ObjectiveTo systematically review the effectiveness and safety of thalidomide for ankylosing spondylitis (AS).
MethodsDatabases including Ovid MEDLINE (1946 to 2014.2.1), EMbase (1947 to 2014.2.1), CENTRAL (Issue 1, 2014), CBM (1978 to 2014.2.1), CNKI (1994 to 2014.2.1), WanFang Data (1980 to 2014.2.1) and VIP (1989 to 2014.2.1) were searched for randomized controlled trials about the effectiveness and safety of thalidomide for AS. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Meta-analysis was then conducted using RevMan 5.2 software.
ResultsSeven RCTs were included involving 544 patients. The results of meta-analysis showed that, compared with the blank group, thalidomide increased clinical remission, but it showed no obvious advantage in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and secondary outcome index, with an increased total rate of withdrawal/drop-out. Compared with SSZ, thalidomide increased the rate of maintaining remission when it was used in the maintenance treatment after the patients attained ASAS20; and for other outcomes it was similar to SSZ. Compared with NSAIDs, thalidomide increased the rate of maintaining remission when it was used in the maintenance treatment after the patients attained ASAS20; it increased clinical remission; for secondary outcomes it was similar to NSAIDs; and it had a higher incidence of adverse reaction as well as an increased total rate of withdrawal/drop-out.
ConclusionCompared with the blank group, thalidomide increases clinical remission, with an obviously-increased total rate of withdrawal/drop-out. Compared with SSZ, thalidomide increases the rate of maintaining remission when it is used in the maintenance treatment after patients attain ASAS20. Compared with NSAIDs, thalidomide increases the rate of maintaining remission when it is used in the maintenance treatment after patients attain ASAS20; it also increases clinical remission; but it has a higher incidence of adverse reaction as well as an increased total rate of withdrawal/drop-out. Due to limited quantity and quality of the included studies, the above conclusion needs to be verified by conducting more high quality studies.
【摘要】 目的 研究沙利度胺對人慢性粒細胞白血病急變株K562細胞凋亡及血管內皮生長因子（vascular endothelia growth factor，VEGF）分泌的影響。 方法 采用不同濃度的沙立度胺（0.5、1.0、2.0 mmol/L）作用于K562細胞24、48、72、96 h，瑞-姬（Wright-Giemsa）染色法觀察細胞形態；四甲基偶氮唑鹽（methylthiazolyl tetrozolium，MTT）法檢測細胞增殖；流式細胞儀膜聯蛋白V-異硫氰酸熒光素/碘化丙啶雙染法檢測凋亡率；瓊脂糖凝膠電泳法檢測脫氧核糖核酸梯狀條帶；酶聯免疫吸附法檢測VEGF濃度。 結果 培養24、48 h后，沙立度胺對K562細胞生長無抑制作用；作用72 h后，1.0、 2.0 mmol/L濃度組開始出現對K562細胞生長的抑制（Plt;0.001）；作用96 h后，0.5 mmol/L濃度組也產生對K562細胞生長的抑制（Plt;0.001），呈一定的濃度和時間依賴性。沙立度胺處理72 h后，K562細胞出現形態學改變，其體積縮小，出現空泡化，邊緣出現突起，染色質濃縮、邊集，核固縮、出現凋亡小體。經沙立度胺處理后，流式分析結果顯示K562細胞凋亡率增加（Plt;0.001）。沙立度胺作用72 h后，瓊脂糖凝膠電泳可見典型的DNA梯狀條帶。K562細胞培養48 h后，沙立度胺抑制VEGF的分泌（Plt;0.001），并且VEGF濃度與凋亡率呈負相關（r=-0.789）。 結論 沙利度胺抑制K562細胞的增殖，呈一定的濃度和時間依賴性；沙利度胺對K562細胞凋亡有明顯誘導作用；沙利度胺抑制K562細胞VEGF的分泌。【Abstract】 Objective To investigate the effect of thalidomide on apoptosis of k562 cells and its vascular endothelial growth factor secretion. Methods K562 cells were cultured in vitro with 0.5, 1.0, and 2.0 mmol/L thalidomide for 24, 48, 72, and 96 hours. Morphology of the K562 cells was observed by the Wright-Giemsa staining method. Methylthiazolyl tetrozolium （MTT） assay was used to determine the cell growth. The rate of apoptosis was analyzed by flow cytometry (FCM) with annexin V-fluorescein isothiocyanate/propidium iodide （AnnexinV-FITC/PI）double-staining method. Agarose gel electrophoresis was used to detected Deoxyribonucleic acid Ladder（DNA Ladder）. The concentration of VEGF was quantified by the enzyme-linked immunosorbent assay (ELISA). Results Cultured for 24 or 48 hours, thalidomide had no effect on the proliferation of the K562 cells. But after cultured for 72 hours, thalidomide began to inhibit the growth of the K562 cells at the concentration of 1.0 and 2.0 mmol/L （Plt;0.001）. After cultured for 96 hours, the proliferation of the K562 cells was inhibited too at the concentration of 0.5 mmol/L thalidomide （Plt;0.001）. Thus, thalidomide inhibited the growth of the K562 cells with a dose-and time-dependent manner to some extent. After exposure to thalidomide for 72 hours, K562 cells underwent typical morphological changes of apoptosis such as vaculization, the budding of cytoplasm, chromatin condensation, margination, shrunken nucleus and apoptotic body. The results of flow cytometry showed that thalidomide could obviously increase the rates of the apoptosis of K562 cells （Plt;0.001）. After treated with thalidomide for 72 hours, DNA was extracted for Agarose gel electrophoresis and typical DNA ladder strips were observed. The secretion of VEGF was inhibited when exposure to thalidomide for 48 hours（Plt;0.001）, and there was negative correlation between VEGF concentrations and apoptotic rates（r=-0.789）. Conclusions Thalidomide could inhibite the growth of the K562 cells with a dose-and time-dependent manner to some extent. Thalidomide could obviously induce the apoptosis of the K562 cells and inhibit its secretion of VEGF.
