Sex-specific impact of inflammation on traditional cardiovascular risk factors and atherosclerosis in axial spondyloarthritis. A multicentre study of 913 patients.

INTRODUCTION: The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed. METHODS: Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment. RESULTS: After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (ß coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (ß coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis. CONCLUSION: Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.

Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis.

OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.

Factors associated with discontinuation of biologics in patients with inflammatory arthritis in remission: data from the BIOBADASER registry.

BACKGROUND: The objectives of this study were to assess the discontinuation of biologic therapy in patients who achieve remission and identify predictors of discontinuation of biologics in patients with inflammatory arthritis in remission. METHODS: An observational retrospective study from the BIOBADASER registry comprising adult patients diagnosed with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) and receiving 1 or 2 biological disease-modifying drugs (bDMARDs) between October 1999 and April 2021. Patients were followed yearly after initiation of therapy or until discontinuation of treatment. Reasons for discontinuation were collected. Patients who discontinued bDMARDs because of remission as defined by the attending clinician were studied. Predictors of discontinuation were explored using multivariable regression models. RESULTS: The study population comprised 3,366 patients taking 1 or 2 bDMARDs. Biologics were discontinued owing to remission by 80 patients (2.4%): 30 with RA (1.7%), 18 with AS (2.4%), and 32 with PsA (3.9%). The factors associated with a higher probability of discontinuation on remission were shorter disease duration (OR: 0.95; 95% CI: 0.91-0.99), no concomitant use of classic DMARDs (OR: 0.56; 95% CI: 0.34-0.92), and shorter usage of the previous bDMARD (before the decision to discontinue biological therapy) (OR: 1.01; 95% CI: 1.01-1.02); in contrast, smoking status (OR: 2.48; 95% CI: 1.21-5.08) was associated with a lower probability. In patients with RA, positive ACPA was associated with a lower probability of discontinuation (OR: 0.11; 95% CI: 0.02-0.53). CONCLUSIONS: Discontinuation of bDMARDs in patients who achieve remission is uncommon in routine clinical care. Smoking and positive ACPA in RA patients were associated with a lower probability of treatment discontinuation because of clinical remission.

Depression and anxiety in systemic lupus erythematosus: A case-control study on prevalence and associated factors in a single-center cohort.

OBJECTIVES: To evaluate the prevalence of self-perceived depression and anxiety in patients with systemic lupus erythematosus (SLE) and to explore associated factors. METHODS: Cross-sectional study of unselected patients with SLE (ACR-97 criteria) and controls with chronic inflammatory rheumatic diseases. Both completed the Hospital Anxiety and Depression Scale (HADS). Demographic and clinical characteristics, comorbidity, and treatments were collected, and a multivariate analysis was performed to explore factors associated with depression and anxiety in SLE. RESULTS: The study population comprised 172 patients and 215 controls. Women accounted for 93% of the patients with SLE. Fibromyalgia was recorded in 12.8% and a history of depression in 17%. According to HADS, 37.2% fulfilled the diagnostic criteria for depression and 58.7% those for anxiety; prevalence was similar in the controls (32.6% and 55.1%, respectively). Up to a third of patients with self-perceived depression were not receiving antidepressants. There was no concordance between a previous history of depression and current depression. In the multivariate model, current depression was associated with single marital status (OR 2.69; 95% CI: 1.17-6.42; p = .022), fibromyalgia (7.69; 2.35-30.72; p = .001), smoking (3.12; 1.24-8.07; p = .016), severity of SLE (0.76; 0.6-0.94; p = .016), and organ damage (1.27; 1.01-1.61; p = .042). Current anxiety was only associated with fibromyalgia (3.97; 1.21-17.98; p = .036). CONCLUSIONS: Depression and anxiety are most likely underdiagnosed in SLE. Prevalence appears to be similar to that of other chronic inflammatory rheumatic diseases. Anxiety is associated with fibromyalgia, while depression is also associated with single marital status, smoking, organ damage, and severity of SLE.

Sex differences in cardiovascular and disease-related features in axial spondyloarthritis. A multicenter study of 912 patients.

