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Background: Few studies have been conducted to investigate the socioeconomic profiles of patients with ankylosing spondylitis (AS) and their associations with disease severity and disability. Objectives: The objectives of this study were to identify clusters of patients with AS according to their socioeconomic characteristics and to evaluate the associations between these clusters and the severity of the disease and permanent disability. Design: This was a cross-sectional and multicentre study. Methods: Patients with AS from the REGISPONSER study were included in this analysis. A cluster analysis was conducted using information on sociodemographic (age, sex, race, marital status, education) and socioeconomic (employment, profession, housing conditions and social level) characteristics. Disease burden and permanent disability were compared between the different clusters using logistic regression adjusted for disease duration and disease activity. Results: A total of 866 patients with AS were included. Two clusters were identified according to socioeconomic characteristics: Cluster 1 ( n = 476), with a predominantly low socioeconomic profile, and Cluster 2 ( n = 390), with a predominantly high socioeconomic profile. After adjusting for disease duration, patients in Cluster 1 had a longer diagnosis delay, greater body mass index and greater structural damage than those in Cluster 2. Access to biologic disease-modifying anti-rheumatic drugs (bDMARDs) was similar for both groups. However, patients in Cluster 1 had a greater prevalence of permanent disability than those in Cluster 2 after adjusting for disease duration and disease activity (30.8% vs 13.2%, odds ratio 2.58 (95% confidence interval 1.76–3.83)). Conclusion: This study suggests that the socioeconomic status of patients with AS may have implications for disease severity and permanent disability, despite the similar use of bDMARDs.

Psoriatic disease, encompassing both psoriasis (Pso) and psoriatic arthritis (PsA), is closely intertwined with a significantly elevated risk of developing cardiovascular diseases. This connection is further compounded by a higher prevalence of cardiometabolic comorbidities, including type 2 diabetes, obesity, insulin resistance, arterial hypertension, and dysregulated lipid profiles. These comorbidities exceed the rates seen in the general population and compound the potential for increased mortality among those living with this condition. Recognizing the heightened cardiometabolic risk inherent in psoriatic disease necessitates a fundamental shift in the treatment paradigm. It is no longer sufficient to focus solely on mitigating inflammation. Instead, there is an urgent need to address and effectively manage the metabolic parameters that have a substantial impact on cardiovascular health. Within this context, apremilast emerges as a pivotal treatment option for psoriatic disease. What sets apremilast apart is its dual-action potential, addressing not only inflammation but also the critical metabolic parameters. This comprehensive treatment approach opens up new opportunities to improve the well-being of people living with psoriatic disease. This review delves into the multifaceted aspects involved in the development of cardiovascular disease and its intricate association with psoriatic disease. We then provide an in-depth exploration of the pleiotropic effects of apremilast, highlighting its potential to simultaneously mitigate metabolic complications and inflammation in individuals affected by these conditions.

Abstract 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

Objective To evaluate the sensitivity to change in structural imaging outcomes over 10 years of follow-up in patients with axial spondyloarthritis (axSpA).Methods Patients with axSpA from the Devenir des Spondyloarthropathies Indifferénciées Récentes cohort were included. Radiographs and MRIs of the sacroiliac joints (SIJ) and spine were obtained at baseline and at 1, 2, 5 and 10 years. The yearly rate of change of each structural outcome was analysed using generalised estimating equation models, including all patients with ≥1 score from ≥1 reader from ≥1 reading wave, using the time (years) as an explanatory variable and adjusting for reader and wave. All outcomes were standardised, and the relative standardised rate of change was calculated (ie, the standardised rate of an outcome divided by the rate of a reference outcome).Results A total of 659 patients (46% males and mean age 33.6 years) were included. The most sensitive outcome to change in the SIJ (both MRI and radiographs) was the presence of ≥3 fatty lesions at a specific timepoint, with a relative standardised rate of change per year of 5.28 using the modified New York criteria as reference.Similarly, the most sensitive to change (in both MRI and radiographs) outcome in the spine was the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; relative standardised yearly change 1.76) using ≥1 syndesmophyte as reference.Conclusion MRI structural outcomes in the SIJ (ie, fatty lesions) are more sensitive to change than radiographic outcomes. Conversely, the mSASSS remains the most sensitive method, even when compared with MRI of the spine.

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 (β 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 (β 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.

