Csuka M, Carrera G F, McCarty D J
JAMA. 1986 May 2;255(17):2315-9.
Cyclophosphamide, azathioprine, and hydroxychloroquine sulfate were prescribed for 31 patients (26 women and five men) with rheumatoid arthritis refractory to conventional therapy. Maintenance drug dosages (mean +/- SD) were as follows: cyclophosphamide, 30 +/- 24 mg/day; azathioprine, 74 +/- 44 mg/day; and hydroxychloroquine sulfate, 210 +/- 92 mg/day. Disease suppression began in 30 patients within three to 24 months (mean, nine months). Results after 43 months (range, 12 to 102 months) were as follows: 16, complete remission; seven, near remission; seven, partial disease suppression; one, no response. None remained in prolonged remission without some form of therapy. Treatment was discontinued in three patients because of pulmonary infection (two) or thrombocytopenia (one). Four patients had five malignant neoplasms (surgical cures) before therapy (two breast, one colon, one melanoma, one endometrial); four patients developed a malignant neoplasm during combined drug therapy (one colon, one endometrial, one lung, one erythroleukemia); and three died. The absolute risk of malignancy from combined drug therapy is still unclear. We concluded that combined use of remittive agents may have promise in treatment of severe rheumatoid arthritis; cyclophosphamide should be replaced with a nonalkylating agent; and the place of combined drug therapy remains uncertain in the absence of controlled trials.
环磷酰胺、硫唑嘌呤和硫酸羟氯喹被用于治疗31例（26名女性和5名男性）对传统疗法难治的类风湿性关节炎患者。维持药物剂量（均值±标准差）如下：环磷酰胺，30±24毫克/天；硫唑嘌呤，74±44毫克/天；硫酸羟氯喹，210±92毫克/天。30例患者在3至24个月（平均9个月）内病情开始得到控制。43个月（范围12至102个月）后的结果如下：16例完全缓解；7例接近缓解；7例部分病情得到控制；1例无反应。没有患者在未接受某种形式治疗的情况下长期缓解。3例患者因肺部感染（2例）或血小板减少症（1例）而停止治疗。4例患者在治疗前有5例恶性肿瘤（手术治愈）（2例乳腺癌、1例结肠癌、1例黑色素瘤、1例子宫内膜癌）；4例患者在联合药物治疗期间发生恶性肿瘤（1例结肠癌、1例子宫内膜癌、1例肺癌、1例红白血病）；3例死亡。联合药物治疗导致恶性肿瘤的绝对风险仍不清楚。我们得出结论，联合使用缓解药物可能对严重类风湿性关节炎的治疗有前景；环磷酰胺应用非烷化剂替代；在缺乏对照试验的情况下，联合药物治疗的地位仍不确定。