OBJECTIVES: To determine the potential impact of sex-specific disease-related characteristics on cardiovascular (CV) disease in axial spondyloarthritis (axSpA). METHODS: Cross-sectional study of the Spanish AtheSpAin cohort to study CV disease in axSpA. Data on carotid ultrasound and CV disease and disease-related features were collected. RESULTS: 611 men and 301 women were recruited. Classic CV risk factors were significantly less prevalent in women, who also showed a lower frequency of carotid plaques (p = 0.001), lower carotid intima-media thickness (IMT) values ​​(p<0.001) and CV events (p = 0.008). However, after adjustment for classic CV risk factors, only the differences with respect to carotid IMT remained statistically significant. Women showed higher ESR at diagnosis (p = 0.038), and more active disease (ASDAS, p = 0.012, and BASDAI, p<0.001). They had shorter disease duration (p<0.001), lower prevalence of psoriasis (p = 0.008), less structural damage (mSASSS, p<0.001), and less mobility limitation (BASMI, p = 0.033). To establish whether these findings could lead to sex differences in CV disease burden, we compared the prevalence of carotid plaques in men and women with the same level of CV risk stratified according to the Systematic Coronary Risk Evaluation (SCORE). Men included in the low-moderate CV risk SCORE category had more carotid plaques (p = 0.050), along with longer disease duration (p = 0.004), higher mSASSS (p = 0.001) and psoriasis (p = 0.023). In contrast, in the high-very high-risk SCORE category, carotid plaques were observed more frequently in women (p = 0.028), who were characterized as having worse BASFI (p = 0.011), BASDAI (p<0.001) and ASDAS (p = 0.027). CONCLUSION: Disease-related features may influence the expression of atherosclerosis in patients with axSpA. This may be especially applicable to women at high CV risk, characterized by greater disease severity and more severe subclinical atherosclerosis than men, suggesting a stronger interaction between disease activity and atherosclerosis in women with axSpA.

Effects of COVID-19 vaccination on disease activity in patients with rheumatoid arthritis and psoriatic arthritis on targeted therapy in the COVIDSER study.

OBJECTIVE: To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies. PATIENTS AND METHODS: 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model. RESULTS: The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i. CONCLUSION: COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation.

Cardiovascular and disease-related features associated with extra-articular manifestations in axial spondyloarthritis. A multicenter study of 888 patients.

OBJECTIVES: To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA). METHODS: This is a cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected. RESULTS: 888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs. CONCLUSION: Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids.

Implications of FRAX® adjusted for recent fracture on the indication of treatment in an FLS.

We analyzed the practical consequences of applying an adjusted FRAX® for recent fractures in a FLS. After analyzing 2777 patients, we concluded that the adjusted FRAX® is irrelevant when calculating FRAX® with DXA and is only useful for fractures of the humerus when DXA is not available. PURPOSE: A FRAX® adjusted to fractures less than 2 years old has been proposed. The objective of this work was to analyze the clinical implications of applying the adjusted FRAX® instead of the classic FRAX® in a fracture liaison service (FLS) unit. METHODS: Adults aged 50 years or older with fragility fractures (hip, spine, humerus, and forearm) that occurred in the 12 months prior to the baseline visit were included. We recorded demographic data, type of fracture, DXA, classic FRAX®, and FRAX® adjusted for recent fractures and indications for anti-osteoporotic medication (AOM) following the guidelines of the Spanish Society of Rheumatology. RESULTS: A total of 2777 patients were included, mean age 73 years, 84% women. The type of fracture was as follows: forearm (n = 958; 34.5%), hip (n = 781; 28.1%), humerus (n = 642; 23.1%), and spine (n = 397, 14.3%). DXA was performed in 2134 cases (76.8%). A total of 2522 patients (90.8%) were candidates for AOM (100% involving the hip and spine, 83% forearm, and 85% humerus). FRAX®-hip ≥ 3% increased from 1601 to 1775 cases (57.6 to 64%). The average FRAX®-hip (SD) increased from 5.7 (6) to 7.5 (9) (4.6 to 8.8 in males and 5.9 to 7.3 in females). The percentage of forearm fracture candidates for AOM, with or without DXA, did not change after FRAX®-hip adjustment, while the number of patients with humerus fractures increased from 59 to 80% in those who did not have DXA. In the entire sample, FRAX®-adjusted led to an indication of AOM for 15 additional patients (0.5% of major fractures): 14 with a humerus fracture and 1 with a forearm fracture. CONCLUSIONS: The adjusted FRAX® for recent fractures in an FLS unit in an adjusted FRAX® is irrelevant when calculating FRAX® with DXA; in fact, it is only useful for fractures of the humerus when DXA is not available.

Irisin as a Novel Biomarker of Subclinical Atherosclerosis, Cardiovascular Risk and Severe Disease in Axial Spondyloarthritis.

