Clinical efficacy of alternative TNF inhibitor and secukinumab between primary non-responder and secondary non-responder of prior TNF inhibitor in ankylosing spondylitis.

OBJECTIVES: To compare the drug retention times and clinical efficacy of alternative tumour necrosis factor inhibitors (TNFi) and secukinumab in primary and secondary non-responders with ankylosing spondylitis (AS). METHODS: AS patients treated with biologics and enrolled in the Korean College of Rheumatology Biologics registry were examined. Patients who did not respond to previous TNFi treatment were defined as primary and secondary non-responders. Data regarding drug discontinuation and clinical efficacy were collected after 1 year. Kaplan-Meier and Cox regression analyses were performed to compare drug survival and associated factors. Logistic regression analyses were conducted to compare the clinical efficacy secukinumab with that of alternative TNFi. RESULTS: In total, 124 patients (83 receiving alternative TNFi and 41 receiving secukinumab) had biologic changes due to clinical inefficacy. Drug retention rates in the alternative TNFi and secukinumab groups were similar (P = 0.096). However, subgroup analyses including only secondary non-responders revealed that secukinumab users showed a higher hazard ratio (HR) for drug discontinuation (HR = 3.77, P = 0.045). In addition, secukinumab was negatively associated with achieving BASDAI50 or a major improvement in the ASDAS. CONCLUSION: Alternative TNFi showed better drug retention and clinical efficacy in AS patients experiencing previous TNFi failure, in secondary non-responders. Therefore, alternative TNFi may be a more suitable treatment for secondary non-responders.

Retention rate and effectiveness of secukinumab vs TNF inhibitor in ankylosing spondylitis patients with prior TNF inhibitor exposure.

OBJECTIVES: The choice of second-line biologics for AS patients previously treated with a TNF inhibitor (TNFi) remains unclear. Here, we compared drug retention and clinical efficacy between AS patients who switched biologics to secukinumab and those who switched to a different TNFi. METHODS: AS patients enrolled in the Korean College of Rheumatology BIOlogics registry were included, and patients with non-radiographic axial spondyloarthritis were excluded. Patients with previous TNFi exposure were divided into the secukinumab group and the TNFi switching group. Drug retention and clinical efficacy [BASDAI50, Assessment of Spondylo-Arthritis International Society (ASAS)20, ASAS40, AS disease activity score (ASDAS) <2.1, ASDAS clinically important improvement and ASDAS major improvement] were assessed at the 1 year follow-up. Propensity score (PS)-matched and covariate-adjusted logistic regression analyses were performed. RESULTS: Two hundred and forty-six had available 1 year follow-up data. Secukinumab as third- or later-line biologic was more frequent than alternative TNFi (54% vs 14%). PS-matched and multiple covariate-adjusted analyses showed that the odds ratio (OR) for drug discontinuation was comparable between the secukinumab and TNFi switching groups [OR 1.136 (95% CI 0.843, 1.531) and 1.000 (95% CI 0.433-2.308), respectively]. The proportion of patients who achieved BASDAI50 was also comparable between the two groups [OR 0.833 (95% CI 0.481, 1.441) in PS-matched analysis]. Other clinical efficacy parameters were also comparable. In the subgroup analysis of AS patients with previous TNFi discontinuation due to ineffectiveness, all clinical efficacy parameters were comparable between the two groups. CONCLUSION: In AS patients with previous exposure to a TNFi, switching biologics to secukinumab and switching to an alternative TNFi resulted in comparable drug retention and clinical efficacy.

Factors associated with low trabecular bone scores in patients with end-stage kidney disease.

