Tumor Necrosis Factor-Alpha (+489 G/A) Polymorphism Can Predict the Response to Adalimumab in Chinese Han Patients With Ankylosing Spondylitis.

BACKGROUND: Studies investigating the association between single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and the efficacy of adalimumab (ADA) in ankylosing spondylitis (AS) therapy have reported conflicting results. We aimed to investigate the value of SNP typing of TNFα in predicting the efficacy of ADA in AS. MATERIALS AND METHODS: Eighty patients with active AS who received ADA treatment were followed up for 24 weeks. Six known SNPs of TNFα (+489G/A, -238G/A, -308G/A, -857C/T, -863C/A, and -1031C/T) were subjected to the SNaPshot SNP typing method, which has been proven to be a reliable, efficient, and cost-effective method for detecting SNPs. The relationship between each SNP genotype and the therapeutic efficacy of ADA was analyzed. RESULTS: At the end of the 24-week follow-up, 58.8% of the patients with AS achieved Assessment of SpondyloArthritis International Society (ASAS) partial remission (PR), 67.5% of the patients achieved the criteria of an ASAS40 response (40% improvement on indices), and 53.8% of the patients achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement (MI). The univariate analysis showed that patients with AS carrying the TNFα +489 A allele were more likely to achieve ASAS-PR, ASAS40 response criteria, and ASDAS-MI after ADA treatment. In the multivariate regression analysis, the TNFα +489 A allele was an independent factor influencing the efficacy of ADA in treating AS (ASAS-PR odds ratio (OR) = 2.66, 95% confidence interval (CI) = 1.01-7.01; ASAS40 OR = 4.56, 95% CI = 1.39-15.00; ASDAS-MI OR = 3.31, 95% CI = 1.02-10.69). CONCLUSIONS: The patients carrying the TNFα +489 A allele may be more likely to experience better therapeutic efficacy and achieve the treatment target (ASAS-PR, ASAS40 response, or ASDAS-MI) after receiving ADA treatment. Detection of TNFα +489 G/A may predict the therapeutic efficacy of ADA, which can be used in clinical practice to tailor treatment for individual patients with AS. Further studies with larger sample sizes and longer follow-up periods with imaging evaluation are needed to verify our findings.

Comparison of clinical characteristics between adult-onset and juvenile-onset non-radiographic axial spondyloarthritis in Chinese patients: results from the COCAS cohort.

BACKGROUND: Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease predominantly affecting the axial skeleton. We aimed to describe the clinical characteristics of patients with non-radiographic axSpA (nr-axSpA) in China and compare the differences between adult- and juvenile-onset cases. METHODS: A cross-sectional study was conducted using data from 776 patients with nr-axSpA in the Clinical Characteristic and Outcome in Chinese Axial Spondyloarthritis (COCAS) study cohort. Patients were divided into two groups including the adult-onset group (n = 662) and the juvenile-onset group (n = 114) according to age at disease onset. Baseline demographics and clinical characteristics were compared between patients with adult-onset and juvenile-onset nr-axSpA. RESULTS: Overall, the male-to-female ratio was 1.26:1, the prevalence of HLA-B27 positivity was 72.2%, and the median age at disease onset of nr-axSpA was 22 years. Nearly 75% of nr-axSpA patients had peripheral arthritis in the disease course, and the prevalence of extra-articular manifestations was 10.4%. The juvenile-onset group contained a higher proportion of men (66.7% vs. 53.9%, P = 0.011) and a longer baseline disease duration (4.0 [4.0] vs. 1.6 [3.5], P < 0.001) than the adult-onset group. A family history of spondyloarthritis was more frequent in the juvenile-onset group than in the adult-onset group (23.7% vs. 15.4%, P = 0.028), but no significant difference in the prevalence of HLA-B27 positivity was observed between the two groups (P = 0.537). Regarding initial symptoms, peripheral arthritis occurred more often in patients with juvenile-onset nr-axSpA, whereas patients with adult-onset nr-axSpA presented more frequently with axial involvement. The prevalence of inflammatory back pain (IBP) was higher in the adult-onset group than in the juvenile-onset group (85.0% vs. 75.4%, P = 0.010), whereas the juvenile-onset group showed a higher prevalence of peripheral arthritis and enthesitis than the adult-onset group (67.5% vs. 48.5%, P < 0.001; 35.1% vs. 23.3%, P = 0.007, respectively). CONCLUSIONS: Compared with adult-onset nr-axSpA, juvenile-onset nr-axSpA was more common in men and those with a family history of spondyloarthritis. Juvenile-onset nr-axSpA presents with a "peripheral predominant" mode at disease onset and a higher frequency of peripheral arthritis and enthesitis during the disease course.