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:

IntroductionAxial spondyloarthritis (axSpA) is a heterogeneous disease that can be represented by radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). This study aimed to evaluate the relationship between the markers of inflammation and bone turnover in r-axSpA patients and nr-axSpA patients.MethodsA cross-sectional study included 29 r-axSpA patients, 10 nr-axSpA patients, and 20 controls matched for age and sex. Plasma markers related to bone remodeling such as human procollagen type 1 N-terminal propeptide (P1NP), sclerostin, tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were measured by an ELISA kit. A panel of 92 inflammatory molecules was analyzed by proximity extension assay.ResultsR-axSpA patients had decreased plasma levels of P1NP, a marker of bone formation, compared to controls. In addition, r-axSpA patients exhibited decreased plasma levels of sclerostin, an anti-anabolic bone hormone, which would not explain the co-existence of decreased plasma P1NP concentration; however, sclerostin levels could also be influenced by inflammatory processes. Plasma markers of osteoclast activity were similar in all groups. Regarding inflammation-related molecules, nr-axSpA patients showed increased levels of serum interleukin 13 (IL13) as compared with both r-axSpA patients and controls, which may participate in the prevention of inflammation. On the other hand, r-axSpA patients had higher levels of pro-inflammatory molecules compared to controls (i.e., IL6, Oncostatin M, and TNF receptor superfamily member 9). Correlation analysis showed that sclerostin was inversely associated with IL6 and Oncostatin M among others.ConclusionAltogether, different inflammatory profiles may play a role in the development of the skeletal features in axSpA patients particularly related to decreased bone formation. The relationship between sclerostin and inflammation and the protective actions of IL13 could be of relevance in the axSpA pathology, which is a topic for further investigation.

IntroductionRA 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.MethodsThis 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. ResultsRA 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. ConclusionIn 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.

Objectives To describe and compare the prevalence of comorbidities in female and male patients with spondyloarthritis (SpA) and to assess whether comorbidities had a different impact on disease outcomes in male and female patients.Methods This is a post hoc analysis of the COMOrbidities in SPondyloArthritis study. Differences in comorbidities regarding sex were assessed using logistic regression models. Comorbidities were evaluated for their impact on disease outcomes (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index, European health-related quality of life questionnaire) with linear models, which included sex and comorbidity as explanatory variables and their interaction. Age and treatment with biological synthetic disease-modifying antirheumatic drugs were included as confounders.Results We included 3982 patients with SpA (65% male, mean age 43.6 years). Male and female patients with SpA exhibited similar comorbidity profiles, except for a low prevalence of fibromyalgia in males and a higher prevalence of certain cardiovascular risk factors in males (hypertension, dyslipidaemia, renal impairment and ischaemic heart disease). Comorbidities, especially fibromyalgia, correlated with higher disease activity, decreased physical function and reduced health-related quality of life in both sexes. Some comorbidities exhibited sex-specific associations with disease outcomes. Peptic ulcers and high waist circumference had a greater impact on disease activity in females (with a higher impact in BASDAI than in ASDAS). In contrast, osteoporosis had a more pronounced effect on physical function in male patients.Conclusions Comorbidities exert distinct influences on disease activity, physical function and health-related quality of life in male and female patients with SpA. Understanding these sex-specific effects is crucial for improving SpA management, emphasising the importance of assessing disease activity using ASDAS when comorbidities are present to mitigate sex-related disparities in disease assessment.

Abstract Background In axial spondyloarthritis (axSpA), peripheral SpA (pSpA) and psoriatic arthritis (PsA), enthesitis is a hallmark clinical feature that can be assessed by the SPARCC index, LEI, MASES and MEI. These indices evaluate different locations, which may identify different numbers of patients with enthesitis among SpA subtypes. Thus, the aim of this study was to evaluate whether the proportion of patients with at least one enthesitis across these three most prevalent SpA subtypes differs according to the index used and to evaluate the level of agreement among indices in detecting patients with enthesitis. Methods A total of 4185 patients (2719 axSpA, 433 pSpA and 1033 PsA) from the international and cross-sectional ASAS-PerSpA study were included. The proportion of patients with enthesitis identified by the indices was evaluated across the three diseases. Pairwise agreement between indices was computed using Cohen’s kappa. Results The prevalence rates of patients with at least one enthesitis according to the MEI, MASES, SPARCC index and LEI were 17.2%, 13.5%, 10.7%, and 8.3%, respectively. In axSpA, the indices that identified the most patients with enthesitis were the MEI and MASES (98.7% and 82.4%, respectively); in pSpA and PsA, the indices that identified the most patients with enthesitis were the MEI and SPARCC index (MEI: 100% and SPARCC: 84.6%; MEI: 97.3% and SPARCC: 77%, respectively). In the total population, the MASES vs. MEI showed the strongest agreement (absolute agreement 96.3%; kappa: 0.86); similar results were obtained in axSpA patients (97.3%; 0.90). In pSpA and PsA patients, the SPARCC vs. MEI (97.2%; 0.90 and 95.4%; 0.83, respectively) showed the strongest agreement. Conclusions These results suggest that the prevalence of patients with enthesitis across SpA subtypes differs depending on the disease and the index used. The MEI and MASES appeared best for assessing enthesis in SpA and axSpA, while the MEI and SPARCC index appeared best for assessing enthesitis in pSpA and PsA.

