The efficacy and safety of sodium hyaluronate injection (Adant®) in treating degenerative osteoarthritis: A multi-center, randomized, double-blind, positive-drug parallel-controlled and non-inferiority clinical study
Xin Y.,Peking University |
Jianhao L.,Peking University |
Tiansheng S.,Chinese PLA General Hospital |
Yongqiang H.,Shanghai JiaoTong University |
And 7 more authors.
International Journal of Rheumatic Diseases | Year: 2016
Objective: To compare the efficacy and safety of two different sodium hyaluronate drugs in treating degenerative osteoarthritis (OA) of the knee. Method: This randomized, multi-center, double-blind, positive-drug, parallel-controlled study included 229 patients aged ≥ 45 years who were clinically diagnosed with degenerative OA of the knee. The patients were randomly assigned to receive for 5 consecutive weeks a once-weekly intra-articular injection of the investigational drug Adant®, which is manufactured by fermentation, or the control drug Artz®, which is manufactured by extraction of cockscomb. The follow-up examinations were conducted 1, 2, 3, 4 and 6 weeks after the first injection. The primary efficacy parameter was the decrease in the visual analog scale (VAS) scores of pain on movement caused by load-bearing, and the secondary efficacy parameter was the decrease in the Lequesne index. Results: The intra-articular injections of Adant® and Artz® produced a significant reduction in the VAS scores for pain on movement (50.4 and 50.3 mm, respectively) and in the Lequesne index. There were no significant differences in efficacy and safety between the two drugs and non-inferiority in VAS score decreases was confirmed. Conclusion: The results of this study show that both Adant® and Artz® are effective for the treatment of OA and that there were no statistical differences between them in the VAS scores of pain on movement, Lequesne index or safety during the observation period with short-time follow up. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
Feng X.,Nanjing Medical University |
Zou Y.,Wuxi Peoples Hospital |
Pan W.,Huaian No 1 Hospital |
Wang X.,Xuzhou No 4 Peoples Hospital |
And 12 more authors.
Journal of Rheumatology | Year: 2011
Objective. To investigate the mortality of hospitalized patients with systemic lupus erythematosus (SLE) and determine the influential factors associated with poor prognosis. Methods. Medical records of 1956 SLE inpatients from 15 hospitals during the period January 1, 1999, to December 31, 2009, were reviewed. All patients were followed up in January 2010. Potential factors associated with mortality were analyzed, comparing patients who were living with those who were deceased. The independency of those factors significantly related to death was determined by Cox regression analysis. Results. Male to female ratio was 1:15 in this cohort; median age at disease onset was 30 years. Hematologic (70.0%), mucocutaneous (68.2%), musculoskeletal (57.9%), and renal (48.7%) involvements were most often seen in these patients at time of admission. The overall mortality was 8.5% (n = 166), with infection (25.9%), renal failure (19.3%), and neuropsychiatric lupus (18.7%) the leading 3 causes of death. Independent predictors for mortality in this cohort of SLE patients were neuropsychiatric involvement [hazard ratio (HR) 2.19], anemia (HR 1.69), SLEDAI score > 8 at discharge (HR 1.64), increased serum creatinine (HR 1.57), low serum albumin (HR 1.56), cardiopulmonary involvement (HR 1.55), and patient untreated before admission (HR 1.48), whereas the use of antimalarial drugs (HR 0.62) and positive anti-Sm antibody (HR 0.60) were shown to be protective factors. Conclusion. SLE patients with delayed treatment and refractory disease have poorer prognosis. A high incidence of death would be expected if they have neuropsychiatric involvement, anemia, azotemia, or cardiopulmonary involvement. Combination therapy with antimalarial drugs may provide some benefit to patients with SLE.
Zhang W.,Capital Medical University |
Zhang J.,Chinese Academy of Sciences |
Hoadley K.,University of North Carolina at Chapel Hill |
Kushwaha D.,Dana-Farber Cancer Institute |
And 10 more authors.
