| Background The axial spondyloarthropathy(SpA) is a group of chronic inflammatory rheumatic disease with similar clinical manifestations, pathological and physiological characteristics and genetic characteristics.It is mainly characterized by sacroiliac joint and spinal involvement, but some patients also may appear peripheral joints(hip, knee, shoulder, and ankle) and organ(heart, lung, and kidney) and nervous system involvement. The prevalence of SpA in China has been reported to range from 0.2% to 0.54%.There are more male patients than female patients. This disease is more often seen in people aging 10 to 30 years old with a certain genetic predisposition,and will attack due to disorder of immune system and inflammation system affected certain environmental factors. SpA can be divided into axial type and peripheral type according to the clinical manifestations. Axial SpA(ax-SpA) mainly involves sacroiliac joint and spine, including ankylosing spondylitis(AS), non-radiological axial spinal arthritis, etc. SpA is a heterogeneous disease, namely the disease activity varies largely.With the gradual progression of the disease, some patients will appear joint erosion and osteophyte formation, and some patients are even disabled or lose the labor ability, which seriously influence their quality of life. In addition to improving the clinical symptoms, another treatment needs to be found for delaying the joint destruction and for new bone formation. The ossification mechanisms of SpA may be associated with the imbalance of inflammation, bone destruction, and bone formation in the attachment points and synovium. Wnt protein is vital in the process of bone reconstruction. Dickopff associated protein 1(DKK-1) is a natural suppressor in Wnt signaling pathways. Research shows that the ossification process of AS is associated with Wnt pathway, and DKK-1 expression in AS patients is unbalanced. Recent studies have shown that Wnt/?-catenin pathway is associated with prostaglandin pathway, namely prostaglandin E2(PGE2) can down-regulate negative regulator DKK-1 and sclerostin in Wnt signaling pathway thus up-regulate Wnt pathway and promote osteogenesis process. It is promoted that prostaglandin inhibitors(NSAIDs) may be able to block new bone formation. Studies have reported that a selective COX-2 inhibitor celecoxib(celebrex) can delay the radiographic progress of spine, but the specific mechanism is still unknown. Imrecoxib is a drug with similar mechanism as celecoxib. Whether this kind of drug can improve the condition by influencing serum DKK-1 and then ax-SpA ossification mechanism and finally delaying osteophyte formation? The influences of NSAIDs on ax-SpA ossification mechanism and serum DKK-1 are observed to provide new theoretical basis for ax-SpA treatment, which is of great significance. Objective 1. To observe changes of clinical parameters, inflammatory markers, and radiographic scores and adverse reactions in ax-SpA patients treated by selective COX-2 inhibitor imrecoxib and celecoxib at 4th week and 12 th week. 2. To detect the differences of serum DKK-1 expression in ax-SpA patients before and after selective COX-2 inhibitor treatment; 3. To analyze the correlations between serum DKK-1 expression and clinical parameters, inflammatory markers, and radiographic indicators in ax-SpA patients. Methods 1. 60 cases of ax-SpA patients admitted in department of rheumatism and immunology were enrolled in this study. Their diagnosis was in accordance with the ax-SpA classification standard recommended by ASAS in 2009 and relevant inclusion and exclusion criteria; the included patients were randomly given 200 mg of selective COX-2 inhibitor imrecoxib or celecoxib twice daily; and the patients were recorded for clinical parameters(BASDAI, BASFI, patients global assessment, tragus-to-wall distance, lumbar side flexion, schober test, finger to floor distance, intermalleoar distance), inflammatory markers(ESR, CRP) and adverse reaction at baseline, 4th week and 12 th week; SPARCC method was used to rate MRI results of sacroiliac joint at baseline and 12 th week. 2. Enzyme-linked immunosorbent assay was used to detect serum DKK-1 expression of ax-SpA patients at baseline and 12 th week. Results 1. A total of 60 ax-SpA patients were included in this study and 51 patients(imrecoxib group: n=25, celecoxib group: n=26) eventually completed 12 week of follow-up, who were given clinical efficacy and safety analysis. Compared to baseline, both imrecoxib group and celecoxib group were improved in clinical parameters(BASDAI, BASFI, patients global assessment, tragus-to-wall distance, lumbar side flexion, Schober test, finger to floor distance and intermalleoar distance), inflammatory markers(ESR) at 4th week, and there were no statistically significant differences(P>0.05); CRP of celecoxib group was decreased while that of imrecoxib group was increased at 4th week compared to baseline, and there were no statistically significant differences(P>0.05). Compared to baseline, both imrecoxib group and celecoxib group were improved in clinical indicators and inflammation indicators at 12 th week, and there were no statistically significant differences(P>0.05); and there were no statistically significant differences between two groups of patients in adverse reactions at 12 th week(P>0.05). 2. SPARCC scores of imrecoxib group and celecoxib group were decreased compared to baseline at 12 th week, and there were no statistically significant differences(P>0.05); there were no statistically significant differences between the two groups in serum DKK-1 at 12 th week compared to baseline(P>0.05); 3. There were no correlations between serum DKK-1 and clinical parameters, inflammatory markers, and radiographic scores in imrecoxib group at baseline; and serum DKK-1 of celecoxib group was correlated with BASFI scores(r=-0.048, P=0.027) and Schober test(r=0.437, P=0.048), but not relevant with other parameters. Conclusions 1. Selective COX-2 inhibitors can obviously reduce the symptoms of ax-Sp A and improve body function. Imrecoxib and celecoxib have equivalent efficacy; 2. Selective COX-2 inhibitors imrecoxib and celecoxib have no effects on serum level of DKK-1. |
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