Risk factors for progression of juvenile-onset non-radiographic axial spondyloarthritis to juvenile-onset ankylosing spondylitis: a nested case-control study.

OBJECTIVE: To evaluate the clinical characteristics of juvenile-onset non-radiographic axial spondyloarthritis (nr-axSpA) and to investigate risk factors associated with progression to juvenile-onset ankylosing spondylitis (JoAS). METHODS: A nested case-control study was conducted using the retrospectively collected data of 106 patients with juvenile-onset nr-axSpA (age at disease onset, <16 years) in the Clinical characteristic and Outcome in Chinese Axial Spondyloarthritis study cohort. Baseline demographic and clinical characteristics and prognosis were reviewed. Logistic regression analyses were performed to investigate risk factors associated with progression to JoAS. RESULTS: Overall, 58.5% of patients with juvenile-onset nr-axSpA presented with peripheral symptoms at disease onset. In 82.1% of these patients, axial with peripheral involvement occurred during the disease course. The rate of disease onset at >12 years and disease duration of ≤10 years were significantly higher in those with progression to JoAS than in those without progression to JoAS (83.0% vs 52.8%, p=0.001; 92.5% vs 56.6%, p<0.001, respectively). Multivariable logistic regression analysis revealed that inflammatory back pain (IBP) (OR 13.359 (95% CI 2.549 to 70.013)), buttock pain (OR 10.171 (95% CI 2.197 to 47.085)), enthesitis (OR 7.113 (95% CI 1.670 to 30.305)), elevated baseline C reactive protein (CRP) levels (OR 7.295 (95% CI 1.984 to 26.820)) and sacroiliac joint-MRI (SIJ-MRI) positivity (OR 53.821 (95% CI 9.705 to 298.475)) were significantly associated with progression to JoAS. CONCLUSION: Peripheral involvement was prevalent in juvenile-onset nr-axSpA. IBP, buttock pain, enthesitis, elevated baseline CRP levels and SIJ-MRI positivity in patients with the disease are associated with higher risk of progression to JoAS.

Pannus inflammation in sacroiliitis following immune pathological injury and radiological structural damage: a study of 193 patients with spondyloarthritis.

BACKGROUND: The pathogenesis of sacroiliitis is unclear; therefore, we aimed to systematically study the immunopathology of sacroiliitis in patients with axial spondyloarthritis (axSpA), and explore the relationship between pannus formation, inflammation, and the structural damage caused by sacroiliitis. METHODS: Fine needle aspiration biopsy of the sacroiliac joint (SIJ) was performed in 193 patients with axSpA. Clinical, laboratory, and imaging data were collected at baseline and during the follow up. Immunohistochemistry analysis was performed to detect CD34+ microvessels, CD68+ osteoclasts/macrophages, vascular endothelial growth factor (VEGF), metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), and caspase-3. Autopsy subjects were used as controls. RESULTS: In early sacroiliitis (grade 0-1) all pathological features could be observed, with the most common being subchondral pannus formation. Among the 193 patients, 98 were followed up for 1-13 years (mean 3.6 years); 63.3% had radiological progression at the endpoint. Multiple regression analysis showed that cartilage pannus invasion (OR 2.99, P = 0.010) and endochondral ossification (OR 3.97, P = 0.049) at baseline were risk factors for radiological structural damage. Compared to SIJ controls, the subchondral microvessel density, number of CD68+ multinuclear osteoclasts, and the levels of VEGF, caspase-3, MMP-3, and TNF-α expressed at the interface of the bone and cartilage were significantly higher in patients with sacroiliitis. CONCLUSIONS: Subchondral fibrovascular tissue formation is the most important pathological feature in early sacroiliitis. The existence of cartilage pannus invasion or endochondral ossification at baseline can predict radiological structural damage during the follow up.