Neuro-Oncology | Year: 2012
Genome-wide microRNA (miRNA) profiling of 82 glioblastomas demonstrated that miR-181d was inversely associated with patient overall survival after correcting for age, Karnofsky performance status, extent of resection, and temozolomide (TMZ) treatment. This association was validated using the Cancer Genome Atlas (TCGA) dataset (n 424) and an independent cohort (n 35). In these independent cohorts, an association of miR-181d with survival was evident in patients who underwent TMZ treatment but was not observed in patients without TMZ therapy. Bioinformatic analysis of potential genes regulated by miR-181d revealed methyl-guanine-methyl-transferase (MGMT) as a downstream target. Indeed, transfection of miR-181d downregulated MGMT mRNA and protein expression. Furthermore, luciferase reporter assays and coprecipitation studies showed a direct interaction between miR-181d and MGMT 3UTR. The suppressive effect of miR-181d on MGMT expression was rescued by the introduction of an MGMT cDNA. Finally, MGMT expression inversely correlated with miR-181d expression in independent glioblastoma cohorts. Together, these results suggest that miR-181d is a predictive biomarker for TMZ response and that its role is mediated, in part, by posttranscriptional regulation of MGMT. © 2012 The Author(s).
Wang D.,Nanjing Medical University |
Li J.,Jiangsu University |
Zhang Y.,Peoples Hospital of Jiangsu Province |
Zhang M.,Jiangsu Provincial Peoples Hospital |
And 4 more authors.
Arthritis Research and Therapy | Year: 2014
Introduction: In our present single-center pilot study, umbilical cord (UC)-derived mesenchymal stem cells (MSCs) had a good safety profile and therapeutic effect in severe and refractory systemic lupus erythematosus (SLE). The present multicenter clinical trial was undertaken to assess the safety and efficacy of allogeneic UC MSC transplantation (MSCT) in patients with active and refractory SLE.Methods: Forty patients with active SLE were recruited from four clinical centers in China. Allogeneic UC MSCs were infused intravenously on days 0 and 7. The primary endpoints were safety profiles. The secondary endpoints included major clinical response (MCR), partial clinical response (PCR) and relapse. Clinical indices, including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, British Isles Lupus Assessment Group (BILAG) score and renal functional indices, were also taken into account.Results: The overall survival rate was 92.5% (37 of 40 patients). UC-MSCT was well tolerated, and no transplantation-related adverse events were observed. Thirteen and eleven patients achieved MCR (13 of 40, 32.5%) and PCR (11 of 40, 27.5%), respectively, during 12 months of follow up. Three and four patients experienced disease relapse at 9 months (12.5%) and 12 months (16.7%) of follow-up, respectively, after a prior clinical response. SLEDAI scores significantly decreased at 3, 6, 9 and 12 months follow-up. Total BILAG scores markedly decreased at 3 months and continued to decrease at subsequent follow-up visits. BILAG scores for renal, hematopoietic and cutaneous systems significantly improved. Among those patients with lupus nephritis, 24-hour proteinuria declined after transplantation, with statistically differences at 9 and 12 months. Serum creatinine and urea nitrogen decreased to the lowest level at 6 months, but these values slightly increased at 9 and 12 months in seven relapse cases. In addition, serum levels of albumin and complement 3 increased after MSCT, peaked at 6 months and then slightly declined by the 9- and 12-month follow-up examinations. Serum antinuclear antibody and anti-double-stranded DNA antibody decreased after MSCT, with statistically significant differences at 3-month follow-up examinations.Conclusion: UC-MSCT results in satisfactory clinical response in SLE patients. However, in our present study, several patients experienced disease relapse after 6 months, indicating the necessity to repeat MSCT after 6 months.Trial registry: ClinicalTrials.gov identifier: NCT01741857. Registered 26 September 2012. © 2014 Wang et al.; licensee BioMed Central Ltd.
Feng X.,Nanjing Medical University |
Zou Y.,Wuxi Peoples Hospital |
Pan W.,Huaian No1 Hospital |
Wang X.,Xuzhou No4 Peoples Hospital |
And 12 more authors.