Introduction: Patients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients. Methods: A large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA. Results: Low irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ≥4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p<0.001) and negatively correlated with visual analogue scale and Bath Ankylosing Spondylitis Metrology Index (p<0.05 in all the cases). Moreover, lower irisin levels were observed in patients with sacroiliitis and in those with a negative HLA-B27 status (p<0.001 and p=0.006, respectively), as well as in those treated with non-steroidal anti-inflammatory drugs and conventional disease-modifying antirheumatic drugs (p<0.001 and p=0.002, respectively). Interestingly, the TT genotype and the T allele of rs16835198 were less frequent in axSpA patients with ASDAS >2.1 (Odds Ratio (OR): 0.48 [0.28-0.83] and OR: 0.73 [0.57-0.92], respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 [1.08-1.97], p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 [1.13-2.66], p=0.01). Conclusions: Our results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA.

Factors associated with atherosclerosis in radiographic and non-radiographic axial spondyloarthritis. A multicenter study on 838 patients.

OBJECTIVES: To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA). METHODS: This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection. RESULTS: 639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients. CONCLUSION: Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA.

Long-term persistence of treatment after hip fracture in a fracture liaison service.

Long-term adherence to antiosteoporosis medication (AOM) in the setting of a fracture liaison service (FLS) are not well known. Patients ≥ 50 with hip fracture seen in an FLS and recommended for treatment to prevent new fractures were analyzed. Baseline data included demographics, identification mode, previous treatment and FRAX items. Patient records were reviewed 3-8 years later, and these data were collected: (1) survival; (2) major refracture; (3) initiation of treatment, proportion of days covered (PDC) and persistence with AOM. 372 patients (mean age, 79 years; 76% women) were included. Mean follow-up was 47 months, 52 patients (14%) had a refracture (22 hip) and 129 (34.5%) died. AOM was started in 283 patients (76.0%). Factors associated with initiation of AOM were previous use of bisphosphonate (OR 9.94; 95% CI 1.29-76.32) and a lower T-score lumbar (OR 0.80; 95% CI 0.65-0.99). Persistence decreased to 72.6%, 60% and 47% at 12, 36 and 60 months. A PDC > 80% was confirmed in 208 patients (55.7%) and associated with previous use of bisphosphonate (OR 3.38; 95% CI 1.34-8.53), treatment with denosumab (OR 2.69; 95% CI:1.37-5.27), and inpatient identification (OR 2.26; 95% CI 1.18-4.34). Long-term persistence with AOM was optimal in patients with hip fracture seen at an FLS. A PDC > 80% was associated with inpatient identification and prescription of denosumab.

Real-World Effectiveness and Treatment Retention of Secukinumab in Patients with Psoriatic Arthritis and Axial Spondyloarthritis: A Descriptive Observational Analysis of the Spanish BIOBADASER Registry.

Rheumatic diseases are extensively managed with biological disease-modifying antirheumatic drugs (bDMARDs), but a notable proportion of patients withdraw in the long term because of lack of effectiveness, adverse events, or the patient's decision. The present real-world analysis showed the effectiveness, retention, and safety data collected in the Spanish BIOBADASER registry for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA, including ankylosing spondylitis (AS) and non-radiographic axSpA) treated with secukinumab, a human antibody against interleukin-17A (IL-17A), for more than 12 months. Six hundred and thirty-nine patients were analysed (350, 262, and 27 PsA, AS, and nr-axSpA patients, respectively). The results showed an improvement in the disease activity after 1 year of treatment, in terms of decreases of the mean Disease Activity Score 28 using C-reactive protein (DAS28-CRP), the mean Disease Activity Psoriatic Arthritis (DAPSA) score, swollen joint counts (SJC), and tender joint counts (TJC) in PsA patients and decreases in the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the mean Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. This improvement was maintained or increased after 2 and 3 years of treatment, indicating that secukinumab is effective in both naïve and non-responder patients. Retention rates were higher when secukinumab was used as the first-line biological treatment, although they were also adequate in the second and third lines of treatment. Collected safety data were consistent with previous reports.

Potential relation of cardiovascular risk factors to disease activity in patients with axial spondyloarthritis.