The trabecular bone score (TBS) is a textural index that indirectly assesses bone trabecular microarchitecture using lumbar spine images obtained by dual-energy X-ray absorptiometry (DXA). This study compared the TBS of patients with end-stage kidney disease (ESKD) with that of matched controls to identify risk factors associated with a low TBS. TBS and bone mineral density (BMD) were assessed in ESKD patients (n = 76) and age- and sex-matched control subjects (n = 76) using DXA. The TBS of both groups was then compared, and risk factors associated with a low TBS (defined as ≤ 1.31) were evaluated. The mean TBS in the ESKD group was significantly lower than that in the control group (1.34 ± 0.15 vs. 1.43 ± 0.08, respectively; p < 0.001). More subjects in the ESKD group had a low TBS [34.2% (ESRD) vs. 5.3% (controls); p < 0.001]. The TBS was negatively correlated with age, alkaline phosphatase and C-reactive protein levels, and dialysis vintage, and positively correlated with BMD at the lumbar spine, femoral neck, and hip. Multivariate analysis identified lower estimated glomerular filtration rate and increased C-reactive protein levels as being significantly associated with a low TBS. In conclusion, ESKD patients had abnormal bone microarchitecture (as assessed by the TBS). The TBS was positively correlated with BMD. Renal function and inflammatory marker levels were independently associated with a low TBS. Thus, TBS may be a useful clinical tool for assessing cancellous bone connectivity in ESKD patients.

Inflammation on spinal magnetic resonance imaging is associated with poor bone quality in patients with ankylosing spondylitis.

Objective: To determine the association between inflammatory lesions on spinal magnetic resonance imaging (MRI) and trabecular bone score (TBS) in patients with ankylosing spondylitis (AS). Methods: Ninety-seven patients with AS underwent spine MRI and dual energy X-ray absorptiometry of the lumbar spine to measure TBS and bone mineral density (BMD). Bone marrow edema (BME) on MRI was considered an inflammatory lesion. The presence, depth (>1 cm), and intensity of BME on MRI were scored for the 1st-4th lumbar spine segments. Inflammatory markers and spinal structural damage scores at the time of MRI examination were recorded. The association between inflammatory activity score on MRI and TBS was evaluated. Results: Among the 97 patients, 52 had BME on spinal MRI (L1-L4). The mean TBS values were 1.38 ± 0.11 and 1.43 ± 0.11 for patients with and without BME, respectively (p = .022). Total inflammatory activity scores on spinal MRI correlated negatively with TBS, but not with BMD. Patients with a TBS value representing a high fracture risk had more deep BME (>1 cm) (p = .048) on MRI. After adjustment for age, symptom duration, and lumbar spinal structural damage, the TBS decreased as inflammation severity on MRI increased (p = .026). Discussion: In AS patients, inflammation on spinal MRI was negatively correlated with TBS. The severity of local bone inflammation in the spine was associated with poor bone quality. These findings suggest that the control of active bone inflammation may be effective for preventing osteoporosis in AS patients.

Trabecular bone score as an assessment tool to identify the risk of osteoporosis in axial spondyloarthritis: a case-control study.

OBJECTIVES: To compare the trabecular bone score (TBS) between patients with axial spondyloarthritis (axSpA) and matched normal controls and identify risk factors associated with a low TBS. METHODS: TBS and BMD were assessed in the two groups (axSpA and control) using DXA. Osteoporosis risk factors and inflammatory markers were also assessed. Disease activity and radiographic progression in the sacroiliac joint and spine were evaluated in the axSpA group. Multivariate linear regression analysis was performed to identify risk factors associated with TBS. RESULTS: In the axSpA group, 248 subjects were enrolled; an equal number of age- and sex-matched subjects comprised the control group. The mean TBS was 1.43 (0.08) and 1.38 (0.12) in the control and axSpA groups, respectively (P < 0.001); BMD at the lumbar spine did not differ between the two groups. The TBS was negatively correlated with ESR and CRP levels in the axSpA group only (P < 0.001 and P = 0.007, respectively). Syndesmophytes in the axSpA group was associated with lower TBS (P < 0.001) but higher lumbar BMD (P = 0.021) vs controls. In the multivariate analyses, ESR, CRP and spinal radiographic progression were significantly associated with TBS. CONCLUSION: TBS assessments revealed poor bone quality in patients with axSpA compared with the matched controls. In axSpA, systemic inflammatory markers were negatively correlated with TBS and spinal radiographic progression and inflammatory markers were independently correlated with low TBS. TBS may, therefore, be a useful clinical tool to identify the risk of osteoporosis in patients with axSpA.

Associations between trabecular bone score and vertebral fractures in patients with axial spondyloarthritis.