Lupus | Year: 2014
The objective of this study is to evaluate the association of clinical features and prognosis with age at disease onset in patients with systemic lupus erythematosus (SLE) in a large, multicenter Chinese cohort. Medical records of 1898 SLE inpatients from 15 hospitals were reviewed and classified into three groups according to their ages at disease presentation. Categorical data were analyzed by chi-square test and potentially associated factors were tested by multinomial logistic regression. Among the patients studied, 259 (13.6%) were juvenile onset (≤18 years), 1444 (76.1%) were early onset (>18 and ≤45 years) and 195 (10.3%) were late onset (>45 years). Whenever manifestations occurred, most patients (>80%) were diagnosed within two years. Juvenile-onset patients were more likely to be untreated before admission (p < 0.001) and have mucocutaneous manifestations (p < 0.001), but musculoskeletal symptoms (p < 0.05) and leukopenia (p < 0.05) were less frequent, while comorbidities were much higher in patients with late-onset SLE (p < 0.001). Neuropsychiatric, cardiopulmonary, renal and gastrointestinal involvement, disease activity index and damage scores were similar among three groups. Anti-Sm antibodies were less prevalent in late-onset patients (p < 0.05) and antimalarial drugs were more often applied to juvenile-onset patients (p < 0.001). As expected, mortality was elevated in the late-onset SLE group (p < 0.05), in which nearly half died of infections, which was much higher than those in the other two groups (p < 0.001). Logistic regression confirmed that patients with juvenile- and early-onset disease were associated with high incidence of being untreated prior to admission, and with low incidence of comorbidities as well as deaths caused by infection compared to patients with late-onset lupus. Interestingly, our data showed that more patients with late-onset disease had a SLEDAI score change of >7 at discharge. In conclusion, age at onset has an impact on SLE disease status, and infection is the main cause of death in those with late-onset lupus. Considering that the late-onset patients had simultaneously easily controllable diseases and high incidence of comorbidities, a different treatment strategy from younger patients should be considered. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
The efficacy and safety of sodium hyaluronate injection (Adant®) in treating degenerative osteoarthritis: a multi-center, randomized, double-blind, positive-drug parallel-controlled and non-inferiority clinical study
PubMed | Chinese PLA General Hospital, Shanghai JiaoTong University, Peking University and Jiangsu Provincial Peoples Hospital
Type: Journal Article | Journal: International journal of rheumatic diseases | Year: 2016
To compare the efficacy and safety of two different sodium hyaluronate drugs in treating degenerative osteoarthritis (OA) of the knee.This randomized, multi-center, double-blind, positive-drug, parallel-controlled study included 229 patients aged 45 years who were clinically diagnosed with degenerative OA of the knee. The patients were randomly assigned to receive for 5 consecutive weeks a once-weekly intra-articular injection of the investigational drug Adant, which is manufactured by fermentation, or the control drug Artz, which is manufactured by extraction of cockscomb. The follow-up examinations were conducted 1, 2, 3, 4 and 6 weeks after the first injection. The primary efficacy parameter was the decrease in the visual analog scale (VAS) scores of pain on movement caused by load-bearing, and the secondary efficacy parameter was the decrease in the Lequesne index.The intra-articular injections of Adant and Artz produced a significant reduction in the VAS scores for pain on movement (50.4 and 50.3 mm, respectively) and in the Lequesne index. There were no significant differences in efficacy and safety between the two drugs and non-inferiority in VAS score decreases was confirmed.The results of this study show that both Adant and Artz are effective for the treatment of OA and that there were no statistical differences between them in the VAS scores of pain on movement, Lequesne index or safety during the observation period with short-time follow up.
Li M.,Peking Union Medical College |
Zhang W.,Peking Union Medical College |
Leng X.,Peking Union Medical College |
Li Z.,Bengbu Medical College |
And 11 more authors.