Background: The objectives were as follows: (a) to identify, among patients with axial spondyloarthritis (axSpA), “clusters” of patients based on the presence of peripheral and extra-musculoskeletal manifestations (EMMs) and (b) to compare the effectiveness of the first anti-TNF drugs across the different clusters after 6 months of follow-up. Methods: An observational and retrospective study of 90 axSpA patients naïve to bDMARDs was conducted. An unsupervised cluster analysis using the “k-means” technique was performed using variables of peripheral and EMMs. Baseline clinical and sociodemographic characteristics were evaluated, and the response to anti-TNF treatment (considering responders as those with an improvement ≥1.1 for the Ankylosing Spondylitis Disease Activity Score (ASDAS) or ≥2.0 for the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) was compared across the clusters after 6 months of follow-up. Results: Two clusters were identified: cluster 1 (n = 14), with a higher prevalence of peripheral manifestations, inflammatory bowel disease (IBD), and HLA-B27-positive status, and a lower prevalence of uveitis in comparison with cluster 2 (n = 76). Patients from cluster 1 experienced a more pronounced absolute improvement in ASDAS and BASDAI indices after 6 months. The percentage of responders after 6 months of follow-up was superior in cluster 1 compared to cluster 2 (85.7% vs. 48.7%, p = 0.011). Conclusion: This study suggests the existence of two clinical profiles in axSpA patients according to the peripheral and EMMs, with higher rates of anti-TNF effectiveness after 6 months in those with a greater presence of peripheral features.

Abstract Background Enthesitis represents one of the most important peripheral musculoskeletal manifestations in patients with axial spondyloarthritis (axSpA). However, studies specifically evaluating Achilles tendon enthesitis and its impact over time are scarce. The objectives of this study were to evaluate the impact of Achilles’ tendon enthesitis found at baseline during physical examination on the outcome measures after 2 years of follow-up in patients with ankylosing spondylitis (AS). Methods This was an observational and prospective study conducted during 2 years of follow-up in the REGISPONSER-AS registry. Linear regression models adjusted for age, body mass index (BMI), and anti-TNF intake were conducted to evaluate the association between the presence of Achilles enthesitis at baseline and the patient-reported outcome (PRO) scores at baseline. The impact of this feature on PROs over 2 years of follow-up was evaluated using mixed models for repeated measures adjusted for age, BMI, and anti-TNF intake. Results Among the 749 patients included, 46 patients (6.1%) showed Achilles’ tendon enthesitis during physical examination at the baseline study visit. Patients with Achilles enthesitis had an increase in the global VAS score, BASDAI, mBASDAI, ASDAS-CRP, and BASFI scores in comparison with patients without this feature. In addition, the mean global VAS, BASDAI, and ASDAS-CRP scores were significantly higher among patients with Achilles enthesitis over the 2 years of follow-up after adjusting for age, BMI, and current anti-TNF intake. The percentage of patients achieving ASDAS low disease activity (ASDAS

Objective To describe and analyse the initial symptoms attributable to patients with spondyloarthritis (SpA) and their association with HLA-B27 status.Methods This was an observational, cross-sectional and multicentre study with patients who fulfilled the European Spondyloarthropathy Study Group criteria for SpA from the Registry of Spondyloarthritis of Spanish Rheumatology (REGISPONSER) and Ibero-American Registry of Spondyloarthropathies (RESPONDIA) united registries. Differences in the first sign(s) or symptom(s) were compared across diagnoses and between HLA-B27 status. The diagnostic delay between patients who start the disease with musculoskeletal manifestations (MMs) and extra-MMs (EMMs) was compared.Results A total of 4067 patients were included (2208 from REGISPONSER and 1859 from RESPONDIA) (ankylosing spondylitis (AS): 68.3%, psoriatic arthritis (PsA): 19.9%, undifferentiated SpA: 11.8%). Overall, 3624 (89.1%) patients initiated the disease with MMs and 443 (10.9%) with EMMs. Low back pain (61.7%) and lower-limb arthritis (38.5%) were the most frequent initial symptoms. In AS patients, the absence of HLA-B27 seems to be related to an increase in the probability of starting the disease with cervical pain and peripheral manifestations. In PsA, the onset of arthritis and psoriasis was more prevalent in HLA-B27-negative patients, while initiation with axial manifestations was more predominant in HLA-B27-positive patients. The diagnostic delay was longer in patients with initial MMs than in those with EMMs (7.2 (34.8) vs 4.5 (7.6) years, respectively).Conclusion In this SpA population, MMs were the most prevalent initial symptoms, with differences across diagnoses and depending on the presence of the HLA-B27 antigen.

