Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study.

Objective: To describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients and methods: The study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection. Results: We followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants. Conclusion: Patients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care.

Impact of multimorbidity on the first ts/bDMARD effectiveness and retention rate after two years of follow-up in patients with rheumatoid arthritis from the BIOBADASER registry.

BACKGROUND: Patients with Rheumatoid Arthritis (RA) have a higher prevalence of comorbidities compared to the general population. However, the implications of multimorbidity on therapeutic response and treatment retention remain unexplored. OBJECTIVES: (a) To evaluate the impact of multimorbidity on the effectiveness of the first targeted synthetic or biologic disease-modifying antirheumatic drug (ts/bDMARD), in patients with RA after 2-year follow-up; (b) to investigate the influence of multimorbidity on treatment retention rate. METHODS: Patients with RA from the BIOBADASER registry exposed to a first ts/bDMARDs were included. Patients were categorized based on multimorbidity status at baseline, defined as a Charlson Comorbidity index (CCI) score ≥ 3. A linear regression model, adjusted for sex and age, was employed to compare the absolute DAS28 score over time after ts/bDMARD initiation between the two groups. The Log-Rank test and Kaplan-Meier curve were used to compare the retention rates of the first ts/bDMARD between the groups. RESULTS: A total of 1128 patients initiating ts/bDMARD were included, with 107 (9.3%) exhibiting multimorbidity. The linear regression model showed significantly higher DAS28 (beta coefficient 0.33, 95%CI:0.07-0.58) over a two-year period in patients with multimorbidity, even after adjusting for age and sex. Finally, no differences in the ts/bDMARD retention rate were found between groups (median 6.94-6.96 years in CCI < 3 vs. 5.68-5.62 in CCI ≥ 3; p = 0.610). CONCLUSIONS: Multimorbidity in patients with RA was associated with greater DAS28 scores within the first two years after ts/bDMARD initiation, in comparison with patients without multimorbidity. A slightly shorter retention rate was found in patients with multimorbidity, although the difference was non-significant.

Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study.

OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (

Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling.

Introduction: RA patients are at higher risk of cardiovascular disease, influenced by therapies. Studying their cardiovascular and cardiometabolic proteome can unveil biomarkers and insights into related biological pathways. Methods: This study included two cohorts of RA patients: newly diagnosed individuals (n=25) and those with established RA (disease duration >25 years, n=25). Both cohorts were age and sex-matched with a control group (n=25). Additionally, a longitudinal investigation was conducted on a cohort of 25 RA patients treated with methotrexate and another cohort of 25 RA patients treated with tofacitinib for 6 months. Clinical and analytical variables were recorded, and serum profiling of 184 proteins was performed using the Olink technology platform. Results: RA patients exhibited elevated levels of 75 proteins that might be associated with cardiovascular disease. In addition, 24 proteins were increased in RA patients with established disease. Twenty proteins were commonly altered in both cohorts of RA patients. Among these, elevated levels of CTSL1, SORT1, SAA4, TNFRSF10A, ST6GAL1 and CCL18 discriminated RA patients and HDs with high specificity and sensitivity. Methotrexate treatment significantly reduced the levels of 13 proteins, while tofacitinib therapy modulated the expression of 10 proteins. These reductions were associated with a decrease in DAS28. Baseline levels of SAA4 and high levels of BNP were associated to the non-response to methotrexate. Changes in IL6 levels were specifically linked to the response to methotrexate. Regarding tofacitinib, differences in baseline levels of LOX1 and CNDP1 were noted between non-responder and responder RA patients. In addition, response to tofacitinib correlated with changes in SAA4 and TIMD4 levels. Conclusion: In summary, this study pinpoints molecular changes linked to cardiovascular disease in RA and proposes candidate protein biomarkers for distinguishing RA patients from healthy individuals. It also highlights how methotrexate and tofacitinib impact these proteins, with distinct alterations corresponding to each drug's response, identifying potential candidates, as SAA4, for the response to these therapies.

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.

Analysis of comorbidity in rheumatoid arthritis-associated interstitial lung disease: a nested case-cohort study.

OBJECTIVES: To describe comorbid conditions in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity. METHODS: Nested case-cohort study of 2 prospective cohorts: one with RA-ILD (cases) and another with RA but not ILD (controls). The cohorts were matched for age, sex, and time since diagnosis. Multimorbidity was defined as the co-occurrence of 2 or more chronic diseases, in addition to RA and ILD. We evaluated the comorbid conditions included in the Charlson Comorbidity Index, cardiovascular risk factors, neuropsychiatric conditions, and other frequent conditions in RA. We also recorded clinical-laboratory variables, inflammatory activity according to the 28-joint Disease Activity Score, C-reactive protein (CRP), physical function, and pulmonary function. We performed 2 multivariate analyses to identify factors associated with multimorbidity in RA and RA-ILD. RESULTS: The final study population comprised 110 cases and 104 controls. Multimorbidity was more frequent among cases than controls (80 [72.7] vs 60 [57.7]; p = 0.021). In both groups, multimorbidity was associated with ILD (OR [95% CI] 1.92 [1.03-3.59]; p = 0.039), age (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004), CRP (OR [95% CI] 1.16 [1.05-1.29]; p = 0.003), and erosions (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004); in the cases, it was associated with CRP (OR [95% CI] 1.17 [1.01-1.35]; p = 0.027), anti-citrullinated peptide antibody (OR [95% CI] 1.23 [1.14-13.02]; p = 0.049), and forced vital capacity (OR [95% CI] 0.79 [0.96-0.99]; p = 0.036). CONCLUSION: In patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age.

Safety and Effectiveness of Abatacept in a Prospective Cohort of Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease.

OBJECTIVE: To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: We performed a prospective observational multicenter study of a cohort of patients with RA-ILD treated with abatacept between 2015 and 2021. Patients were evaluated using high-resolution computed tomography and pulmonary function tests at initiation, 12 months, and the end of follow-up. The effectiveness of abatacept was evaluated based on whether ILD improved, stabilized, progressed, or was fatal. We also evaluated factors such as infection, hospitalization, and inflammatory activity using the 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR). Cox regression analysis was performed to identify factors associated with progression of lung disease. RESULTS: The study population comprised 57 patients with RA-ILD treated with abatacept for a median (IQR) of 27.3 (12.2-42.8) months. Lung disease had progressed before starting abatacept in 45.6% of patients. At the end of follow-up, lung disease had improved or stabilized in 41 patients (71.9%) and worsened in 13 (22.8%); 3 patients (5.3%) died. No significant decreases were observed in forced vital capacity (FVC) or in the diffusing capacity of the lung for carbon monoxide (DLCO).The factors associated with progression of RA-ILD were baseline DAS28-ESR (OR [95% CI], 2.52 [1.03-3.12]; p = 0.041), FVC (OR [95% CI], 0.82 [0.70-0.96]; p = 0.019), and DLCO (OR [95% CI], 0.83 [0.72-0.96]; p = 0.018). Only 10.5% of patients experienced severe adverse effects. CONCLUSION: Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile.

Subclinical Atherosclerosis Measure by Carotid Ultrasound and Inflammatory Activity in Patients with Rheumatoid Arthritis and Spondylarthritis.

OBJECTIVE: To compare the effect of inflammation on subclinical atherosclerosis using carotid ultrasound in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: Cross-sectional study including 347 participants (148 RA, 159 SpA, and 40 controls). We measured the carotid intima media thickness (cIMT) and detection of atheromatous plaques using carotid ultrasound. We recorded disease activity (DAS28-CRP/ASDAS-CRP) and traditional cardiovascular risk factors. We performed descriptive, bivariate, and linear multivariate analyses (dependent variable: cIMT) to evaluate the influence of diagnosis on cIMT in all patients. Two additional multivariate analyses were performed by stratifying patients according to their inflammatory activity. RESULTS: cIMT correlated with the mean CRP during the previous 5 years in RA, but not with CRP at the cut-off date. We did not find such differences in patients with SpA. The first multivariate model revealed that increased cIMT was more common in patients with RA than in those with SpA (ß coefficient, 0.045; 95% confidence interval (95% CI), 0.0002-0.09; p = 0.048) after adjusting for age, sex, disease course, and differential cardiovascular risk factors (arterial hypertension, smoking, statins, and corticosteroids). The second model revealed no differences in cIMT between the 2 groups of patients classified as remission-low activity (ß coefficient, 0.020; 95% CI, -0.03 to 0.080; p = 0.500). However, when only patients with moderate-high disease activity were analysed, the cIMT was 0.112 mm greater in those with RA (95% CI, 0.013-0.212; p = 0.026) than in those with SpA after adjusting for the same variables. CONCLUSIONS: Subclinical atherosclerosis measured by carotid ultrasound in patients with RA and SpA is comparable when the disease is well controlled. However, when patients have moderate-high disease activity, cIMT is greater in patients with RA than in those with SpA after adjusting for age, sex, disease course, and cardiovascular risk factors. Our results point to greater involvement of disease activity in subclinical atherosclerosis in patients with RA than in those with SpA.

Molecular Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Disease-Modifying Anti-Rheumatic Drugs.

Disease severity, progression and response to therapy might be worse in obese rheumatoid arthritis (RA) patients, but paradoxically, obesity also might protect from radiographic joint damage. Thus, the intricate relationship between obesity and RA needs urgent clarification. The aim of this study was to assess the influence of obesity on the onset and development of RA and to determine whether arthritis could modify the adipose tissue biology and whether conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) can modulate these alterations. Two strategies were followed: (1) clinical profiling of two cohorts of RA: non-obese and obese patients; and (2) mechanistic studies carried out in both a collagen-induced arthritis (CIA) in an obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, and hydroxychloroquine). In our cohort of RA patients with low-moderate disease activity, the presence of obesity was not related to a higher activity of the disease; actually, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) was reduced in the obese RA patients. However, the induction of arthritis promoted transcriptomic changes in the adipose tissue under obesity condition in the obese CIA model. Treatment with hydroxychloroquine reduced weight and insulin resistance, accompanied by beneficial metabolic effects in the adipose tissue. These molecular changes in adipose tissue were also observed after methotrexate administration. In sum, arthritis might affect directly the inflammatory burden and metabolic alterations associated with obesity in adipose tissue. Clinicians should be cautious measuring the activity of the disease in obesity and managing the best therapeutic options for the metabolic comorbidities of these patients, where the combination of hydroxychloroquine and methotrexate should be considered to improve adipose tissue dysfunction in obese RA.

Genetic Polymorphisms of GGH and ABCC2 Are Associated with Methotrexate Intolerance in Patients with Rheumatoid Arthritis.

OBJECTIVE: to identify new single-nucleotide polymorphisms (SNPs) in genes encoding proteins involved in methotrexate (MTX) metabolism and to evaluate the associations of these SNPs with MTX toxicity or intolerance in a southern Spanish cohort of patients with rheumatoid arthritis (RA). METHODS: An observational, retrospective, and multicenter study was conducted at three participating hospitals in southern Spain. The main variable was intolerance to MTX (i.e., bDMARD monotherapy), defined as an interruption of treatment due to adverse events or toxicity. Patients being treated with MTX and bDMARDs (combined treatment) at the time of the study visit were considered "tolerant" of MTX. Ten polymorphisms were selected for sequencing in our patients according to a literature review. Each polymorphism was classified according to three possible genotypes (e.g., two homozygous (AA or GG) and one heterozygous (AG)), and the association of these combinations with MTX intolerance was evaluated. RESULTS: A total of 227 patients were included in the final analysis (107 intolerant of MTX and 120 tolerant). A significant association was observed between MTX intolerance and the GGH-T401C AA/AG genotype (OR 2.13, 95% CI 1.06-4.29) in comparison with the GG genotype. On the other hand, an inverse association was observed between the ABCC2-C24T TT/TC genotype and intolerance to MTX (OR 0.59, 95% CI 0.35-1.00) in comparison with the CC genotype. CONCLUSION: This study provides new data on the association between genetic polymorphisms and MTX intolerance, which may contribute to the development of new biomarkers and personalized medicine in patients with RA.

Association between Carotid Intima-Media Thickness and the Use of Biological or Small Molecule Therapies in Patients with Rheumatoid Arthritis.

OBJECTIVE: The objective of this study was to assess the association of carotid intima-media thickness (CIMT), and also the presence of atheromatous plaque, with biological and targeted synthetic disease-modifying antirheumatic drugs, in an established cohort of patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: We conducted a cross-sectional observational study based on a cohort of patients with RA and a registry of healthy controls, in whom the CIMT and presence of atheromatous plaque were assessed by ultrasound. Data were collected on disease activity, lab results and treatments. Descriptive and bivariate analyses were performed and two multivariate linear regression models (with CIMT as the dependent variable) were constructed to identify variables independently associated with CIMT in our sample of patients with RA. RESULTS: A total of 176 individuals (146 patients with RA and 30 controls) were included. A higher percentage of patients than controls had atheromatous plaque (33.8% vs. 12.5%, p = 0.036), but no differences were found in terms of CIMT (0.64 vs. 0.61, p = 0.444). Compared to values in patients on other therapies, the CIMT was smaller among patients on tumour necrosis factor alpha (TNFα) inhibitors (mean [SD]: 0.58 [0.10] vs. 0.65 [0.19]; p = 0.013) and among those on Janus kinase inhibitors (mean [SD]: 0.52 [0.02] vs. 0.64 [0.18]; p < 0.001), while no differences were found as a function of the use of the other therapies considered. The multivariate linear regression analysis to identify factors associated with CIMT in our patients, adjusting for traditional cardiovascular risk factors such as hypertension, high levels of low-density lipoproteins, diabetes mellitus and smoking, showed that male sex, older age and having a greater cumulative erythrocyte sedimentation rate were independently associated with a larger CIMT, while patients on TNFα inhibitors had a CIMT 0.075 mm smaller than those on other treatments. CONCLUSIONS: The use of TNFα inhibitors may protect against subclinical atherosclerosis in patients with RA, patients on this biologic having smaller CIMTs than patients on other disease-modifying antirheumatic drugs. Nonetheless, these results should be confirmed in prospective studies with larger sample sizes.

Impaired microRNA processing in neutrophils from rheumatoid arthritis patients confers their pathogenic profile. Modulation by biological therapies.

The aim of this study was to investigate the microRNA (miRNA) expression pattern in neutrophils from rheumatoid arthritis (RA) patients and its contribution to their pathogenic profile and to analyze the effect of specific autoantibodies or inflammatory components in the regulation of miRNA in RA neutrophils and its modulation by biological therapies. Neutrophils were isolated from paired peripheral blood (PB) and synovial fluid samples of 40 patients with RA and from PB of 40 healthy donors. A miRNA array was performed using nCounter technology. Neutrophils from healthy donors were treated in vitrowith antibodies to citrullinated protein antigens isolated from RA patients and tumor necrosis factor-a (TNF-a) or interleukin-6. A number of cytokines and chemokines were analyzed. In vitro treatments of RA-neutrophils with tocilizumab or infliximab were carried out. Transfections with pre-miRNA and DICER downregulation experiments were further performed. RA-neutrophils showed a global downregulation of miRNA and genes involved in their biogenesis, alongside with an upregulation of various potential mRNA targets related to migration and inflammation. Decreased levels of miRNA and DICER correlated with autoimmunity, inflammation and disease activity. Citrullinated protein antigens and TNF-a decreased the expression of numerous miRNA and their biogenesis-related genes, increasing their potential mRNA targets. Infliximab reversed those effects. Transfections with pre-miRNA-223, -126 and -148a specifically modulated genes regulating inflammation, survival and migration whereas DICER depletion influenced the inflammatory profile of neutrophils. Taken together RA-neutrophils exhibited a global low abundance of miRNA induced by autoantibodies and inflammatory markers, which potentially contributed to their pathogenic activation. miRNA biogenesis was significantly impaired in RAneutrophils and further associated with a greater downregulation of miRNA mainly related to migration and inflammation in synovial fluid neutrophils. Finally, anti-TNF-a and anti-interleukin-6 receptor treatments can modulate miRNA levels in the neutrophils, minimizing their inflammatory profile.

Complement component 3 as biomarker of disease activity and cardiometabolic risk factor in rheumatoid arthritis and spondyloarthritis.

OBJECTIVE: To analyze the relationship between complement component 3 (C3) and the prevalence of cardiometabolic risk factors and disease activity in the rheumatic diseases having the highest rates of cardiovascular morbidity and mortality: rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: This is a cross-sectional study including 200 RA, 80 PsA, 150 axSpA patients and 100 healthy donors. The prevalence of cardiometabolic risk factors [obesity, insulin resistance, type 2 diabetes mellitus, hyperlipidemia, apolipoprotein B/apolipoprotein A (apoB/apoA) and atherogenic risks and hypertension] was analyzed. Serum complement C3 levels, inflammatory markers and disease activity were evaluated. Cluster analysis was performed to identify different phenotypes. Receiver operating characteristic (ROC) curve analysis to assess the accuracy of complement C3 as biomarker of insulin resistance and disease activity was carried out. RESULTS: Levels of complement C3, significantly elevated in RA, axSpA and PsA patients, were associated with the prevalence of cardiometabolic risk factors. Hard clustering analysis identified two distinctive phenotypes of patients depending on the complement C3 levels and insulin sensitivity state. Patients from cluster 1, characterized by high levels of complement C3 displayed increased prevalence of cardiometabolic risk factors and high disease activity. ROC curve analysis showed that non-obesity related complement C3 levels allowed to identify insulin resistant patients. CONCLUSIONS: Complement C3 is associated with the concomitant increased prevalence of cardiometabolic risk factors in rheumatoid arthritis and spondyloarthritis. Thus, complement C3 should be considered a useful marker of insulin resistance and disease activity in these rheumatic disorders.

Molecular Characterization of Monocyte Subsets Reveals Specific and Distinctive Molecular Signatures Associated With Cardiovascular Disease in Rheumatoid Arthritis.

Objectives: This study, developed within the Innovative Medicines Initiative Joint Undertaking project PRECISESADS framework, aimed at functionally characterize the monocyte subsets in RA patients, and analyze their involvement in the increased CV risk associated with RA. Methods: The frequencies of monocyte subpopulations in the peripheral blood of 140 RA patients and 145 healthy donors (HDs) included in the PRECISESADS study were determined by flow cytometry. A second cohort of 50 RA patients and 30 HDs was included, of which CD14+ and CD16+ monocyte subpopulations were isolated using immuno-magnetic selection. Their transcriptomic profiles (mRNA and microRNA), proinflammatory patterns and activated pathways were evaluated and related to clinical features and CV risk. Mechanistic in vitro analyses were further performed. Results: CD14++CD16+ intermediate monocytes were extended in both cohorts of RA patients. Their increased frequency was associated with the positivity for autoantibodies, disease duration, inflammation, endothelial dysfunction and the presence of atheroma plaques, as well as with the CV risk score. CD14+ and CD16+ monocyte subsets showed distinctive and specific mRNA and microRNA profiles, along with specific intracellular signaling activation, indicating different functionalities. Moreover, that specific molecular profiles were interrelated and associated to atherosclerosis development and increased CV risk in RA patients. In vitro, RA serum promoted differentiation of CD14+CD16- to CD14++CD16+ monocytes. Co-culture with RA-isolated monocyte subsets induced differential activation of endothelial cells. Conclusions: Our overall data suggest that the generation of inflammatory monocytes is associated to the autoimmune/inflammatory response that mediates RA. These monocyte subsets, -which display specific and distinctive molecular signatures- might promote endothelial dysfunction and in turn, the progression of atherosclerosis through a finely regulated process driving CVD development in RA.

Evaluation of quality of life in patients with axial spondyloarthritis and its association with disease activity, functionality, mobility, and structural damage.

To evaluate quality of life (QoL) in patients with axial spondyloarthritis (axSpA) and its association with disease activity, functionality, structural damage, and spinal mobility, using patient-reported outcomes. This was an observational, cross-sectional, and single-center study in which 100 consecutive patients with axSpA were included. We obtained from all patients' sociodemographic data and values related to disease activity, functionality, structural damage, mobility, and quality of life. The Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) was considered as the primary outcome. Pearson r statistic, Student's T test, and univariate and multivariate linear regressions were performed to relate ASQoL with the studied covariates. Mean ASQoL score in all patients was 4.02 ± 2.81, with statistically significant differences between male and female (3.61 ± 2.80 vs. 4.83 ± 2.70). Patients with high disease activity (measured by the ASAS-endorsed Disease Activity Score, ASDAS > 2.1) showed higher mean score in ASQoL than those with low disease activity (ASDAS ≤ 2.1) (3.21 ± 0.74 vs. 1.43 ± 0.43, p < 0.001). ASQoL presented a significant linear correlation with BASDAI, BASFI, and ASDAS (r > 0.60). However, disease duration was not significantly correlated with ASQoL. Finally, the 68.9% of the ASQoL variability (R2 = 0.689) was determined by BASDAI, BASFI, and mSASSS, presenting mSASSS a negative regression coefficient (- 0.035). In our study, the impairment of QoL was mainly associated with disease activity (BASDAI) and worsening of functionality (BASFI). However, there is an inverse relationship between the worsening of QoL and structural damage. In addition, disease duration does not seem to influence the patient's welfare.

Cardiovascular risk factors in patients with spondyloarthritis from Northern European and Mediterranean countries: An ancillary study of the ASAS-COMOSPA project.

OBJECTIVES: The objectives of this study were: (1) to compare the prevalence of cardiovascular disease and cardiovascular risk factors among different phenotypes of spondyloarthritis (SpA); (2) to assess the differences in cardiovascular disease and cardiovascular risk factors between two geographical areas, i.e. Northern Europe vs. Mediterranean region; (3) to identify potential predictive factors for high Framingham Risk Score regarding disease features in SpA and geographical area. METHODS: Ancillary analysis of the international, multicentric, observational, cross-sectional ASAS-COMOSPA study. Cardiovascular disease and cardiovascular risk factors were compared depending on SpA phenotype and geographical regions. Potential factors associated with higher cardiovascular risk (i.e. Framingham Risk Score) were determined by a multiple logistic regression. RESULTS: The most frequent cardiovascular risk factor and cardiovascular disease were smoking (31.2%) and ischemic heart disease (3.2%), respectively. Regarding SpA phenotype, axial SpA patients showed significantly lower prevalence (P<0.05) of hypertension (19.2% vs. 33.8% vs. 26.6% for axial, peripheral and mixed phenotypes, respectively), type 2 diabetes mellitus (4.3% vs. 8.5% vs. 7.4%), dyslipidemia (13.9% vs. 28.4% vs. 15.2%) and ischemic heart disease (2.4% vs. 7.0% vs. 3.2%). Regarding geographical area, a higher frequency of hypertension (34.7% vs. 19.4%,), dyslipidemia (19.3% vs. 14.4%), obesity (29.3% vs. 20.7%) and ischemic heart disease (6.2% vs. 1.8%) was observed for Northern Europe vs. Mediterranean Region, respectively. CONCLUSIONS: Our results suggest that SpA phenotype and geographical area are associated with the prevalence of cardiovascular risk factors and the cardiovascular risk itself, observed in patients in the ASAS-COMOSPA cohort.

Optimization of biological therapy in rheumatoid arthritis patients: outcomes from the CREATE registry after 2 years of follow-up.

