Klippel J H
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892.
J Rheumatol. 1990 Sep;17(9):1118-22.
Major advances in the therapy of RA will likely require future scientific breakthroughs in the understanding of pathophysiology. That is not to suggest that clinical investigations should be put on hold while the entire focus of research shifts to the laboratory bench. Clinical studies of very early RA, including early treatment interventions, would appear to be of major importance. However, better characterization of the early clinical course and identification of pathologic markers of progressive disease are needed before formal randomized treatment studies of early disease can be initiated. The entire role of aggressive management, particularly with combination chemotherapy, at any stage of RA is in desperate need of answers. In clinical practice it would appear that combination chemotherapy is widely used, often as a last resort in treatment resistant patients who have failed conventional therapies. The published clinical studies would seem to support, but certainly not prove, a valuable potential role for combination chemotherapy in this setting. Moreover, the studies seem to indicate some increased risk of drug toxicities, the limitations of which are not readily apparent for most combinations. Based on the successes observed in these patients that are very difficult to treat, the possibility of a more fundamental role of combination chemotherapy in treatment of the disease has been advocated. These questions need to be resolved by well designed, randomized controlled trials. There is an urgent need to do the trials soon before combination chemotherapy gains an even stronger foothold in therapy.
类风湿关节炎（RA）治疗方面的重大进展可能需要未来在病理生理学理解上取得科学突破。这并非意味着在研究重点完全转向实验室研究时，临床研究就应搁置。对极早期RA的临床研究，包括早期治疗干预，似乎至关重要。然而，在启动早期疾病的正式随机治疗研究之前，需要更好地描述早期临床病程并确定疾病进展的病理标志物。在RA的任何阶段，积极治疗，特别是联合化疗的整体作用迫切需要答案。在临床实践中，联合化疗似乎被广泛使用，通常作为对常规治疗无效的难治性患者的最后手段。已发表的临床研究似乎支持，但肯定不能证明，联合化疗在这种情况下具有潜在的重要作用。此外，研究似乎表明药物毒性风险有所增加，而对于大多数联合用药方案，其局限性并不明显。基于在这些难治性患者中观察到的成功案例，有人主张联合化疗在该疾病治疗中可能发挥更根本的作用。这些问题需要通过精心设计的随机对照试验来解决。迫切需要尽快开展这些试验，以免联合化疗在治疗中占据更稳固的地位。