Objective We aimed to characterize differences of clinical features, extra-musculoskeletal manifestations and treatment utilizations based on the patients’ HLA-B*27 status in a global axSpA cohort and identify predictors of HLA-B*27 negativity in these patients.Methodology In post-hoc analysis of the ASAS-PerSpA study, patients fulfilling the 2009 ASAS classification criteria for axSpA and typed for HLA-B*27 were included. The patient characteristics cwere compared between the HLA-B*27(+) and HLA-B*27(-) subgroups. Multivariablete logistic regression was conducted to identify predictors of HLA-B*27 negativity.Results Of 2910 patients with axSpA from 24 countries, 2269 were tested for HLA-B*27 [1753 HLA-B*27(+) and 516 HLA-B*27(-)]. The proportion of males was higher in the HLA-B*27 (+) compared to the HLA-B*27 (-) subgroup (72.1 vs 54.3%). Patient population with HLA-B*27 (+) more often had positive family history for axSpA (29.8 vs 15.3%), and younger age at diagnosis, 31.6 years (SD 10.9) vs 37.7 years (SD 12.1). HLA-B*27 (-) patients had significantly higher peripheral arthritis (47.5 vs 42.1%, p

Objectives1) To characterize the inflammatory proteome of synovial fluid (SF) from patients with Psoriatic Arthritis (PsA) using a high-quality throughput proteomic platform, and 2) to evaluate its potential to stratify patients according to clinical features.MethodsInflammatory proteome profile of SF from thirteen PsA patients with active knee arthritis were analyzed using proximity extension assay (PEA) technology (Olink Target 96 Inflammation panel). Four patients with OA were included as control group.ResultsSeventy-nine inflammation-related proteins were detected in SF from PsA patients (SF-PsA). Unsupervised analyzes of the molecular proteome profile in SF-PsA identified two specific phenotypes characterized by higher or lower levels of inflammation-related proteins. Clinically, SF-PsA with higher levels of inflammatory proteins also showed increased systemic inflammation and altered glucose and lipid metabolisms. Besides, SF from PsA patients showed 39 out of 79 proteins significantly altered compared to SF-OA specifically related to cell migration and inflammatory response. Among these, molecules such as TNFα, IL-17A, IL-6, IL-10, IL-8, ENRAGE, CCL20, TNFSF-14, OSM, IFNγ, MCP-3, CXCL-11, MCP4, CASP-8, CXCL-6, CD-6, ADA, CXCL-10, TNFβ and IL-7 showed the most significantly change.ConclusionThis is the first study that characterizes the inflammatory landscape of synovial fluid of PsA patients by analyzing a panel of 92 inflammatory proteins using PEA technology. Novel SF proteins have been described as potential pathogenic molecules involved in the pathogenesis of PsA. Despite the flare, inflammatory proteome could distinguish two different phenotypes related to systemic inflammation and lipid and glucose alterations.

Aims To explore the clinical and radiographical characteristics of axial psoriatic arthritis (PsA) and to compare it with ankylosing spondylitis (AS) with psoriasis.Methods Cross-sectional study from the national multicentre registry REGISPONSER where participants fulfilled the European Spondyloarthropathy Study Group spondyloarthritis criteria at entry. Clinical, laboratory and radiographical characteristics between patients classified as axial PsA and AS with psoriasis by their rheumatologist are compared according to HLA-B27 status.Results Of 2367 patients on REGISPONSER, n=405 had PsA, of whom 27% (n=109) had axial involvement as per the treating rheumatologist. 30% (n=26/86) of axial PsA were HLA-B27 positive. In the AS group, 9% (127/1422) had a history of psoriasis and were more frequently male, with longer diagnostic delay and more anterior uveitis than those with axial PsA who had more peripheral involvement and nail disease. Patients with HLA-B27-negative axial PsA reported less inflammatory pain and structural damage compared with AS with psoriasis. By contrast, HLA-B27-positive axial PsA shared clinical characteristics similar to AS and psoriasis although with a lower BASRI score. In the multivariable analysis, patients with AS and psoriasis were independently associated with HLA-B27 positivity (OR 3.34, 95% CI 1.42 to 7.85) and lumbar structural damage scored by BASRI (OR 2.14, 95% CI 1.4 to 3.19).Conclusion The more prevalent axial PsA phenotype is predominantly HLA-B27 negative and presents different clinical and radiological manifestations when compared with AS with psoriasis. There is great heterogeneity in what rheumatologists consider axial PsA from a clinical and imaging perspective, highlighting the need for research into possible genetic drivers and a consensus definition.

