未使用过甲氨蝶呤,类风湿因子(RF)、抗环瓜氨酸肽2(CCP)抗体或两者均为血清学阳性,且有影像学关节侵蚀证据。共同主要终点为第1年达到28个关节疾病活动评分(DAS28)定义的缓解(C反应蛋白)的患者比例和关节损伤进展(Genant改良Sharp总分;TS)。全程监测安全性。
基线时,患者的平均DAS28为6.3,平均TS为7.1,平均病程为6.5个月;96.5%和89.0%的患者分别为RF或抗CCP2血清学阳性。第1年时,与单用甲氨蝶呤相比,接受阿巴西普联合甲氨蝶呤治疗的患者达到缓解的比例显著更高(41.4%对23.3%;p<0.001),影像学进展显著更少(TS的平均变化为0.63对1.06;p = 0.040)。在1年期间,阿巴西普联合甲氨蝶呤与单用甲氨蝶呤相比,不良事件发生率(84.8%对83.4%)、严重不良事件发生率(7.8%对7.9%)、严重感染发生率(2.0%对2.0%)、自身免疫性疾病发生率(2.3%对2.0%)和恶性肿瘤发生率(0.4%对0%)相当。
在未使用过甲氨蝶呤、患有早期RA且具有不良预后因素的人群中,与单用甲氨蝶呤相比,阿巴西普联合甲氨蝶呤具有显著更好的临床和影像学疗效,且安全性相当且良好。