Changes in the Prevalence of Rheumatic Diseases in Shantou, China, in the Past Three Decades: A COPCORD Study.

This study aimed to clarify changes in the prevalence of rheumatic diseases in Shantou, China, in the past 3 decades and validate whether stair-climbing is a risk factor for knee pain and knee osteoarthritis (KOA). The World Health Organization-International League Against Rheumatism Community Oriented Program for Control of Rheumatic Diseases (COPCORD) protocol was implemented. In all, 2337 adults living in buildings without elevators and 1719 adults living in buildings with elevators were surveyed. The prevalence of rheumatic pain at any site and in the knee was 15.7% and 10.2%, respectively; both types of pain had a significantly higher incidence in residents of buildings without elevators than was reported by people who lived in buildings with elevators (14.9% vs. 10.6% and 11.32% vs. 8.82%, respectively) (both P < 0.0001). The prevalence of rheumatic pain in the neck, lumbar spine, shoulder, elbow, and foot was 5.6%, 4.5%, 3.1%, 1.4%, and 1.8%, respectively; these findings were similar to the data from the 1987 rural survey, but were somewhat lower than data reported in the urban and suburban surveys of the 1990s, with the exception of neck and lumbar pain. The prevalence of KOA, gout, and fibromyalgia was 7.10%, 1.08%, and 0.07%, respectively, and their prevalence increased significantly compared with those in previous studies from the 20th century. There were no significant differences in the prevalence of rheumatoid arthritis (RA) (0.35%) or ankylosing spondylitis (AS) (0.31%) compared to that reported in prior surveys. The prevalence of KOA was higher in for residents of buildings without elevators than that in those who had access to elevators (16-64 years, 5.89% vs. 3.95%, P = 0.004; 16->85 years, 7.64% vs. 6.26%, P = 0.162). The prevalence of RA and AS remained stable, whereas that of KOA, gout, and fibromyalgia has increased significantly in Shantou, China, during the past 3 decades. Stair-climbing might be an important risk factor for knee pain and KOA.

Prevalence and risk factors of osteoporosis in patients with ankylosing spondylitis: a 5-year follow-up study of 504 cases.

OBJECTIVES: The objective of this study was to assess the prevalence and risk factors of osteoporosis (OP) in patients with ankylosing spondylitis (AS). METHODS: Demographic and clinical data of 504 AS patients were collected. Bone mineral density (BMD) measurements of the lumbar spine, proximal femur and forearm were performed by dual-energy x-ray absorptiometry at baseline and follow-up. 106 cases of sex- and age-matched healthy volunteers were enrolled as normal controls. RESULTS: In contrast to normal controls, AS patients displayed a higher prevalence of both OP (9.7% vs. 0%) and osteopenia (57.5% vs. 34.9%). The prevalence of OP was significantly higher and the BMD were significantly lower in patients with elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) than patients with normal ESR and CRP. Juvenile onset, morning stiffness lasting over 0.5 hours and elevated ESR levels were risk factors for bone loss at the lumbar spine; Male gender, older age, hip involvement and lack of regular treatment were risk factors for bone loss at the femur. 173 cases were followed up for 1 to 5 years, BMD changes per year at the lumbar spine, femur and forearm were 4.8%, 2.7%, and 2.6% respectively. There was no significant difference in annual BMD change between patients treated with or without low dose glucocorticoids (GCs). Hip involvement and persistent elevated ESR levels, but not GCs treatment, were associated with decreased BMD at both the lumbar spine and the femur during follow-up in longitudinal regression analysis. CONCLUSIONS: High disease activity and hip involvement are risk factors of bone loss in patients with AS. Low-dose GCs treatment in AS does not increase the risk of OP.