Lupus | Year: 2013
The Chinese systemic lupus erythematosus (SLE) treatment and research group (CSTAR) provides major clinical characteristics of SLE in China and establishes a platform to provide resources for future basic and clinical studies. CSTAR originated as a multicentre, consecutive, and prospective design. The data were collected online from 104 rheumatology centers, which covered 30 provinces in China. The registered patients were required to meet four or more of the American College of Rheumatology (ACR) criteria for the classification of SLE. All CSTAR centers use the same protocol-directed methods to provide uniform evaluations, which included demographic data, clinical features, laboratory examinations, and disease activity evaluations. The patient samples, including DNA samples and sera, were also collected for further quality controls and additional studies. Preliminary analysis from 2104 baseline evaluations was available for this analysis. Of 1914 female and 190 male patients (F:M = 10.1), the mean age at onset was 29.2 y with confirmed diagnosis one year later at the age of 30.3 y. Eighty four (4.2%) of 2002 patients had a family history of rheumatic diseases, including 34 (1.7%) cases with SLE. In addition, one hundred and seven (5.2%) abnormal pregnancies were recorded among 2026 experiences. The characteristics of the CSTAR cohort were compared to similarly sized cohorts from other studies. We found that 56.1% of patients presented with concurrent hematological disorders compared to only 18.2% of European patients. Moreover, 47.4% of patients presented with nephropathy compared to 27.9% of European patients. Conversely, neurological manifestations were only seen in 4.8% of Chinese SLE patients compared to 19.4% of European patients, 12.1% of U.S. patients, 22.8% of Malaysian patients and 26.4% of Latin Americans. Pulmonary arterial hypertension and interstitial lung diseases were complications identified in 3.8% and 4.2% of Chinese lupus patients, respectively. The CSTAR registry has provided epidemiological data and phenotypes of Chinese patients with SLE, and has demonstrated several differences between ethnicities. Clinical data and biologic samples would be valuable resources for future translational studies with national and international collaboration. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Li M.,Peking Union Medical College |
Wang Q.,Peking Union Medical College |
Zhao J.,Peking Union Medical College |
Li Z.,Bengbu Medical College |
And 14 more authors.
Lupus | Year: 2014
Objectives: To estimate the prevalence of pulmonary arterial hypertension (PAH) and risk factors for PAH in patients registered in the Chinese SLE Treatment and Research group (CSTAR) database, the first online registry of Chinese patients with systemic lupus erythematosus (SLE). Methods: A prospective cross-sectional study of patients with SLE was conducted using the CSTAR registry. Resting transthoracic echocardiography was used to estimate pulmonary artery pressure (PAP); PAH was defined as systolic PAP (PASP) ≥40 mmHg. Patients with interstitial lung disease, valvular disease or cardiomyopathy were excluded because of disease influence on PAP. We explored potential risk factors for PAH including patient characteristics, organ involvement, laboratory findings and SLE disease activity. Results: Of 1934 patients with SLE, 74 had PASP with 54.2±17.1 (40,106) mmHg and were diagnosed with probable PAH. The incidences of lupus nephritis, pleuritis, pericarditis, hypocomplementemia, anti-SSA, and anti-ribonucleoprotein (RNP) were significantly higher in patients with PAH than in those without (p<0.05). SLE disease activity was significantly higher in patients with PAH than in unaffected patients (p<0.05). Multivariate analysis indicated that pericarditis (odds ratio (OR)=4.248), pleuritis (OR=3.061) and anti-RNP (OR=2.559) were independent risk factors for PAH in patients with SLE (p<0.05). Conclusions: The possible prevalence of PAH was 3.8% in Chinese patients with SLE in the CSTAR registry. The significant association of pericarditis, pleuritis and anti-RNP positivity with PAH suggests that higher disease activity and vasculopathy may both contribute to the development of PAH in SLE, which need be treated aggressively to improve prognosis. © The Author(s), 2014.
Zhu L.,Fudan University |
Yu J.,Wuxi Hand Surgery Hospital |
Zhang W.,Jiangsu Provincial Peoples Hospital |
Xie B.,Nanjing University |
And 2 more authors.
Molecular Medicine Reports | Year: 2014
The period circadian clock 2 (per2) gene plays an important role in modulating the circadian rhythm in the central nervous system. Its protein product, PER2, is mainly expressed in the suprachiasmatic nucleus (SCN) and limbic system, including the central nucleus of the amygdala (CeA), the bed nucleus of the stria terminalis (BNST) and the hippocampus. PER2 rhythmic expression regulates hypothalamus pituitary adrenal (HPA) axis excitability and circadian rhythm via integration of optical signals and corticotropin releasing factor (CRF) stress related neurotransmitters, resulting in circadian rhythmicity in target organs. Moreover, glucocorticoids and glucocorticoid receptors exert strong negative feedback to the HPA axis and certain regions of the limbic system, modulating rhythmic per2 expression in peripheral organs. To date, the mechanism of action of PER2 in the limbic system and the HPA axis remains unclear, yet the per2 gene is considered valuable in clinical research for the study of metabolic syndromes, functional gastrointestinal disorders and certain liver diseases. In this review, we summarize the biological effects of the per2 gene and its protein product, PER2, in the limbic system, its involvement in regulation of the HPA axis by the limbic system and the resulting effects on the biological rhythm of target organs, and its clinical significance.