白芍总苷联合小剂量沙利度胺治疗原发性干燥综合征的安全性和疗效

The safety and efficacy of total glucosides of paeony and low dose of thalidomide for treatment of primary Sjögren's syndrome

目的 :前瞻性比较原发性干燥综合征(p SS)患者接受常规白芍总苷(TGP)单药治疗与TGP联合小剂量沙利度胺(TM)治疗6个月的安全性和疗效。方法:2012年8月至2014年5月我院接受治疗的p SS患者随机分为TGP单药治疗组(TGP组)45例和联合治疗组(TGP/TM组)76例,治疗6个月,对患者的药物相关不良反应(ADR)进行评价,并比较疗效,包括干燥综合征疾病活动指数(SSDAI)、免疫球蛋白G(Ig G)和唾液流率。结果:TGP组出现5例次ADR,仅为轻度腹泻。TGP/TM组观察到67例次ADR,常见有便秘(15.8%,12/76)、颜面或下肢浮肿(13.2%,10/76)、头晕(13.2%,10/76)、手足麻木(10.5%,8/76)和手抖(10.5%,8/76)。16例(21.1%)患者因ADR停用TM。上述ADR均于停药后缓解。治疗6个月后,60例TGP/TM组患者治疗前后SSDAI评分为(5.49±0.62)分和(4.90±0.37)分(t=2.360,P=0.032),44例TGP组患者治疗前后SSDAI评分为(5.71±0.50)分和(5.08±0.44)分(t=2.117,P=0.029),治疗后2组比较差异无统计学意义(t=1.293,P>0.05)。34例TGP/TM组血清Ig G升高患者治疗前后Ig G为(21.56±3.62)g/L和(19.58±2.97)g/L(t=2.703,P=0.016),21例TGP组血清Ig G升高患者治疗前后Ig G为(20.77±3.03)g/L和(20.08±4.16)g/L(t=1.425,P>0.05),治疗后2组比较差异有显著性(t=2.481,P=0.012)。然而,2组治疗前后唾液流率比较差异均无统计学意义(P>0.05)。结论:TGP联合小剂量TM治疗较单用TGP治疗p SS能更有效改善患者血清Ig G。联合治疗ADR发生率虽较高,但多为轻度,可耐受,密切监测下多数患者可安全用药。

Objective To investigate prospectively the safety and efficacy of conventional total glucosides of paeony（TGP） monotherapy and TGP combined with low-dose thalidomide（TGP/TM） for patients with primary Sjgren＇s syndrome（p SS）. Methods Study was conducted on 76 p SS patients who received TGP/TM for 6 months as the treatment group and45 p SS patients who received conventional TGP monotherapy for 6 months as the control group.Adverse drug reaction（ADR） and efficacy criteria including Sjgren＇s syndrome disease activity index（SSDAI）, immunoglobulin G（Ig G） and salivary flow were evaluated. Results Mild diarrhea occurred in 5 cases in TGP group, meanwhile ADR was observed in67 cases in TGP/TM group including constipation（15.8%, 12/76）, facial or leg edema（13.2%, 10/76）, dizziness（13.2%,10/76）, numbness（10.5%, 8/76） and tremor（10.5%, 8/76）. Drugs were withdrawn in 16 cases（21.1%, 16/76） because of ADR, and ADR were remitted as the drugs were stopped. SSDAI of the 60 cases in TGP/TM group before and after 6months of treatment were（5.49 ±0.62） and（4.90±0.37）（t=2.360, P=0.032）, respectively, while that of the 44 cases in the TGP group were（5.71±0.50） and（5.08±0.44）（t=2.117, P=0.029）, respectively. The difference between the two groups was not statistically significant（t=1.293, P0.05）. The serum Ig G of the 34 cases in TGP/TM group before and after treatment were（21.56±3.62） g/L and（19.58±2.97） g/L（t=2.703, P=0.016）, respectively, and that of the 21 cases in TGP group were（20.77 ±3.03） g/L and（20.08 ±4.16） g/L（t =1.425, P〉0.05）, respectively. The difference between the two groups was statistically significant（t =2.481, P =0.012）. However,there was no significant difference in saliva flow between the two groups when compared before and after treatment（P〉0.05）. Conclusions The patients who received TGP combined with low-dose TM could improve more effectively for serum Ig G than those who received TGP monotherapy. The incidence of ADR was higher in patients treated with TGP combined with low-dose TM, however, most of the ADR were mild and well tolerated under close monitoring.