Objective To assess the effectiveness and safety of thalidomide for treating multiple myeloma in China. Methods Randomized controlled trials (RCTs) of thalidomide for multiple myeloma were collected from CNKI (1979 to 2008), CBMdisc (1979 to 2008), and VIP (1989 to 2008) databases. Other relevant journals were also handsearched. The methodological quality of the included studies was evaluated, and data analyses were performed using the Cochrane Collaboration’s software RevMan 4.3. Results A total of 9 RCTs involving 324 patients were included. As for the total effective rate and complete remission rate, significant differences were found between thalidomide + MP vs. MP alone (RR=1.34, 95%CI 1.05 to 1.70; RR=1.77, 95%CI 1.26 to 2.49) and thalidomide + VAD vs. VAD alone (RR=1.45, 95%CI 1.20 to 1.75; RR=1.73, 95%CI 1.25 to 2.39). Conclusion According to the domestic evidence, treatment for multiple myeloma with thalidomide can improve the total effective rate and the complete remission rate. However, more high–quality, large-sample, randomized, double-blind, controlled trials are required.
ObjectiveTo investigate the efficacy of sulfasalazine combined with thalidomide in the treatment of spondyloarthropathy (SpA), and to probe whether the treatment can reach and maintain clinical remission for the patients.
MethodBetween January 2011 and June 2013, we used a prospective, non-intervention and regular follow-up study to observe and assess 70 SpA patients on their Bath ankylosing spondylitis disease activity index, visual analogue scale score, peripheral arthritis, blood sedimentation, and C-reactive protein. All the patients had taken sulfasalazine, thalidomide and non-steroidal anti-inflammatory drugs for 24 weeks. Multivariate analysis of factors affecting the efficacy of the program was our object of this study.
ResultsAfter 24 weeks, the total clinical remission rate of these patients was 72.9%. Clinical remission rate of 40 patients with short duration of SpA was 90.0%, while it was 50.0% for the other 30 patients with a non-short duration of SpA. Observation indexes before and after treatment in both groups of patients had significant differences (P<0.05). For patients with non-short duration SpA, the curative effect for female was obviously better than male, but the difference between male and female patients with short-duration SpA was not so obvious. Clinical remission rate for youth was similar with that for non-youth patients. Binary logistic regression analysis showed that whether the disease had a short duration[OR=3.408, 95%CI (1.637, 7.437), P=0.001] and whether the patients were urban residents[OR=4.163, 95%CI (2.011, 8.761), P=0.001] were statistically significant (P<0.05).
ConclusionsClinical remission of spondyloarthropathy can be maintain by sulfasalazine combined with thalidomide. Clinical remission rate of the scheme is affected by duration of disease and residency except age and gender of the patients. Short duration and urban residency are independent factors for reaching clinical remission after treatment.
Objective To evaluate the effectiveness of PTD regimen (pamidronate disodium + thalidomide + dexamethasone) and TD regimen (thalidomide + dexamethasone) in the treatment of multiple myeloma. Methods The patients meeting the inclusion criteria were randomly treated with PTD and TD regimens from January 2004 to December 2008. The effectiveness and safety of the two groups were observed after 8 weeks and the statistical analyses were performed using SPSS 13.0 software. Results A total of 25 patients were included, of which 13 were treated with PTD regimen and the other 12 were treated with TD regimen. The results showed overall response rates were 84.6% and 83.3% in the PTD and TD groups, respectively, with no significant difference (Pgt;0.05). The complete response rate (5/13 vs. 1/12) and early response rate (within 2 weeks, 4/13 vs. 1/12) for bone pain in the PTD group were better than those of TD group (Plt;0.05). Conclusion Compared with TD regimen, PTD regimen has more dramatic and faster effects on bone pain relief for multiple myeloma, but for overall response rate, further larger sample size randomized controlled trials are needed.
ObjectiveTo systematically review the effect of thalidomide as first-line therapy on postrelapse survival rate of patients with multiple myeloma (MM).
MethodsDatabases including PubMed, EMbase, The Cochrane Library (Issue 1, 2007) and Web of Science were searched to collect randomized controlled trials (RCTs) about thalidomide as first-line therapy for MM from 2006 to 2011. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.1 software.
ResultsA total of 16 RCTs involving 6097 patients were included. The results of meta-analysis showed that, compared with the chemotherapy alone group, early application of thalidomide could significantly decrease the postrelapse survival rate (HR=1.23, 95%CI 1.05 to 1.45, P=0.002). Subgroup analysis showed that, compared with the chemotherapy alone group, thalidomide maintenance therapy after autologous stem cell transplantation (ASCT) couldn’t decrease the postrelapse survival rate (HR=0.90, 95%CI 0.57 to 1.41, P=0.64), but thalidomide induction therapy before ASCT (HR=1.21, 95%CI 1.01 to 1.45, P=0.04) and thalidomide induction therapy before ASCT combined maintenance therapy after ASCT (HR=1.41, 95%CI 1.13 to1.76, P=0.002) could significantly decrease the postrelapse survival rate.
ConclusionCurrent evidence shows that, thalidomide maintenance therapy after ASCT for MM is a better therapy regimen. It couldn’t decrease the survival rate after recurrence, but could increase the disease-free survival (DFS) and overall survival (OS) of patients with MM. Due to the limited quality of included studies, the above conclusion still needs to be verified by more high quality studies.