BACKGROUND: Axial spondyloarthritis (axSpA) patients are known to have a higher prevalence of several comorbidities, including, among others, an increased risk of atherosclerosis, hypertension, dyslipidemia, and diabetes. The purpose of the present study was to determine whether the sum of traditional cardiovascular (CV) risk factors is related to disease characteristics, such as disease activity, in patients with axSpA. METHODS: A cross-sectional study that encompassed 804 patients with axSpA was conducted. Patients were assessed for the presence of five traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking status), and disease activity measurements. A multivariable regression analysis was performed to evaluate whether the number of classic CV risk factors was independently associated with specific features of the disease, to include disease activity. RESULTS: A multivariable analysis showed that Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP) activity score was significantly higher in patients with 1 [beta coefficient 0.3 (95% confidence interval (CI) 0.1-0.5), p = 0.001] and ⩾2 [beta coefficient 0.5 (95% CI 0.3-0.7), p = 0.000] CV risk factors compared with those without CV risk factors. Similarly, patients with 1 [OR 2.00 (95%CI 0.99-4.02), p = 0.053] and ⩾2 [OR 3.39 (95%CI 1.82-6.31), p = 0.000] CV risk factors had a higher odds ratio for the presence of high disease activity compared with the zero CV category. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) activity score was significantly associated with the number of CV risk factors, being higher in patients with more CV risk factors. These relationships showed a CV risk factor-dependent effect being beta coefficients and ORs higher for the effect of ⩾2 over 1 CV risk factor. CONCLUSION: Among patients with axSpA, as the number of traditional CV risk factors increased, disease activity similarly increases in an independent manner.

Vaspin in atherosclerotic disease and cardiovascular risk in axial spondyloarthritis: a genetic and serological study.

BACKGROUND: Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA). Given the high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients, we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce. For this reason, we aimed to evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA. METHODS: This study included 510 patients diagnosed with axSpA. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242, rs7159023, and rs35262691) were genotyped by TaqMan probes. Serum vaspin levels were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed using STATA® v.11.1. RESULTS: Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (p < 0.05). At the genetic level, we disclosed that the minor allele of rs2236242 (A) was associated with lower serum vaspin levels in axSpA, while the rs7159023 minor allele (A) was linked to higher serum levels (p < 0.05). When the three polymorphisms assessed were combined conforming haplotypes, we disclosed that the TGC haplotype related to high serum levels of vaspin (p = 0.01). However, no statistically significant association was observed between vaspin and markers of subclinical atherosclerosis, both at the genetic and serological level. CONCLUSIONS: Our results revealed that vaspin is linked to CV risk factors that may influence on the atherosclerotic process in axSpA. Additionally, we disclosed that serum vaspin concentration is genetically modulated in a large cohort of patients with axSpA.

Fracture liaison service model: treatment persistence 5 years later.

We analyzed the long-term persistence of treatment in a FLS. During follow-up, 15.2% of patients had a refracture and 23.8% died. At the 5-year checkup, 74% had started treatment (associated with female sex, previous use of bisphosphonate, and referral to an osteoporosis clinic). Persistence at 1 and 5 years was 70.6% and 46.5%, respectively. INTRODUCTION: To analyze the long-term persistence of treatment in a fracture liaison service (FLS). METHODS: Patients ≥ 50 years with a fragility fracture attended between 2012 and 2016 who were recommended for treatment to prevent new fractures were included. Baseline data included demographics, type of fracture, previous treatment, and FRAX® items. Five years later, patient records were reviewed and the following data were collected: [1] survival; [2] refracture; [3] initiation of treatment, persistence, and medication possession ratio (MPR) > 80%. RESULTS: We included 888 patients, mean age 75 years, 83% women, and mean follow-up 56 months. During follow-up, 135 patients (15.2%) had a refracture (109 major fractures, 50 hip refractures) and 212 patients died (23.8%); at the 5-year checkup, 657 patients (74%) had started some type of treatment. Factors associated with the start of treatment were female sex (OR 2.10; 95% CI: 1.42-3.11), previous use of bisphosphonate (OR 3.91; 95% CI: 2.23-6.86), and referral to an osteoporosis clinic (OR 1.46; 95% CI: 1.02-2.07). Persistence decreased from 70.6% at 12 months to 46.5% at 60 months. An MPR > 80% was confirmed in 449 patients, 68.3% of whom were under treatment. A total of 521 and 447 patients received treatment for at least 24 and 36 months, respectively (79.3% and 68.0% of those who started treatment). CONCLUSIONS: Patients with fragility fractures attended at an FLS showed optimal long-term persistence of treatment. These data can help healthcare managers better calculate the cost-effectiveness of implementing the FLS model.

Subclinical atherosclerotic disease in ankylosing spondylitis and non-radiographic axial spondyloarthritis. A multicenter study on 806 patients.

OBJECTIVES: To compare the atherosclerosis disease burden between ankylosing spondylitis (AS) and non-radiographic (nr) axial spondyloarthritis (axSpA) and establish a model that allows to identify high-cardiovascular (CV) risk in axial spondyloarthritis patients. METHODS: Cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort aimed to study atherosclerosis in axSpA. Carotid ultrasound (US) was performed to determine the carotid intima-media wall thickness (cIMT) and detect the presence of carotid plaques. The European cardiovascular disease risk assessment model, the Systematic COronary Risk Evaluation (SCORE), was also applied. RESULTS: A set of 639 patients with AS and 167 patients with nr-axSpA without history of CV events were recruited. AS patients were older showing more CV risk factors and higher values of C reactive protein and erythrocyte sedimentation rate (ESR) than those with nr-axSpA. However, no difference in the prevalence of carotid plaques or in the cIMT was found between both groups in the adjusted analysis. The percentage of patients reclassified from the low and moderate CV risk categories to the very high-risk category due to the presence of carotid plaques was comparable in AS and nr-axSpA (10.7% versus 10.1% and 40.5% versus 45.5%, respectively). A model containing age, BASFI and ESR applied to moderate risk axSpA patients identified 41% of these patients as having very high-risk patients with high specificity (88%). CONCLUSION: The atherosclerosis burden is similar in nr-axSpA and AS. As occurred for AS, more than 40% of axSpA patients included in the category of moderate CV risk according to the SCORE are reclassified into very high risk after carotid US, and a clinically relevant proportion of them can be detected by applying a model containing age, BASFI and ESR.

Association of Gender, Diagnosis, and Obesity With Retention Rate of Secukinumab in Spondyloarthropathies: Results Form a Multicenter Real-World Study.

Background: Secukinumab has been shown effective for psoriatic arthritis (PsA) and axial spondylarthritis (AxSpA) in randomized trials. The aim of this study was to analyze baseline patient and disease characteristics associated with a better retention rate of secukinumab under real-world conditions. Patients and Methods: Real-life, prospective multicenter observational study involving 138 patients, 61 PsA and 77 AxSpA, who were analyzed at baseline, 6, 12 months and subsequently every year after starting secukinumab regardless of the line of treatment. Demographics and disease characteristics, measures of activity, secukinumab use, and adverse events were collected. Drug survival was analyzed using Kaplan-Meier curves and factors associated with discontinuation were evaluated using Cox regression. The machine-learning J48 decision tree classifier was also applied. Results: During the 1st year of treatment, 75% of patients persisted with secukinumab, but accrued 71% (n = 32) in total losses (n = 45). The backward stepwise (Wald) method selected diagnosis, obesity, and gender as relevant variables, the latter when analyzing the interactions. At 1 year of follow-up, the Cox model showed the best retention rate in the groups of AxSpa women (95%, 95% CI 93-97%) and PsA men (89%, 95% CI 84-93%), with the worst retention in PsA women (66%, 95% CI 54-79%). The J48 predicted secukinumab retention with an accuracy of 77.2%. No unexpected safety issues were observed. Conclusions: Secukinumab shows the best retention rate at 1 year of treatment in AxSpA women and in PsA men, independently of factors such as the time of disease evolution, the line of treatment or the initial dose of the drug.

Proprotein convertase subtilisin/kexin type 9 in the dyslipidaemia of patients with axial spondyloarthritis is related to disease activity.

OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism and has been linked to cardiovascular (CV) risk. The purpose of the present study was to examine whether PCSK9 levels are related to abnormalities in the lipid profile and the development of atherosclerosis that occurs in patients with axial SpA (axSpA). METHODS: We performed a cross-sectional study that encompassed 545 individuals; 299 patients with axSpA and 246 statin use-matched controls. PCSK9 and standard lipid profiles were analysed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the influence of PCSK9 on axSpA-related dyslipidaemia and subclinical carotid atherosclerosis. RESULTS: Total cholesterol, high-density lipoprotein and low density lipoprotein cholesterol, lipoprotein (a) and apolipoprotein A1 were significantly lower in axSpA patients than controls. PCSK9 serum levels [ß coefficient -44 ng/dl (95% CI -60, -27), P = 0.000] were also downregulated in axSpA patients after fully multivariable adjustment. ASDAS-CRP was found to be independently and significantly related to PCSK9 [ß coefficient 10 ng/dl (95% CI 1, 18), P = 0.023] after analysing fully adjusted models that took age, sex and the rest of the lipid profile molecules into account. Whereas patients taking prednisone showed higher serum levels of PCSK9 [55 ng/ml (95% CI 24, 8), P = 0.001], those under anti-TNF-α therapies exhibited lower levels [ß coefficient -26 ng/ml (95% CI -43, -9], P = 0.003]. CONCLUSION: PCSK9 is downregulated in patients with axSpA. Disease activity is positive and significantly related to PSCK9. Anti-TNF-therapy yields a reduction in PCSK9 serum levels.