Background: Acute anterior uveitis (AAU) is the most frequent extra-musculoskeletal manifestation in spondyloarhtritis (SpA). Previous data on AAU focused on axial disease; therefore, it is not well known whether the clinical characteristics of patients with AAU and recurrent AAU differ between patients with axial and peripheral SpA. Objective: Primary objective was to compare the clinical characteristics of patients with AAU from patients without AAU in axial and peripheral spondyloarthritis (SpA) patients. Secondary objectives were to describe the clinical features of patients with AAU in the subset of patients with peripheral SpA (pSpA) and the clinical characteristics of patients with recurrent AAU in SpA patients. Design: This is an ancillary analysis of the ASAS-PerSpA study which included 3152 patients, 2719 patients with axSpA and 433 with pSpA according to rheumatologist judgement. Methods: Recurrent AAU was defined as the presence of two or more episodes of AAU ever. Univariable and multivariable binary logistic regression analyses were conducted to identify factors associated with the presence of AAU ever and the presence of recurrent AAU. Results: Overall, 663 patients (21%) presented AAU. Of them, 444 (66.9%) presented recurrent episodes. In patients with SpA, HLA-B27 positivity is the most important factor linked to the presence of AAU, odds ratio (OR) = 2.70 (95% CI = 2.04–3.6). In patients with pSpA, HLA-B27 positivity was also the most relevant factor linked to the presence of AAU, OR = 6.08 (95% CI = 2.72–15.68). Moreover, disease duration, younger age and higher body mass index (BMI) were the only factors slightly linked to the presence of recurrent episodes, OR = 1.03 (95% CI = 1.01–1.04), OR = 1.01 (95% CI = 1.00–1.03) and OR = 1.04 (95% CI = 1.01–1.08), respectively. Conclusion: HLA-B27 positivity is the most relevant factor linked to AAU risk in SpA patients, and this association is even stronger in those patients with pSpA. Moreover, our study did not find an association between HLA-B27 positivity and recurrent AAU in SpA patients.

Background: The relationship of psoriasis and spondyloarthritis (SpA) is well-known, and the age of appearance of different manifestations has been described as a determinant of SpA phenotype. However, differences between Spa with psoriasis and psoriatic arthritis (PsA) are still controversial. Objectives: To evaluate whether the time of onset of psoriasis relative to the appearance of rheumatic symptoms in patients with SpA is associated with a clinical phenotype, a rheumatologist’s diagnosis and the evolution of the disease. Design: This was a cross-sectional study with data extracted from the REGISPONSER (Spondyloarthritis Registry of the Spanish Rheumatology Society) registry. Methods: All patients had data available for both psoriasis and SpA dates of onset. Patients were classified into two groups depending on the time of appearance of psoriasis: psoriasis before or after rheumatic symptoms. The clinical characteristics, disease activity, radiographic damage, functional ability and received treatments were compared between the two groups. Moreover, the rheumatologists’ diagnoses were compared between the two groups. Univariate and multivariate logistic regressions were conducted to evaluate the factors associated with each group. Results: A total of 433/2367 (18.3%) patients included in the REGISPONSER database had psoriasis: 330 (76.2%) patients had psoriasis before rheumatic symptoms, and 103 (23.8%) had psoriasis after rheumatic symptoms. Patients with psoriasis before rheumatic symptoms had a shorter disease duration and a lower body mass index, a lower prevalence of both HLA-B27 antigens and anterior uveitis, a higher prevalence of dactylitis and an increase in levels of the erythrocyte sedimentation rate (ESR). Furthermore, a higher prevalence of PsA diagnoses (78.1% versus 56.4%) and a more frequent fulfilment of the CASPAR criteria (57.5% versus 42.2%) were found in these patients. The use of DMARDs was not significantly different between the two groups. Conclusion: The time of appearance of psoriasis is associated with the clinical phenotype of SpA and could determine a diagnosis of PsA by rheumatologists.

Introduction: The aim of the study was to compare the prevalence of comorbidities between patients with axial and peripheral phenotypes and to evaluate the role of psoriasis in such comorbidities. Methods: Patients from the cross-sectional Assessment in SpondyloArthritis Inter-national Society (ASAS)-COMOSPA study were classified as having either the axial (presence of sacroiliitis on X-ray or MRI) or peripheral phenotype (absence of sacroiliitis AND presence of peripheral involvement). Patients with each phenotype were divided into two groups depending on the presence or history of psoriasis. Pair-wise comparisons among the four groups (axial/peripheral phenotype with/without psoriasis) were conducted through univariate logistic regressions and generalized linear mixed models using disease duration and sex as fixed effects and country as random effect. Results: A total of 3291 patients were included in this analysis. The peripheral involvement with psoriasis phenotype showed the highest prevalence of hypertension (44.9%), dyslipidaemia (34%) and diabetes (8.8%), while the axial involvement without psoriasis phenotype exhibited the lowest prevalence of dyslipidaemia (14.2%), diabetes (4.1%) and stroke (0.9%). Among patients with psoriasis, the axial phenotype showed a significantly lower prevalence of hypertension (OR: 0.51, 95% CI: 0.35–0.75) and lower prevalence of Framingham score ⩾15 (OR: 0.57, 95% CI: 0.38–0.85) than patients with peripheral involvement after adjusting for disease duration, sex and country. Among patients with the axial phenotype, patients with psoriasis showed a higher prevalence of hypertension (OR 1.76, 1.40–2.20), dyslipidaemia (OR: 1.99, 95% CI: 1.56–2.53), diabetes (OR: 2.05, 95% CI: 1.39–3.02) and Framingham score ⩾15 (OR: 2.00, 95% CI: 1.57–2.55) than non-psoriatic patients. No differences were found across groups concerning bone metabolism disorders. Conclusion: Both the peripheral phenotype and psoriasis are independently associated with an increased prevalence of cardiovascular risk factors. No differences were found for bone metabolism disorders.