OBJECTIVES: To compare trabecular bone scores (TBS) between axial SpA (axSpA) patients with and without vertebral fractures and investigate associations between TBS and vertebral fractures. METHODS: Two hundred and fifty-five patients fulfilling the imaging arm of the Assessment of SpondyloArthritis International Society axSpA criteria were enrolled. TBS and BMD were assessed using dual-energy X-ray absorptiometry. Vertebral fracture of the thoracic and lumbar spine was defined according to the Genant criteria. Osteoporosis risk factors, inflammatory markers, DAS and spinal structural damage were also assessed. Univariate logistic regression analysis was performed to identify factors associated with vertebral fractures. RESULTS: There were 31 vertebral fractures in 28/255 axSpA patients (11%). The mean (s.d.) TBS was 1.39 (0.11) and 1.30 (0.13) in patients without and with vertebral fractures, respectively (P < 0.001). BMD in the femoral neck was lower in patients with vertebral fractures (P = 0.027), but BMDs in the lumbar spine and total hip were not. Univariate logistic regression analyses identified old age (⩾50 years), TNF inhibitor treatment, the presence of syndesmophytes and a low TBS (<1.23) as associated with prevalent vertebral fractures [odds ratio (95% CI): 6.9 (2.0, 24.4), 2.4 (1.0, 5.5), 5.5 (2.2, 13.5) and 5.3 (2.0, 14.1), respectively]. TBS has a better discriminatory value than BMD at the total hip for prediction of vertebral fractures in axSpA patients (P = 0.034). CONCLUSION: Similar to individuals with primary osteoporosis, axSpA patients with vertebral fractures have a lower TBS. This suggests that TBS has the potential to predict future vertebral fractures in patients with axSpA.

Positive correlation between inflammation on sacroiliac joint MRI and serum C-terminal telopeptide of type-I collagen in ankylosing spondylitis but not in non-radiographic axial spondyloarthritis.

OBJECTIVES: To identify the clinical disease activity scores and laboratory markers that best reflect magnetic resonance imaging (MRI)-determined sacroiliac joint (SIJ) inflammation in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: This cross-sectional study included all consecutive patients who presented with axial spondyloarthritis in 2013-2015. All underwent SIJ MRI. The bone marrow oedema in the inflammatory lesions on MRI was scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide of type-I collagen (sCTX-I), and inflammatory markers were measured. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) were assessed. The correlations between the MRI-determined SIJ inflammation scores and disease activity scores and laboratory variables were evaluated. RESULTS: Of the 81 patients with axSpA, 45 had AS and 36 had nr-axSpA. The AS and nr-axSpA groups did not differ in terms of disease activity scores, physical functional index, or MRI-determined SIJ inflammation. Erythrocyte sedimentation rate, C-reactive protein, and ASDAS correlated with MRI inflammatory scores in nr-axSpA but not in AS. sCTX-I correlated with MRI-determined SIJ inflammatory scores in AS only. BASDAI and BALP levels did not associate with MRI inflammatory scores in either group. Multivariate analysis showed that sCTX-I associated independently with MRI inflammatory score in AS (ß=17.047, p=0.038). CONCLUSIONS: Inflammatory markers and ASDAS correlated with active sacroiliitis on MRI in nr-axSpA only. In AS, only sCTX-I correlated with active inflammation on SIJ MRI. sCTX-I may be useful as a marker of objective inflammation in AS.

Gender-Specific Associations between Low Skeletal Muscle Mass and Albuminuria in the Middle-Aged and Elderly Population.

