St Clair E William, van der Heijde Désirée M F M, Smolen Josef S, Maini Ravinder N, Bathon Joan M, Emery Paul, Keystone Edward, Schiff Michael, Kalden Joachim R, Wang Ben, Dewoody Kimberly, Weiss Roberta, Baker Daniel
Duke University Medical Center, Durham, North Carolina, USA.
Arthritis Rheum. 2004 Nov;50(11):3432-43. doi: 10.1002/art.20568.
To compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti-tumor necrosis factor alpha [anti-TNFalpha] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of < or =3 years' duration.
RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFalpha inhibitor. One thousand forty-nine patients were randomly assigned in a 4:5:5 ratio to 3 treatment groups: MTX-placebo, MTX-3 mg/kg infliximab, and MTX-6 mg/kg infliximab. MTX dosages were rapidly escalated to 20 mg/week, and infliximab or placebo infusions were given at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46.
At week 54, the median percentage of American College of Rheumatology improvement (ACR-N) was higher for the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than for the MTX-placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001 for both comparisons). Patients in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone (mean +/- SD changes in van der Heijde modification of the total Sharp score at week 54: 0.4 +/- 5.8 and 0.5 +/- 5.6 versus 3.7 +/- 9.6, respectively; P < 0.001 for each comparison). In addition, physical function improved significantly more in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than in the MTX-placebo group. Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia.
For patients with active RA in its early stages, combination therapy with MTX and infliximab provides greater clinical, radiographic, and functional benefits than treatment with MTX alone.
比较甲氨蝶呤（MTX）联合英夫利昔单抗（抗肿瘤坏死因子α[抗TNFα]单克隆抗体）起始治疗与单用MTX治疗对病程≤3年的类风湿关节炎（RA）患者的疗效。
若RA患者疾病活动且未接受过MTX或TNFα抑制剂治疗，则符合入组条件。1049例患者按4:5:5的比例随机分为3个治疗组：MTX-安慰剂组、MTX-3mg/kg英夫利昔单抗组和MTX-6mg/kg英夫利昔单抗组。MTX剂量迅速增至20mg/周，英夫利昔单抗或安慰剂分别在第0、2和6周输注，此后每8周输注1次，直至第46周。
在第54周时，MTX-3mg/kg英夫利昔单抗组和MTX-6mg/kg英夫利昔单抗组美国风湿病学会改善率（ACR-N）的中位数高于MTX-安慰剂组（分别为38.9%和46.7%，而MTX-安慰剂组为26.4%；两组比较P均<0.001）。MTX-3mg/kg英夫利昔单抗组和MTX-6mg/kg英夫利昔单抗组患者的影像学进展也少于单用MTX治疗的患者（第54周时van der Heijde改良总Sharp评分的平均±标准差变化：分别为0.4±5.8、0.5±5.6和3.7±9.6；每次比较P<0.001）。此外，MTX-3mg/kg英夫利昔单抗组和MTX-6mg/kg英夫利昔单抗组患者的身体功能改善明显优于MTX-安慰剂组。英夫利昔单抗治疗与严重感染尤其是肺炎的发生率显著升高相关。
对于早期活动性RA患者，MTX与英夫利昔单抗联合治疗比单用MTX治疗能带来更大的临床、影像学和功能改善。