Abstract Background (a) To describe the prevalence and incidence of peripheral arthritis during 5 years of follow-up in recent axial spondyloarthritis (axSpA), (b) to evaluate factors associated with their appearance and (c) to assess their impact on treatment, patient-reported outcomes and sick leave after follow-up. Methods Data from the early axSpA patients from the DESIR cohort (first 5 years of follow-up) were analysed. Prevalence and incidence of peripheral arthritis at each study visit were calculated. A multivariate analysis was performed to evaluate baseline factors associated with the development of the arthritis. The use of drugs, the impact on patient-reported outcomes and days of sick leave were compared in both groups over time. Results Out of the 708 patients included in DESIR, 255 (36.0%) showed at least one episode of arthritis (151 before the inclusion visit and 104 during the follow-up), with an incidence of 3.7 cases per 100 person-years. Patients with peripheral arthritis were more likely (OR, 95%CI) to be aged ≥ 33 years (1.60, 1.12–2.27), non-smokers (1.58, 1.10–2.27) and HLAB27 negative (1.47, 1.04–2.08) and have presented with at least one episode of dactylitis (8.50, 4.96–14.60) and enthesitis (2.00, 1.41–2.84). Patients with peripheral arthritis showed a significant greater use of TNFb, csDMARDs and corticosteroids over follow-up; higher levels on BASDAI (40.46 vs. 34.28) and BASFI (27.89 vs. 22.52); poorer quality of life; and higher number of days of sick leave (17.97 vs. 12.78) over time. Conclusion In recent axSpA, 36% of patients reported peripheral arthritis at any time of the disease, being associated with negative HLAB27, non-smokers and with other peripheral manifestations. Patients with arthritis showed a higher burden of disease.

Objectives To characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world.Methods Cross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated.Results A total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%).Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%).Conclusion These results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.

The main symptom in patients with axial spondyloarthritis (axSpA) is inflammatory back pain, caused principally by inflammation of the sacroiliac joints and the spine. However, not all back pain in patients with axSpA is related to active inflammation: other types of pain can occur in these patients, and may be related to structural damage (e.g. ankylosis), degenerative changes, vertebral fractures or comorbid fibromyalgia, which are not uncommon in these patients. Structural damage and ankylosis may lead to a biomechanical stress, which can lead to chronic mechanical pain; and degenerative changes of the spine may also exist in patients with axSpA also leading to mechanical pain. Osteoporosis is more prevalent in axSpA patients than in the general population, and vertebral fractures may result in acute bone pain, which can persist for several months. Fibromyalgia, which is also more prevalent in patients with chronic inflammatory diseases (including axSpA), presents with widespread pain which can mimic entheseal pain. A correct diagnosis of the origin of the pain is crucial, since treatments and management may differ considerably. Recognizing these causes of pain may be a challenge in clinical practice, especially for fibromyalgia, which can coexist with axSpA and may have a significant impact on biologic drug response. In this review, we provide an update of the most common causes of pain other than inflammatory back pain in axSpA patients, and we discuss the latest management options for such causes.

Objective To estimate the 6-year radiographic progression of sacroiliitis in patients with early spondyloarthritis (SpA).Patients and methods Sacroiliac joint (SIJ) radiographs (baseline and 6 years) of 94 patients with recent-onset SpA from the Esperanza cohort were scored, blindly and in a random order, by nine readers. The modified New York criteria were used to define the presence of sacroiliitis. As the gold standard for radiographic (r) sacroiliitis, the categorical opinion of at least five readers was used. Progression was defined as the shift from non-radiographic (nr) to r-sacroiliitis.Results In the 94 SIJ radiographs (baseline and 6 years), 78/94 (83%) pairs of radiographs had not changed from baseline to 6 years. Sacroiliitis was present in 20 patients at baseline (21.3%) and in 18 (19.2%) patients at 6 years; 11 patients had sacroiliitis at both the baseline and final visits; 9 patients changed from baseline r-sacroiliitis to nr-sacroiliitis at 6 years, and 7 changed from baseline nr-sacroiliitis to r-sacroiliitis at 6 years. The mean continuous change score (range: −8 to +8) was 2.80 at baseline and 2.55 at 6 years (mean net progression of −0.25). The reliability of the readers was fair (mean inter-reader kappa of 0.375 (0.146–0.652) and mean agreement of 73.7% (58.7–90%)).Conclusion In the early SpA Esperanza cohort, progression from nr-axSpA to r-axSpA over 6 years was not observed, although the SIJ radiographs scoring has limitations to detect low levels of radiographic progression.