Objective This study assessed gender-specific associations between low muscle mass (LMM) and albuminuria. Methods Data from the Korea National Health and Nutrition Examination Survey 2011 were employed. The study consisted of 1,087 subjects (≥50 years old). Skeletal muscle index (SMI) was defined as the weight-adjusted appendicular skeletal muscle mass. Mild LMM and severe LMM were defined as SMI that were 1-2 and >2 standard deviations below the sex-specific mean appendicular skeletal muscle mass of young adults, respectively. Increased albuminuria was defined as albumin-to-creatinine ratio ≥30mg/g Results Men with mild and severe LMM were significantly more likely to have increased albuminuria (15.2% and 45.45%, respectively) than men with normal SMI (9.86%, P<0.0001), but not women. Severe LMM associated independently with increased albuminuria in men (OR=7.661, 95% CI=2.72-21.579) but not women. Severe LMM was an independent predictor of increased albuminuria in hypertensive males (OR=11.449, 95% CI=3.037-43.156), non-diabetic males (OR=8.782, 95% CI=3.046-25.322), and males without metabolic syndrome (MetS) (OR=8.183, 95% CI=1.539-43.156). This was not observed in males without hypertension, males with diabetes or MetS, and all female subgroups. Conclusion Severe LMM associated with increased albuminuria in men, especially those with hypertension and without diabetes or MetS.

Radiographic progression is associated with increased cardiovascular risk in patients with axial spondyloarthritis.

OBJECTIVES: To compare the cardiovascular disease (CVD) risk between axial spondyloarthritis (axSpA) patients and matched controls, and to identify factors associated with increased CVD risk in axSpA patients. METHODS: This cross-sectional study enrolled 185 axSpA patients who fulfilled the Assessment for Spondyloarthritis (ASAS) criteria and 925 age- and sex-matched controls. None of the subjects had a previous history of CVD or diabetes mellitus. Traditional CVD risk factors were assessed and the 10-year CVD risk was calculated using the Framingham risk score (FRS). Estimated 10-year CVD risk was compared between axSpA patients and matched controls. Disease activity and radiographic progression in the sacroiliac joint and spine of axSpA patients were evaluated at the time of CVD risk assessment. RESULTS: High-density lipoprotein (HDL) cholesterol levels were lower in axSpA patients than in the matched controls (p = 0.004); however, systolic blood pressure was higher (p < 0.001). The FRS was 5.0 ± 6.6% for controls and 6.3 ± 8.7% for axSpA patients (p = 0.046). Both the grade of sacroiliitis on X-ray and the number of syndesmophytes correlated with the FRS (p = 0.009 and p = 0.001, respectively), but disease activity variables did not. The FRS was significantly higher in axSpA patients with a greater number of syndesmophytes (p = 0.035). Multivariate analysis identified the number of syndesmophytes as being independently associated with the FRS (p < 0.001). CONCLUSIONS: The FRS was higher in axSpA patients than in a matched general population. Radiographic progression in the spine was associated with a high estimated 10-year CVD risk.

Kimura disease complicated with bowel infarction and multiple arterial thromboses in the extremities.

Kimura disease (KD) is a chronic inflammatory disease characterized by slowly growing subcutaneous nodules in the face and the neck region. Although a concomitant hypercoagulable state can accompany KD, massive thromboses in patients with KD have rarely been reported. Here, we report a case of KD complicated with bowel infarction and multiple arterial thromboses in the upper and lower extremities. The patient underwent bowel resection and was successfully treated with corticosteroid and anticoagulation.

Value of multidetector computed tomography for the radiologic grading of sacroiliitis in ankylosing spondylitis.

The objective of this study is to investigate the value of multidetector computed tomography (MDCT) in the assessment of sacroiliitis in patients with established ankylosing spondylitis (AS). Paired plain radiographs and MDCT images of the 330 sacroiliac (SI) joints in 165 patients with definite or probable ankylosing spondylitis were analyzed for sacroiliitis. Sacroiliitis on plain radiographs were graded on a scale of 0-4 according to the modified New York (NY) criteria. For grading of sacroiliitis by MDCT, modified NY criteria were revised for MDCT application introducing the concept of quantification. The relationship between sacroiliitis grades by plain radiography and MDCT was analyzed by two radiologists, blinded for all clinical data. Of the 330 SI joints assessed, there was agreement between the sacroiliitis grading by plain radiography and MDCT in 73 (22.1 %) SI joints. Sacroiliitis grade by MDCT was higher in 250 (75.8 %) SI joints and lower in 7 (2.1 %) SI joints than that by plain radiography. Using the MDCT, 83.6 % of patients met the modified NY radiologic criteria for the classification of AS, compared with 58.2 % of the patients by plain radiography. Twenty-six percent of the patients, who did not meet the modified NY criteria for the classification of AS by plain radiography, met the criteria by MDCT. Disease durations in patients with grade 2 and grade 3 sacroiliitis were significantly shorter in patients evaluated by MDCT compared with plain radiography. MDCT is a useful imaging method that can be applied to the initial diagnosis of the AS, and by better visualization of SI joint changes, it can be used to predict the progress of the disease.