The current strategy for managing rheumatoid arthritis (RA) focuses on achieving clinical remission. Once remission is achieved and sustained over time, the most efficient strategy is dose optimization. This work describes the results of dose optimization after 2 years of follow-up in patients with RA treated with biological therapy and identifies predictive variables of response. Cohort: patients from the CREATE registry who, as of 1 November 2013, had been in clinical remission (DAS28 ≤2.6) for at least 6 months. INTERVENTION: Dose optimization was 20-50% of the standard dose. Outcome measurement were effectiveness (percentage of patients who continued to meet criteria for clinical remission) and efficiency (dose reduction and mean savings). Sixty-eight patients with RA were optimized, with initial mean DAS28 of 2.2 ± 0.7. After 2 years of follow-up, the mean DAS28 was 2.4 ± 0.7, a non-statistically significant difference. Twenty-eight patients (41.2%) continued in clinical remission with dose optimization after 2 years. Mean survival time was 14.2 months (95% CI 12.0-16.5). Of the 40 patients who needed to return to a standard dose, 57.5% managed to achieve remission again at 2 years. Mean dose reduction at 2 years was 21.17%, reaching a mean saving of €5576 ± 5099 per patient. In actual clinical practice, over 40% of patients with established RA who had been in sustained clinical remission managed to continue in remission 2 years after receiving optimized doses. The savings achieved was about 21% of the actual direct health costs for patients in the CREATE registry.

Assessment of Fatigue in Spondyloarthritis and Its Association with Disease Activity.

OBJECTIVE: To evaluate fatigue in patients with spondyloarthritis (SpA) and to define its association with disease-related factors and patients' features. METHODS: A cross-sectional multicenter study which includes 2251 patients with SpA selected from the national Spondyloarthropathies Registry (the Spanish Society of Rheumatology; REGISPONSER) Spanish cohort. The primary outcome was the assessment of fatigue performed with the first item of the Bath Ankylosing Spondyloarthritis Disease Activity Index followed by the study of its relation with different factors organized into 4 groups: sociodemographics, emotional, disease-related, and disease activity. Univariate logistic regressions, multivariate logistic regression, and multiple linear regressions were performed to relate fatigue with the studied covariates. RESULTS: Mean fatigue score in all patients with SpA was 4.3 ± 2.9, with statistically significant differences between different SpA types. In univariate logistic regressions, significant differences were seen for many variables included in the 4 groups. Multivariate logistic regression showed that high fatigue score was related with sex (female), emotional component, the Ankylosing Spondylitis Quality of Life score, stiffness, and high levels of 2 visual analog scale items (vertebral pain in the last week and patient's global assessment of disease activity). The multivariate linear regression showed that fatigue was mainly explained by disease-related factors and disease activity (54.1%), but sex and emotional status may also be involved in 13.5% of the variance. CONCLUSION: Fatigue is associated with disease-related factors and mostly with SpA activity. However, the emotional component and sex may contribute to the onset of fatigue.

Is spinal mobility in patients with spondylitis determined by age, structural damage, and inflammation?

OBJECTIVE: To explore the association between mobility, inflammation, and structural damage in ankylosing spondylitis (AS). METHODS: Patients with AS were included in a cross-sectional study in which spinal mobility was measured by the Bath Ankylosing Spondylitis Metrology Index (BASMI) and by the University of Córdoba Ankylosing Spondylitis Metrology Index (UCOASMI), based on an automated motion analysis. Structural damage was measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), and activity by the Ankylosing Spondylitis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity (BASDAI). We analyzed the correlations between variables, as well as interaction by multiple linear regression models to reach a predictive equation. RESULTS: Fifty AS patients, mainly men in their mid-40s and with moderate levels of disease activity and structural damage, were included in the study. BASMI and UCOASMI scores showed a strong correlation (r = 0.89). UCOASMI scores correlated stronger than BASMI with structural damage (r = 0.72 versus r = 0.67) and patient's age (r = 0.68 versus r = 0.56). Correlations of mobility were weaker with disease activity by the ASDAS (r = 0.38) and BASDAI (r = 0.49), and disease duration (r = 0.40). Multiple linear regression showed that factors associated to mobility by UCOASMI were age, the BASDAI, mSASSS, ASDAS (0:<2.1, 1:≥2.1), and disease duration >15 years. The largest weight in the equation corresponded to the mSASSS. The association between the ASDAS and UCOASMI is dependent on disease duration. CONCLUSION: Mobility in AS is influenced by both structural damage and activity, but definitely also by age and disease duration. Improved mobility should be a relevant target in AS, even more prominently than activity, given its closer relation to structural damage.