| Background:Ankylosing spondylitis is a chronic, inflammation and advanced disease characterized,which is the typical type of spondyloarthopathy. The spine and sacroiliac joint are the most common involved joints. Some patients may involve in peripheral joints and extra-articular manifestations, such as hip, knee, ankle, shoulder and heart, lungs, kidneys involvement. Meanwhile, AS is distinguished by universal involvement with sacroiliac joint inflammation or fusion and more prevalent new bone formation and spinal ankylosng, like bamboo spine and hip involvement,which seriously affect the normal activities and the quality of life.Non-steroidal anti-inflammatory drugs(NSAIDs) which is conserved as the first-line pharmaceutical therapy in patients with AS,not only can relieve the signs and symptoms, but also exhibit a disease-modifying effect. It was already reported that celecoxib can delay spinal radiographic progression in AS. However,Imrecoxib made in china is lack of research in AS. Does Imrecoxib have the same effect as well as celecoxib in AS?The new bone formation is the primary reason resoulting in disability and it is very important for clinical work to seek the reason resulted in new bone formation.Bone morphogenetic proteins(BMP) is the most important molecular which can guide to the bone formation, promot osteoblast differentiation and induce blood vessels, muscle, mesenchymal cells and fibroblasts into irreversible bone cells. Meanwhile, vascular endothelial growth factor(VEGF) is a signal protein that plays a crucial role in angiogenesis and endochondral ossification, which may participate in the new bone formation in AS.The inflammatory in AS is closely related to overexpression of COX-2, NSAIDs can reduce inflammation by inhibiting cyclooxygenase and then reducing the synthesis of prostaglandin. Cyclooxygenase can influence angiogenesis, tumor development and bone metastases by influencing the expression of VEGF and BMP-2. Moreover, celecoxib, a selective COX-2 inhibitor, can relieve spinal radiographic progression in patients with AS.However,the mechanism is not unkown. Is the radiographic progression association with the serum levels VEGF and BMP-2? Can selective COX-2 inhibitor have the influence on the levels of VEGF and BMP-2? Currently there were no reports about the efficacy on the levels of VEGF and BMP-2 by trestment with selective COX-2 inhibitor in AS.In this study,we aimed to evaluate the efficacy of the selective COX-2 inhibitor in AS and to investigate the impact on the radiographic score and levels of VEGF and BMP-2. Objective:1 To evaluate the efficacy of the COX-2 selective inhibitor in patients with AS And compare the efficacy between imrecoxib and celecoxib..2 To assess the influence on radiographic score in AS treatment with selective COX-2 inhibitor.3 To observe the influence on serum levels of VEGF and BMP-2 in AS treatment with selective COX-2 inhibitor, and the relationship between VEGF,BMP-2 and radiographic score. Methods:120 patients with AS were admitted to this study.They were all outpatients at the First Affiliated Hospital of Zhengzhou University, Division of Rheumatology from October 2014 to October 2015.They were required to meet relevant inclusion and exclusion criteria. and then randomized into the two groups, imrecoxib or celecoxib,respectively.And patients were recorded for basic clinical characteristics(age, gender, disease duration) before treatment. The clinical parameters which include laboratory parameters(ESR, CRP), disease activity(BASDAI score), functional evaluation(BASFI, patients global assessment,tragus-up-wall distance, lumbar side flexion, intermalleoar distance,Schober test, finger to floor distance) were detected at baseline and at 4th week and 12 th week, The sacroiliac joint SPARCC score and the levels of serum VEGF,BMP-2 were detected at baseline and at 12 th week. Results:1 There were 120 patients were recruited. Among them, 116 patients completed the follow-up, included 57 patients in imrecoxib group and 59 patients in celecoxib group. There was no significant difference between two groups in gender and age. A statistically significant change was found in ESR, BASDAI,patients global assessment of disease activity,intermalleoar distance,Schober test and finger to floor distance after 4 and 12 weeks by treatment with the selective COX-2 inhibitor,(P <0.05); However,there was no statistically significant change in CRP level at 12 weeks,and in BASFI, tragus-up-wall distance and lumbar side flexion(P > 0.05) at 4 weeks and 12 weeks. The changes of CRP were statistically significant difference(P < 0.05) at 4 weeks when compared between the two groups, the other parameters were no statistically significance between the two groups.(P > 0.05). The ANOVA for repeated measures showed that the time effects was statistically significant(P <0.05) in ESR, CRP, BASDAI, patients global assessment,intermalleoar distance,finger to floor distance in three time points. However, the treatment effects and time effects were statistically significant in CRP(P < 0.05).2 There were statistically significant change in sacroiliac joint SPARCC at 12 weeks by treatment with the selective COX-2 inhibitor,(P <0.05);There were no statistically significant difference in sacroiliac joint SPARCC between the two groups.The correlation analysis showed SPARCC were positively correlated with ESR, Schober test, lumbar side flexion(P <0.05), and negative with age, duration disease, tragus-up-wall distance(P <0.05); and there were no correlation between SPARCC and CRP, BASDAI, BASFI, patients global assessment of disease activity(P > 0.05).3 There were statistically significant changes in the levels of VEGF at 12 weeks by treatment with the selective COX-2 inhibitor(P <0.05),not in BMP-2. The Spearman Correlation analysis showed that a significant correlation between serum VEGF and BMP-2(P <0.05).In addition, VEGF positively correlated with BMP-2,PLT,ESR,CRP, BASFI,tragus-up-wall and finger to floor distance, and negatively with HGB, lumbar side flexion,Schober,intermalleoar distance(P <0.05). Moreover the BMP-2 positively correlated with ESR, and negatively with lumbar side flexion(P <0.05). Conclusions:1 Selective COX-2 inhibitor can relieve the diease activity of AS and reduce marrow edema of sacroiliac joint. In additional, imrecoxib and celecoxib have a same efficacy.2 Selective COX-2 inhibitors can reduce the levels of VEGF. The levels of serum VEGF marked the disease activity of AS,but not the radiographic inflammation. Whereas, whether BMP-2 reflects radiographic progression requires further investigation. |
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