The effects of antihypertensive drugs on bone mineral density in ovariectomized mice.

The effects of several antihypertensive drugs on bone mineral density (BMD) and micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight-week-old female C57/BL6 mice were used for this study. Three days after ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg), telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all mice was confirmed to evaluate estrogen deficiency state. BMD and micro-architectural analyses were performed on tibial proximal ends by micro-computed tomography (micro-CT). When OVX mice with uterine atrophy were compared with mice without atrophy, BMD decreased (P < 0.001). There were significant differences in BMD loss between different antihypertensive drugs (P = 0.005). Enalapril and propranolol increased BMD loss in mice with atrophied uteri compared with control mice. By contrast, thiazide increased BMD in mice with uterine atrophy compared with vehicle-treated mice (P = 0.048). Thiazide (P = 0.032) and telmisartan (P = 0.051) reduced bone loss and bone fraction in mice with uterine atrophy compared with the control. Thiazide affects BMD in OVX mice positively. The reduction in bone loss by thiazide and telmisartan suggest that these drugs may benefit menopausal women with hypertension and osteoporosis.

Costovertebral joint involvement in patients with axial spondyloarthritis.

OBJECTIVES: To evaluate costovertebral joint involvement in patients with axial spondyloarthritis (axSpA) and to assess its association with disease features. METHODS: We included 150 patients from the Incheon Saint Mary's axSpA observational cohort who underwent whole spine low-dose computed tomography (ldCT). Costovertebral joint abnormalities were scored by two readers on a scale of 0-48 based on the presence or absence of erosion, syndesmophyte, and ankylosis. The interobserver reliability of costovertebral joint abnormalities was assessed using intraclass correlation coefficients (ICCs). Associations between costovertebral joint abnormality scores and clinical variables were evaluated using a generalized linear model. RESULTS: Two independent readers found costovertebral joint abnormalities in 74 (49%) patients and 108 (72%) patients. The ICCs of scores for erosion, syndesmophyte, ankylosis, and total abnormality were 0.85, 0.77, 0.93, and 0.95, respectively. For both readers, total abnormality score was correlated with age, symptom duration, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS functional index (BASFI), CT syndesmophyte score (CTSS), and number of bridging spines. Multivariate analyses showed age, ASDAS, CTSS to be independently associated with total abnormality scores in both readers. The frequency of ankylosed costovertebral joint was 10.2% (reader 1) and 17.0% (reader 2) in patients without radiographic syndesmophytes (n=62), and 10.3% (reader 1) and 17.2% (reader 2) in patients without radiographic sacroiliitis (n=29). CONCLUSIONS: Costovertebral joint involvement was common in patients with axSpA, even in the absence of radiographic damage. LdCT is recommended for evaluating structural damage in patients with clinically suspected costovertebral joint involvement.

Prevalence and Associated Factors of Facet Joint Ankylosis in Patients With Axial Spondyloarthritis.

OBJECTIVE: To investigate the prevalence of facet joint ankylosis in the whole spine in axial spondyloarthritis (axSpA) using low-dose computed tomography (LDCT), and to identify factors associated with facet joint ankylosis. METHODS: Whole spine LDCT images from 161 patients with axSpA were examined, and the presence of facet joint ankylosis was assessed (right and left, C2-S1) by 2 readers. Facet joint ankylosis was scored from 0 to 46. Structural damage of vertebral body was assessed using CT Syndesmophyte Score (CTSS). Factors associated with ankylosed facet joint scores for the whole spine were identified using a generalized linear model with a negative binomial distribution. RESULTS: Seventy-nine patients (49%) and 70 patients (43%; reader 1 and reader 2, respectively) had ≥ 1 ankylosed facet joint. Facet joint ankylosis was most common in the thoracic spine. The mean score of facet joint ankylosis for the whole spine was 6.6 (SD 11.2) in reader 1 and 4.2 (SD 8.4) in reader 2. Whole spine facet joint ankylosis score positively correlated with Ankylosing Spondylitis Disease Activity Score (ASDAS) and CTSS. In multivariable analysis, the ankylosed facet joint score was associated with ASDAS, sacroiliitis, CTSS, and a history of uveitis in both readers. Uveitis history, ASDAS, and CTSS were associated with whole spine facet joint ankylosis score in subgroup analysis of only radiographic axSpA. CONCLUSION: The prevalence of ankylosed facet joints is high in axSpA, especially in the thoracic segment. The whole spine ankylosed facet joint score is significantly associated with a history of uveitis, ASDAS, sacroiliitis, and syndesmophyte score.

Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti-tumor necrosis factor therapy.

(1) To compare the serum levels of Dickkopf-1 (DKK-1) and bone biomarkers in patients with ankylosing spondylitis (AS) and healthy controls. (2) To examine the effects of anti-tumor necrosis factor-α (TNF-α) therapy for 3 months on bone biomarkers in patients with AS. We measured the levels of DKK-1, osteocalcin, osteoprotegerin, and C-terminal telopeptide of type I collagen (CTX-1) in patients with AS and in healthy controls at baseline and 3 months after initiating anti-TNF-α therapy in AS patients. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were also measured before and after anti-TNF-α therapy in AS patients. Serum levels of DKK-1 were significantly lower in the AS patients than in the controls (P < 0.0001). Osteocalcin and osteoprotegerin levels were significantly higher in the AS patients than in the controls (P < 0.0001). Serum levels of DKK-1 were not changed after the 3-month anti-TNF-α therapy. Osteocalcin level increased (P < 0.0001), osteoprotegerin level and BASDAI scores decreased (P = 0.025 and P < 0.0001, respectively) significantly after the 3-months anti-TNF-α therapy. Serum DKK-1 level was lower in patients with AS than in healthy controls and did not change after 3 months of anti-TNF-α therapy in the AS patients despite the marked improvement in BASDAI scores. These findings suggest the low serum DKK-1 level is related to the pathogenesis of new bone formation in AS, which is resistant to TNF-α blocking therapy.

Induction of remission is difficult due to frequent relapse during tapering steroids in Korean patients with polymyalgia rheumatica.

Polymyalgia rheumatica is an inflammatory disease affecting elderly and involving the shoulder and pelvic girdles. No epidemiological study of polymyalgia rheumatica was conducted in Korea. We retrospectively evaluated patients with polymyalgia rheumatica followed up at the rheumatology clinics of 10 tertiary hospitals. In total 51 patients, 36 patients (70.6%) were female. Age at disease onset was 67.4 yr. Twenty-three patients (45.1%) developed polymyalgia rheumatica in winter. Shoulder girdle ache was observed in 45 patients (90%) and elevated erythrocyte sedimentation rate (> 40 mm/h) in 49 patients (96.1%). Initial steroid dose was 23.3 mg/d prednisolone equivalent. Time to normal erythrocyte sedimentation rate was 4.1 months. Only 8 patients (15.7%) achieved remission. Among 41 patients followed up, 28 patients (68.3%) had flare at least once. Number of flares was 1.5 ± 1.6. The frequency of flare was significantly lower in patients with remission (P = 0.02). In Korea, polymyalgia rheumatica commonly develops during winter. Initial response to steroid is fairly good, but the prognosis is not benign because remission is rare with frequent relapse requiring long-term steroid treatment.

Physical activity is associated with physical and global function in patients with axial spondyloarthritis, independent of disease activity.

