Division of Rheumatology, Department of Medicine, University of Ulsan, College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
Clin Rheumatol. 2018 Dec;37(12):3215-3220. doi: 10.1007/s10067-018-4005-6. Epub 2018 Jan 30.
The objective of this study was to investigate risk factors for cytopenia when a prophylactic dose of trimethoprim-sulfamethoxazole (TMP-SMX) was co-administered with methotrexate (MTX). Patients who received MTX with or without a prophylactic dose of TMP-SMX were included. Patients who received a therapeutic dose of TMP-SMX were excluded. The MTX-alone and MTX with TMP-SMX groups (MTX group and MTX + TMP-SMX group, respectively) were matched in a 4:1 ratio according to age, creatinine level, mean corpuscular volume and MTX dose. Cytopenia was defined as a haemoglobin level decrease by > 2 g/dl, platelet count of < 150,000/mm or white blood cell count of < 3500/mm. The Cox proportional hazards model was used to evaluate risk factors for cytopenia in patients administered with MTX. The incidence of cytopenia did not significantly differ between the MTX group and MTX + TMP-SMX group (5.0 vs 5.7%, p > 0.999). According to the Cox proportional hazards model, chronic liver disease (hazard ratio [HR] 5.829, 95% confidence interval [CI] 1.211-28.063, p = 0.028) was associated with an increased risk of cytopenia. However, the concomitant use of a prophylactic dose of TMP-SMX (HR 1.717, 95% CI 0.352-8.371, p = 0.504) was not significantly associated with an increased risk of cytopenia. Compared with the use of MTX alone, the concomitant use of MTX with a prophylactic dose of TMP-SMX was not significantly associated with an increased risk of cytopenia. Thus, a prophylactic dose of TMP-SMX can be safely used with MTX.
本研究旨在探讨甲氨蝶呤（MTX）预防性使用复方磺胺甲噁唑（TMP-SMX）时发生细胞减少症的危险因素。纳入接受 MTX 治疗或 MTX 联合预防性 TMP-SMX 治疗的患者。排除接受治疗剂量 TMP-SMX 的患者。将 MTX 单药治疗组（MTX 组）和 MTX 联合 TMP-SMX 组（MTX+TMP-SMX 组）按照年龄、肌酐水平、平均红细胞体积和 MTX 剂量以 4:1 的比例进行匹配。细胞减少症定义为血红蛋白水平下降>2g/dl、血小板计数<150,000/mm3 或白细胞计数<3500/mm3。采用 Cox 比例风险模型评估 MTX 治疗患者发生细胞减少症的危险因素。MTX 组和 MTX+TMP-SMX 组的细胞减少症发生率无显著差异（5.0%比 5.7%，p>0.999）。根据 Cox 比例风险模型，慢性肝病（危险比 [HR]5.829，95%置信区间 [CI]1.211-28.063，p=0.028）与细胞减少症风险增加相关。然而，预防性使用 TMP-SMX（HR 1.717，95%CI 0.352-8.371，p=0.504）与细胞减少症风险增加无显著相关性。与 MTX 单药治疗相比，MTX 联合预防性 TMP-SMX 治疗与细胞减少症风险增加无显著相关性。因此，MTX 可安全联合预防性 TMP-SMX 使用。