Comorbidities are defined as coexistent clinical disorders that appear as a consequence of persistent inflammatory activity and/or treatment. Comorbidities in spondyloarthritis (SpA) are frequent, contributing to a poorer quality of life, higher mortality and incremented healthcare costs. Several recommendations for the screening and management of these comorbidities have been developed in recent years with the aim of improving the different outcomes in these patients. Osteoporosis is the most prevalent comorbidity in patients with SpA, mainly caused by systemic inflammation and a lack of mobility, while cardiovascular diseases explain the increased mortality in patients with SpA with regard to the general population. Data from randomised controlled trials show a low incidence of infections in both patients with and without immunosuppressive treatment, and no evidence of a high incidence of malignant diseases has been demonstrated in these patients. Finally, concomitant fibromyalgia deserves attention, since its coexistence with SpA leads to a poorer treatment response and more switches of anti-TNF treatments. In this review, we show an update of the most common comorbidities in patients with SpA, and we discuss the latest evidence on the management of such comorbidities.

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 (β 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 (β 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.

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.

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.

Background: Axial spondyloarthritis (axSpA) affects spinal muscles, due to inflammation and structural damage. The mechanical properties of the muscles, such as tone or stiffness, could be altered in axSpA. The aim of this work is to analyze the mechanical properties of cervical and lumbar spine muscles in axSpA patients and their relationship with metrology measures, function, disease activity, structural damage and quality of life. Methods: axSpA patients and age/gender/BMI matched healthy controls were recruited. The muscle mechanical properties (MMPs), such as tone or frequency, stiffness, decrement (linear elastic properties), relaxation and creep (viscoelastic properties), of cervical (semispinalis capitis) and lumbar (erector spinae) muscles were bilaterally measured at rest using myotonometry. Additionally, conventional metrology, BASMI (metrology index), BASDAI (disease activity index), mSASSS (radiological structural damage index) and SF-12 (health-related quality of life questionnaire) were used in the axSpA group. Between-groups comparison, intra-group correlations and multivariable regression analyses were performed to achieve the study aims. Results: Thirty-four axSpA patients (mean age: 46.21 ± 8.53 y) and 34 healthy volunteers (mean age: 43.97 ± 8.49 y) were recruited. Both in cervical and lumbar spine, linear elastic parameters were significantly higher in axSpA patients in comparison with controls, while viscoelastic parameters were significantly lower. Lumbar muscle frequency, stiffness, relaxation, creep and cervical muscle elasticity were fair to strongly correlated (|0.346| < r < |0.774|) with age, functional status, activity of disease, structural damage and quality of life in axSpA patients. Furthermore, moderate to good fitted multivariate models (0.328 < R2 < 0.697) were obtained combining age, conventional metrology, activity of the disease and function for the estimation of cervical and lumbar MMPs. Conclusion: Mechanical properties of spinal muscles of axSpA patients differ from controls. Lumbar and cervical muscles exhibit greater linear elastic properties and lower viscoelastic properties, which are related with age, clinical and psychophysiological features of axSpA.

Inflammatory and autoimmune processes have been associated with the onset of depressive and psychotic symptoms. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are rheumatic diseases with an inflammatory etiology. A high prevalence of depressive and anxiety-related comorbidity has been reported for both diseases, with no evidence of a greater prevalence of psychosis. The objective of the present study was to evaluate for the first time subclinical psychotic symptoms in patients with RA and SpA. This is a cross-sectional, single-center study including RA and SpA patients, as well as healthy controls. Abnormal psychotic experiences (positive, negative, and depressive symptoms) were evaluated using the Community Assessment of Psychic Experiences (CAPE-42). Functional capacity was evaluated using the Short-Form Health Survey SF-12. We compared the CAPE and SF-12 scores between the three groups. We recruited 385 individuals: 218 with RA, 100 with SpA, and 67 healthy controls. According to the CAPE scale, the frequency of subclinical psychotic symptoms was greater in patients than in healthy controls (RA, 1.90 vs. 1.63, p < 0.001; SpA, 1.88 vs. 1.63, p = 0.001). Distress was also greater in patients than in controls owing to the presence of symptoms. No differences were observed between the three groups for the mental dimension scores in the SF-12 Health Survey (43.75 in RA, 45.54 in SpA, and 43.19 in healthy controls). Our findings point to a greater prevalence of subclinical psychotic symptoms in patients with RA and patients with SpA than in the general population. The results suggest an association between inflammation and depression/subclinical psychotic symptoms.