OBJECTIVES: To investigate whether physical activity is independently associated with physical and global function in patients with axial spondyloarthritis (axSpA), and to analyse the relationship between subtypes of physical activity (work, transport, and recreation) and functional impairment. METHODS: One-hundred-and-eighty-five patients were included. Physical function was assessed using BASFI, and global function was assessed using the ASAS health index (HI). Physical activity was measured using the Global Physical Activity Questionnaire. Levels of physical activity were categorised as low, moderate or high. The associations between levels of physical activity and the BASFI and ASAS HI scores were analysed using multivariate regression analysis. RESULTS: Of the 185 patients, 46, 63 and 76 reported low, moderate and high levels of physical activity, respectively. There was a negative correlation between the BASFI and total physical activity. Multivariate linear regression analysis revealed that a high level of physical activity was independently associated with BASFI after adjusting for age, ASDAS. sacroiliitis and syndesmophyte number (ß (95% CI) =-0.88 (-1.49--0.26); p=0.006). One-hundred-and-forty-six had good global functioning (ASAS HI≤5). Multivariate logistic regression analysis revealed that moderate physical activity was independently associated with good global functioning (OR (95% CI) = 2.82 (1.02-7.86); p = 0.047). Recreational activity, but not work- and transport-related activity, showed a significant relationship with ASAS HI scores (ß (95% CI) =-0.55 (-1.02-0.08); p = 0.023). CONCLUSIONS: Physical activity in those with axSpA is associated independently with physical and global functioning. Among the subtypes of physical activity, recreational activity is related to global functioning.

Increased risks of aortic regurgitation and atrial fibrillation in radiographic axial spondyloarthritis patients: a 10-year nationwide cohort study.

Background: To compare the incidences of aortic regurgitation, atrial fibrillation (AF), and atrioventricular (AV) block II-III between radiographic axial spondyloarthritis (r-axSpA) patients and the general population (GP). Methods: National Health Insurance Services data were used. R-axSpA patients (N = 8877) and the age- and sex-matched GP (N = 26,631) were followed from August 2006 to December 2019. Incidence rates and standardized incidence ratios (SIRs) of aortic regurgitation, AF, and AV block II-III were compared between these groups. Ten-year incidence rates and hazard ratios (HRs) were calculated by the Kaplan-Meier method and Cox regression analysis. Results: Incidence rates of aortic regurgitation, AV block II-III, and AF in the r-axSpA group were 0.42, 0.21, and 4.0 per 1000 person-years (PYs), respectively. In the r-axSpA group, the SIR for aortic regurgitation was highest among 40- to 49-year-old men (4.11). Incidence rates of aortic regurgitation and AF were higher in the r-axSpA group than in the GP group (0.42 versus 0.18 per 1000 PYs 4.00 versus 3.13 per 1000 PYs, both p < 0.001, respectively), whereas the difference was insignificant for AV block II-III (0.21 versus 0.14 per 1000 PYs, p = 0.222). In multivariate analysis, r-axSpA was associated with a higher hazard (risk) for the development of aortic regurgitation and AF [HR (95% confidence interval) = 2.55 (1.49-4.37) and 1.20 (1.04-1.39), respectively], but the difference was insignificant for AV block II-III [HR (95% confidence interval) = 1.17 (0.59-2.31)]. Conclusions: Compared with the GP, r-axSpA patients are at increased risk of aortic regurgitation and AF, but not AV block II-III. These patients should be carefully monitored for occurrence of aortic regurgitation and AF.

Measurement of interleukin-33 (IL-33) and IL-33 receptors (sST2 and ST2L) in patients with rheumatoid arthritis.

The interleukin-33 (IL-33)/ST2 pathway has emerged as an intercellular signaling system that participates in antigen-allergen response, autoimmunity and fibrosis. It has been suggested that IL-33/ST2 signaling has been involved in the pathogenesis of rheumatoid arthritis (RA), because IL-33 and its receptor have been specifically mapped to RA synovium. The aim of this study was to determine the levels of IL-33 and sST2 in sera and synovial fluids in patients with RA. The serum level of IL-33 was significantly higher in patients with RA (294.9 ± 464.0 pg/mL) than in healthy controls (96.0 ± 236.9 pg/mL, P = 0.002). The synovial fluid level of IL-33 was significantly higher in RA patients than in osteoarthritis patients. The level of serum sST2 was higher in RA patients than in healthy controls (P = 0.042). A significant relationship was found between the levels of IL-33 and IL-1ß (r = 0.311, P = 0.005), and IL-33 and IL-6 (r = 0.264, P = 0.017) in 81 RA patients. The levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naïve RA. Conclusively, IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA.