Long-Term Survival of Subcutaneous Biosimilar Tumor Necrosis Factor Inhibitors Compared to Originators: Results From a Multicenter Prospective Registry.

OBJECTIVE: To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. METHODS: Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. RESULTS: A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. CONCLUSION: No significant differences were found between treatments in long-term survival due to inefficacy or AEs.

Osteoporosis in psoriatic arthritis: Risk factors, insufficiency fractures and its association with the disease activity.

OBJECTIVE: The prevalence of osteoporosis (OP) and insufficiency fractures in psoriatic arthritis (PsA) remains controversial. The aim of this study was to describe the prevalence of OP and insufficiency fractures in a representative cohort of patients with PsA, and to analyse its association with general risk factors and characteristics of the psoriatic disease in our geographical area. METHODS: Multi-centric, descriptive study of patients with PsA. We recorded clinical characteristics, as well as protective and risk factors for OP and insufficiency fractures. Hip and lumbar densitometry and lateral X-ray of the spine were evaluated. Descriptive statistics for OP and risk factors were calculated. The patients with OP were compared to those without by univariate analyses, and results were adjusted by age and sex. The association of OP and fractures with clinical characteristics was analysed by logistic regression. RESULTS: 166 patients (50 men; 116 women) were included. OP was present in 26.5%, and it was more frequent in women and patients above 50 years old. Insufficiency fractures occurred in 5.4% of the total sample. In the logistic regression, OP was associated with age over 50 [OR 3.7; 95% CI (1.2-11.6); p=.02]. No association with clinical parameters was found. The most frequent risk factors among patients with OP were vitamin D insufficiency, sedentary behaviour, low calcium intake, and active smoking. In the logistic regression, OP was associated with early menopause [OR 11.7; 95% CI (1.29-106.0); p=.029] and sedentary behaviour [OR 2.3; 95% CI (1.0-5.2); p=.049]. CONCLUSIONS: In patients with PsA, OP is more frequent in women and patients over 50 years old. A sedentary lifestyle and early menopause may add extra risk for OP. Type, duration disease, and treatments are not associated with OP or insufficiency fractures.

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.

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.

Human papilloma virus screening: evaluation of testing and surveillance in rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus.

BACKGROUND AND OBJECTIVES: Immunosuppression is a known risk factor for cervical cancer. Women with rheumatic conditions are immunosuppressed due to the disease and the treatments. One of the main risk factors for this neoplasm is the lack of adherence to early detection programmes for human papillomavirus. The objectives of this study were to evaluate the adherence to the screening programme of patients in the Rheumatology Clinic, as well as to evaluate the prevalence of cervical lesions and their association with the different disease characteristics and the treatments received. METHODS: A descriptive retrospective study. The electronic medical history of patients actively being followed up in a tertiary hospital with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and systemic lupus erythematosus (SLE) were reviewed. RESULTS: Finally, 307 patients were included. No data were found for screening programme attendance in up to 42.4% of the patients (39.6% in RA, 43.8% in PSA and 46% in SLE). Among the patients who attended the screening programme at least once (57.6%), the prevalence of cervical dysplasia was 5.1%. No cases of neoplasia were found. In the simple logistic regression analysis, there was no association between attending the screening programme and any variable. The study also showed no association between the variables collected and the presence of infection and dysplasia. CONCLUSION: These results are influenced by the absence of screening data in a significant percentage of patients and by the low prevalence of dysplasia found in this series of patients with rheumatic diseases.

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.

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.

Human Papiloma Virus Screening: Evaluation Of Testing And Surveillance In Rheumatoid Arthritis, Psoriatic Arthritis And Systemic Lupus Erythematosus. / Cribado del virus de papiloma humano: evaluación de grado de vigilancia en artritis reumatoide, artritis psoriásica y lupus eritematoso sistémico.

BACKGROUND AND OBJECTIVES: Immunosuppression is a known risk factor for cervical cancer. Women with rheumatic conditions are immunosuppressed due to the disease and the treatments. One of the main risk factors for this neoplasm is the lack of adherence to early detection programmes for human papillomavirus. The objectives of this study were to evaluate the adherence to the screening programme of patients in the Rheumatology Clinic, as well as to evaluate the prevalence of cervical lesions and their association with the different disease characteristics and the treatments received. MATERIAL AND METHODS: A descriptive retrospective study. The electronic medical history of patients actively being followed up in a tertiary hospital with rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus were reviewed. RESULTS: Finally, 307 patients were included. No data were found for screening programme attendance in up to 42.4% of the patients (39.6% in rheumatoid arthritis, 43.8% in psoriatic arthritis and 46% in systemic lupus erythematosus). Among the patients who attended the screening programme at least once (57.6%), the prevalence of cervical dysplasia was 5.1%. No cases of neoplasia were found. In the simple logistic regression analysis, there was no association between attending the screening programme and any variable. The study also showed no association between the variables collected and the presence of infection and dysplasia. CONCLUSION: These results are influenced by the absence of screening data in a significant percentage of patients and by the low prevalence of dysplasia found in this series of patients with rheumatic diseases.

Role of Carotid Ultrasound and Systematic Coronary Risk Evaluation Charts for the Cardiovascular Risk Stratification of Patients with Psoriatic Arthritis.

OBJECTIVE: The assessment of the cardiovascular (CV) risk is recommended in patients with chronic inflammatory rheumatic diseases. The objectives of this study were to assess the CV risk profile in a cohort of patients with psoriatic arthritis (PsA), to determine the presence of subclinical cardiovascular disease by carotid ultrasound (US), and to study the association of CV disease to PsA characteristics. METHODS: This was a cross-sectional multicentric descriptive study. The clinical CV risk was calculated with Systematic Coronary Risk Evaluation (SCORE) charts. Common carotid US was conducted to evaluate the carotid wall intima-media thickness and the presence of atheroma plaques. Patients were reclassified upon US results. Multivariate analyses were performed to identify associations of US carotid abnormalities with the classical CV risk factors and PsA characteristics. RESULTS: The study included 176 patients with PsA. The SCORE-estimated CV risk was intermediate in 65.3% of the patients. In the US study, 32% of the patients had abnormalities, and 30.8% of the patients were upgraded and reclassified as very high risk owing to the presence of atheroma. Subclinical CV disease was associated with age and dyslipidemia but not with other risk factors. It was associated with axial disease in the subgroup with intermediate risk, and with C-reactive protein levels in patients with high risk. CONCLUSION: Many patients with PsA have clinical estimated intermediate or high risk of a fatal CV event. A carotid US study detects subclinical vascular disease and may be useful to depict the real risk. The presence of atheroma is only partially explained by the classic CV risk factors.

Omentin: a biomarker of cardiovascular risk in individuals with axial spondyloarthritis.

Cardiovascular (CV) disease is the main cause of mortality in axial spondyloarthritis (axSpA). CV risk is enhanced by dysregulation of adipokines. Low omentin levels were associated with metabolic dysfunction and CV disease in conditions different from axSpA. Accordingly, we evaluated the genetic and functional implication of omentin in CV risk and subclinical atherosclerosis in a cohort of 385 axSpA patients. Subclinical atherosclerosis was evaluated by carotid ultrasound. Omentin rs12409609, in linkage disequilibrium with a polymorphism associated with CV risk, was genotyped in 385 patients and 84 controls. Serum omentin levels were also determined. omentin mRNA expression was assessed in a subgroup of individuals. Serum and mRNA omentin levels were lower in axSpA compared to controls. Low serum omentin levels were related to male sex, obesity, inflammatory bowel disease (IBD) and high atherogenic index. rs12409609 minor allele was associated with low omentin mRNA expression in axSpA. No association was observed with subclinical atherosclerosis at the genetic or functional level. In conclusion, in our study low omentin serum levels were associated with CV risk factors in axSpA. Furthermore, rs12409609 minor allele may be downregulating the expression of omentin. These data support a role of omentin as a CV risk biomarker in axSpA.

Spanish Registry of Recent-onset Psoriatic Arthritis (REAPSER study): Aims and methodology. / Registro Español de Artritis Psoriásica de Reciente Comienzo (estudio REAPSER). Objetivos y metodología.

AIMS: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2years of symptom evolution. METHODS: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. CONCLUSIONS: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis.

Is the SCORE chart underestimating the real cardiovascular (CV) risk of patients with psoriatic arthritis? Prevalence of subclinical CV disease detected by carotid ultrasound.

OBJECTIVES: To analyse the cardiovascular risk according to the SCORE chart in a series of patients with psoriatic arthritis, and to study the presence of subclinical cardiovascular disease by carotid ultrasound. METHODS: Cross-sectional descriptive study of patients with psoriatic arthritis attended in a tertiary hospital. The presence of classical cardiovascular risk factors and the clinical characteristics of the patients were recorded. The cardiovascular risk was calculated with SCORE, calibrated for Spain. Common carotid ultrasound was conducted to assess intima-media thickness and the presence of atheroma plaques. Patients were reclassified upon ultrasound results. Statistical analyses were made for sample description, and multivariate analyses were performed to investigate the associations with the presence of atheroma plaques. RESULTS: A total of 102 patients were included. According to SCORE charts, 70.6% of the patients had intermediate cardiovascular risk, 25.5% high risk and 3.9% very high risk. After the ultrasound study, 26.5% of the patients were upgraded, and reclassified as very high risk due to the presence of plaques. The presence of subclinical vascular disease was associated with higher uric acid levels (P=0.036) and the presence of 2 or more cardiovascular risk factors (P=0.021). CONCLUSIONS: A considerable number of psoriatic arthritis patients have a priori moderate or high risk of a fatal cardiovascular event. Carotid ultrasound detects subclinical vascular disease and increases the real risk in a substantial proportion of patients. Cardiovascular risk prediction clinical tools such as the SCORE underestimate the presence of subclinical cardiovascular disease in patients with psoriatic arthritis.

Use of benzodiazepines and antidepressants in patients who attend a Rheumatology clinic / Prevalencia de consumo de benzodiacepinas y antidepresivos en los pacientes que acuden por primera vez a la consulta de reumatología

ABSTRACT Introduction: During the last decades, benzodiazepines (BZD) and antidepressants (ADP) have been among the most prescribed therapies in all developed countries. They have side effects, and BZD carry a risk of abuse and dependence disorders. The purpose of this study was to evaluate the prevalence of BZD and ADP among patients who attend a Rheumatology clinic, as well as the indication for these drugs. Methods: The study included patients who were referred for the first time to the Rheumatology clinic. Demographical data, reason for referral, and final diagnosis were recorded. The indication for ADP and/or BZD was recorded, as well as the duration of treatment. Sample size was estimated for a 0.05% alpha risk. Univariate and multivariate analyses were performed in order to study the relationships with the demographical or clinical characteristics. Results: A total of 350 patients were included (women 77.1%, men 22.9%). Most of them (73.4%) had been referred for musculoskeletal pain. More than a third (36.6%) of patients were on BZD and/or ADP. The most frequent reasons for their prescription were anxiety, depression, and insomnia. The final diagnosis in the clinic was a non-inflammatory condition in 82%, and an inflammatory one in 18%. In the univariate analyses, the use of BZD/ADP was associated with female gender (p<.001), unemployment (p<.001) and non-inflammatory final diagnosis (p < .001). In the multivariate analyses, the use of BZD and/or ADP was associated with female sex (p = .002 [OR 3.4, 95% CI; 1.6-7.4]), and a non-inflammatory final diagnosis, specifically fibromyalgia (p = .007 [OR 16.1, 95% CI; 2.2-120.7]). Conclusion: Use of BZD and ADP is high and associated with non-inflammatory disease.

RESUMEN Introducción: Durante las últimas décadas, las benzodiacepinas (BZD) y los antidepresivos (ADP) han estado entre las terapias más prescritas en todos los países desarrollados. Estos fármacos tienen efectos secundarios y las BZD pueden ocasionar abuso y problemas de dependencia. El objetivo de este estudio fue evaluar la prevalencia de consumo de BZD y ADP entre los pacientes que acuden a una consulta de reumatología por primera vez, así como la indicación para ellos. Métodos: Se incluyeron pacientes remitidos por primera vez a la consulta de reumatología. Se registraron los datos demográficos, el motivo de la derivación y el diagnóstico final. Con respecto al tratamiento con ADP y/o BZD, se registraron su duración y la indicación de la prescripción. El tamaño de la muestra se estimó para un riesgo alfa de 0,05%. Se realizaron análisis univariantes y multivariantes para estudiar las asociaciones con características demográficas o clínicas. Resultados: Se incluyeron 350 pacientes (mujeres 77,1%, hombres 22,9%). La mayoría de ellos habían sido remitidos por dolor musculoesquelético (73,4%). Más de un tercio (36,6%) de los pacientes estaban en tratamiento con BZD y/o ADP. Las causas más frecuentes para su prescripción fueron ansiedad, depresión e insomnio. El diagnóstico final fue patología no inflamatoria en el 82% de los casos e inflamatoria en el 18% de estos. En el análisis univariante, el uso de BZD y/o ADP se asoció con el sexo femenino (p< 0,001), el desempleo (p< 0,001) y el diagnóstico de patología no inflamatoria (p< 0,001). En el análisis multivariante, el uso de BZD y/o ADP se asoció con el sexo femenino (p=0,002 [OR 3,4; IC 95% 1,6-7,4]) y el diagnóstico de patología no inflamatoria, específicamente con la fibromyalgia (p = 0,007 [OR 16,1; IC 95% 2,2-120,7]). Conclusión: El consumo de BZD y ADP es frecuente y está asociado con patología no inflamatoria.