Smolen J S, Han C, Bala M, Maini R N, Kalden J R, van der Heijde D, Breedveld F C, Furst D E, Lipsky P E
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna and Lainz Hospital, Vienna, Austria.
Arthritis Rheum. 2005 Apr;52(4):1020-30. doi: 10.1002/art.20982.
To assess the relationship between inflammation and joint destruction in rheumatoid arthritis (RA) patients who have not responded clinically to treatment.
Changes from baseline to week 54 in clinical variables and measures of radiographic progression were compared between patients who received infliximab (3 mg/kg or 10 mg/kg every 4 or 8 weeks) plus methotrexate (MTX) and those who received MTX plus placebo in the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy trial.
At week 54, patients who did not show 20% improvement by American College of Rheumatology criteria (ACR20 nonresponders) while receiving infliximab plus MTX exhibited mild but statistically significant improvement in clinical variables, including the 28-joint Disease Activity Score (DAS28) (P < 0.001), tender joint count (P = 0.014), swollen joint count (P < 0.001), and C-reactive protein (CRP) level (P < 0.001). Whereas the clinical and CRP changes among ACR20 nonresponders to infliximab plus MTX were small and much lower than among ACR20 responders to this treatment, radiographic progression among ACR20 nonresponders to infliximab plus MTX was significantly inhibited (P < 0.001) compared with ACR20 nonresponders to MTX plus placebo. Radiographic progression was much greater in patients receiving MTX plus placebo than in patients receiving infliximab plus MTX, irrespective of ACR response status (mean change in modified Sharp/van der Heijde score 6.0 in ACR20 responders and 7.2 in ACR20 nonresponders in the MTX plus placebo-treated group, versus 0.1 in ACR20 responders and 1.2 in ACR20 nonresponders in the infliximab plus MTX-treated group). Furthermore, among patients who were ACR20 nonresponders through week 54, patients who were DAS nonresponders at weeks 30 and 54, and patients without any improvement in individual clinical variables, those receiving infliximab plus MTX still demonstrated inhibition of structural damage that was statistically significant compared with inhibition in patients who received MTX plus placebo (P < 0.05 to P < 0.001).
Even in patients without clinical improvement, treatment with infliximab plus MTX provided significant benefit with regard to the destructive process, suggesting that in such patients these 2 measures of disease are dissociated.
评估在临床上对治疗无反应的类风湿关节炎（RA）患者中炎症与关节破坏之间的关系。
在类风湿关节炎联合治疗试验的抗肿瘤坏死因子试验中，比较接受英夫利昔单抗（每4或8周3mg/kg或10mg/kg）加甲氨蝶呤（MTX）的患者与接受MTX加安慰剂的患者从基线到第54周临床变量和放射学进展指标的变化。
在第54周时，接受英夫利昔单抗加MTX治疗但未达到美国风湿病学会标准（ACR20无反应者）改善20%的患者，其临床变量有轻度但具有统计学意义的改善，包括28个关节疾病活动评分（DAS28）（P<0.001）、压痛关节计数（P=0.014）、肿胀关节计数（P<0.001）和C反应蛋白（CRP）水平（P<0.001）。虽然英夫利昔单抗加MTX治疗的ACR20无反应者的临床和CRP变化较小且远低于该治疗的ACR20反应者，但与MTX加安慰剂治疗的ACR20无反应者相比，英夫利昔单抗加MTX治疗的ACR20无反应者的放射学进展受到显著抑制（P<0.001）。无论ACR反应状态如何，接受MTX加安慰剂治疗的患者的放射学进展比接受英夫利昔单抗加MTX治疗的患者大得多（MTX加安慰剂治疗组中ACR20反应者改良Sharp/van der Heijde评分的平均变化为6.0，ACR20无反应者为7.2，而英夫利昔单抗加MTX治疗组中ACR20反应者为0.1，ACR20无反应者为1.2）。此外，在第54周时为ACR20无反应者、在第30周和第54周时为DAS无反应者以及个体临床变量无任何改善的患者中，接受英夫利昔单抗加MTX治疗的患者与接受MTX加安慰剂治疗的患者相比，其结构损伤的抑制仍具有统计学意义（P<0.05至P<0.001）。
即使在无临床改善的患者中，英夫利昔单抗加MTX治疗在破坏过程方面也提供了显著益处，这表明在这类患者中这两种疾病指标是分离的。
