Voulgari Paraskevi V, Alamanos Yannis, Nikas Spyros N, Bougias Dimitrios V, Temekonidis Themistoklis I, Drosos Alexandros A
Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece.
Am J Med. 2005 May;118(5):515-20. doi: 10.1016/j.amjmed.2005.01.029.
To investigate the efficacy, toxicity and drug discontinuation rate in an observational study of patients with established rheumatoid arthritis treated with infliximab.
Between September 1999 and June 2003, we enrolled 84 patients with rheumatoid arthritis who were being treated with infliximab. All patients met the American College of Rheumatology criteria for rheumatoid arthritis and had been refractory to (or did not tolerate) at least two disease-modifying antirheumatic drugs. Patients entering the study had a negative purified protein derivative skin test, were fully informed about the treatment regimen, and were followed up at predefined times according to a standardized protocol. Data concerning infliximab dosage, tolerability, adverse events, concomitant therapy, dosage interval, and drug discontinuation were all recorded. In addition, the clinical and laboratory variables according to the American College of Rheumatology 20% and 50% response criteria and the disease activity score for the 28 joint indices were also recorded.
There were 61 women and 23 men with a mean age of 59 +/- 8 years and mean disease duration of 11 +/- 6 years. Seventy-five percent (63/84) were seropositive for IgM rheumatoid factor. After the first year of treatment, 84.5% of patients continued to be treated with infliximab, whereas this percentage was 73% after the second year and 59% after the third year of treatment. The American College of Rheumatology 20% response criteria was met by 59/84 (70%) of patients, and 38/84 (45%) of the patients achieved the 50% response criteria in the first year of treatment. At the second year of therapy, the American College of Rheumatology 20% response criteria were reached by 35/84 (42%) of the patients and the 50% response criteria by 27/84 (32%). At the third year of treatment with infliximab, the American College of Rheumatology 20% and 50% response criteria were achieved by 13/84 (15.5%) and 10/84 (12%) of the patients, respectively. Twenty-eight of eighty-four (33%) patients discontinued infliximab therapy. The risk of drug discontinuation decreased with the concomitant use of methotrexate. The main reasons for drug discontinuation were adverse drug reactions (16/84, 19%), followed by lack of efficacy (9/84, 11%). The main reasons for drug discontinuation due to side effects were immediate hypersensitivity reactions (9/84, 11%) and infections (6/84, 7%).
Infliximab was found to be an alternative treatment with a relatively acceptable toxicity profile, despite the fact that two patients developed pulmonary tuberculosis. After the third year of therapy, 59% of patients continued to be treated with infliximab. The concomitant use of methotrexate was associated with the continuation of infliximab therapy.
在一项关于英夫利昔单抗治疗已确诊类风湿关节炎患者的观察性研究中，调查其疗效、毒性及药物停用率。
1999年9月至2003年6月期间，我们纳入了84例正在接受英夫利昔单抗治疗的类风湿关节炎患者。所有患者均符合美国风湿病学会类风湿关节炎标准，且对至少两种改善病情抗风湿药物难治（或不耐受）。进入研究的患者结核菌素纯蛋白衍生物皮肤试验呈阴性，充分了解治疗方案，并按照标准化方案在预定时间进行随访。记录有关英夫利昔单抗剂量、耐受性、不良事件、联合治疗、给药间隔及药物停用的数据。此外，还记录了根据美国风湿病学会20%和50%反应标准以及28个关节指数的疾病活动评分的临床和实验室变量。
有61名女性和23名男性，平均年龄59±8岁，平均病程11±6年。75%（63/84）的患者IgM类风湿因子呈阳性。治疗第一年结束后，84.5%的患者继续接受英夫利昔单抗治疗，而在治疗第二年和第三年后，这一比例分别为73%和59%。84例患者中有59例（70%）在治疗第一年达到美国风湿病学会20%反应标准，38例（45%）达到50%反应标准。在治疗第二年，84例患者中有35例（42%）达到美国风湿病学会20%反应标准，27例（32%）达到50%反应标准。在英夫利昔单抗治疗第三年，84例患者中分别有13例（15.5%）和10例（12%）达到美国风湿病学会20%和50%反应标准。84例患者中有28例（33%）停止英夫利昔单抗治疗。联合使用甲氨蝶呤可降低药物停用风险。药物停用的主要原因是药物不良反应（16/84，19%），其次是疗效不佳（9/84，11%）。因副作用导致药物停用的主要原因是即刻超敏反应（9/84，11%）和感染（6/84，7%）。
尽管有两名患者发生了肺结核，但发现英夫利昔单抗是一种毒性相对可接受的替代治疗方法。治疗第三年后，59%的患者继续接受英夫利昔单抗治疗。甲氨蝶呤的联合使用与英夫利昔单抗治疗的持续有关。