Axial spondyloarthritis (axSpA) is a rheumatic inflammatory chronic disease that mainly affects the spine, producing inflammation and structural damage at the vertebral level (erosions, syndesmophytes, and bony bridges) [...]

Studies on osteoporosis in axial spondyloarthritis (axSpA) have focused on the lumbar segment, and few studies have assessed bone mineral density (BMD) in the hip and femoral neck in these patients. The aim of this study was to evaluate the prevalence of low BMD and osteopenia in the total hip or femoral neck and the factors associated with these conditions in axSpA patients. This was a single-centre, observational, cross-sectional study among consecutive patients with axSpA according to the ASAS criteria from the CASTRO registry. All patients underwent total hip and femoral neck DXA BMD measurements. Low BMD was defined as a Z-score less than −1, and osteopenia was defined as a T-score less than −1. Multivariate logistic and generalised linear regressions were used to evaluate factors independently associated with low BMD and osteopenia in the hip or femoral neck and those associated with variability in BMD, respectively. A total of 117 patients were included, among which 30.8% were female and the mean age was 45 years. A total of 36.0% of patients had low BMD (28.1% in the total hip and 27.4% in the femoral neck), and 56.0% of patients had osteopenia (44.7% in the total hip and 53.8% in the femoral neck). A multivariate logistic regression showed that age, radiographic sacroiliitis and ASAS-HI were independently associated with low BMD in the total hip or femoral neck. Factors that were independently associated with osteopenia were Body Mass Index, disease duration, radiographic sacroiliitis and ASAS-HI. In conclusion, 36% of the patients with axSpA had low BMD in the total hip or femoral neck. A younger age and radiographic sacroiliitis were the most important factors associated with decreased BMD.

Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterized by the presence of inflammatory back pain. In patients with chronic low back pain, the lumbar flexion relaxation phenomenon measured by surface electromyography (sEMG) differs from that in healthy individuals. However, sEMG activity in axSpA patients has not been studied. The purpose of this study was to analyze the flexion relaxation phenomenon in axSpA patients. A study evaluating 39 axSpA patients and 35 healthy controls was conducted. sEMG activity at the erector spinae muscles was measured during lumbar full flexion movements. sEMG activity was compared between axSpA patients and the controls, as well as between active (BASDAI ≥ 4) and non-active (BASDAI < 4) patients. The reliability (using intraclass correlation coefficients (ICC)), criterion validity and discriminant validity using the area Under the curve (AUC) for the inverse flexion/relaxation ratio (1/FRR) were evaluated. Significant differences (p < 0.05) were observed between axSpA patients and the control group in lumbar electric activity, especially during flexion, relaxation, and extension and in FRR and 1/FRR (0.66 ± 0.39 vs. 0.25 ± 0.19, respectively). In addition, significant differences were found between active and non-active but also between non-active and healthy subjects. The sEMG showed good reliability (ICC > 0.8 for 1/FRR) and criterion validity. ROC analysis showed good discriminant validity for axSpA patients (AUC = 0.835) vs. the control group using 1/FRR. An abnormal flexion/relaxation phenomenon exists in axSpA patients compared with controls. sEMG could be an additional objective tool in the evaluation of patient function and disease activity status.

Portable inertial measurement units (IMUs) are beginning to be used in human motion analysis. These devices can be useful for the evaluation of spinal mobility in individuals with axial spondyloarthritis (axSpA). The objectives of this study were to assess (a) concurrent criterion validity in individuals with axSpA by comparing spinal mobility measured by an IMU sensor-based system vs. optical motion capture as the reference standard; (b) discriminant validity comparing mobility with healthy volunteers; (c) construct validity by comparing mobility results with relevant outcome measures. A total of 70 participants with axSpA and 20 healthy controls were included. Individuals with axSpA completed function and activity questionnaires, and their mobility was measured using conventional metrology for axSpA, an optical motion capture system, and an IMU sensor-based system. The UCOASMI, a metrology index based on measures obtained by motion capture, and the IUCOASMI, the same index using IMU measures, were also calculated. Descriptive and inferential analyses were conducted to show the relationships between outcome measures. There was excellent agreement (ICC > 0.90) between both systems and a significant correlation between the IUCOASMI and conventional metrology (r = 0.91), activity (r = 0.40), function (r = 0.62), quality of life (r = 0.55) and structural change (r = 0.76). This study demonstrates the validity of an IMU system to evaluate spinal mobility in axSpA. These systems are more feasible than optical motion capture systems, and they could be useful in clinical practice.