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

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

Cardiovascular mortality and cardiovascular event rates in patients with inflammatory rheumatic diseases in the CARdiovascular in rheuMAtology (CARMA) prospective study-results at 5 years of follow-up.

OBJECTIVES: To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up. METHODS: This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model. RESULTS: Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE [7.39 cases per 1000 person-years (95% CI 4.63, 11.18)] was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years [hazard ratio 4.60 (P =0.02)], compared with those without CIRD. CONCLUSIONS: Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.

Hyperlipoproteinaemia(a) in patients with spondyloarthritis: results of the Cardiovascular in Rheumatology (CARMA) project.

OBJECTIVES: Cardiovascular (CV) disease is one of the main causes of morbi-mortality in spondyloarthritis (SpA), partially explained by traditional CV risk factors. Information on lipoprotein(a) [Lp(a)], a non-conventional risk factor, in SpA is scarce. In this study we assessed the prevalence of hyperlipoproteinaemia(a) in SpA patients and analysed the possible related factors. METHODS: A baseline analysis was made of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients and controls included in the CARMA project (CARdiovascular in RheuMAtology), a 10-year prospective study evaluating the risk of CV events in chronic inflammatory rheumatic diseases. A multivariate logistic regression model was performed using hyperlipoproteinaemia(a) (Lp(a) >50 mg/dl) as a dependent variable and adjusting for confounding factors. RESULTS: 19.2% (95% CI: 16.80-22.05) of the SpA patients [20.7% (95% CI: 16.91-24.82) of those with AS and 17.7% (95% CI: 14.15-21.75) of those with PsA] and 16.7% (95% CI: 13.23-20.86) of the controls had hyperlipoproteinaemia(a) (p=0.326). Adjusting for age and sex, SpA patients were more likely to have hyperlipoproteinaemia(a) than controls (OR: 1.43, 95%CI: 1.00-2.04; p=0.05), especially those with AS (OR: 1.81, 95%CI: 1.18-2.77; p=0.007). In the adjusted model, apolipoprotein B in all patients, non-steroidal anti-inflammatory drugs in AS, and female sex in PsA, were associated with hyperlipoproteinaemia(a). No disease-specific factors associated with hyperlipoproteinaemia(a) were identified. CONCLUSIONS: SpA patients show a moderately increased risk of hyperlipoproteinaemia(a) compared to controls, especially those with AS. Lp(a) determination may be of interest to improve the CV risk assessment in SpA patients.

Magnetic resonance imaging assessment in patients with axial spondyloarthritis: development of checklists for use in clinical practice.

The objective of our study was to standardize magnetic resonance imaging (MRI) assessment of spine and sacroiliac joints in patients with axial spondyloarthritis (axSpA) and/or inflammatory spinal pain, by creating checklists and templates based on the opinions of rheumatologists and radiologists. A scientific committee developed a series of questionnaires with multiple items regarding MRI in patients with axial inflammatory pain and/or axSpA. Then an expert panel of rheumatologists and radiologists rated all items in a 9-point Likert scale. Finally, the scientific committee and the expert panel met to create the definitive documents. Several definitive checklists and templates were generated for rheumatologist-requested MRI and for radiologist-requested MRI reports of sacroiliac joint and spinal examinations. A technical requirement protocol was also agreed on. Our results could be useful in increasing understanding between rheumatologists and radiologists regarding MRI in axSpA diagnosis and follow-up.

The EJES-3D tool for personalized prescription of exercise in axial spondyloarthritis through multimedia animations: pilot study.

To develop and evaluate a web application based on multimedia animations, combined with a training program, to improve the prescription of exercises in spondyloarthritis (SpA). After a review of exercises included in the main clinical trials and recommendations of international societies, a multidisciplinary team-rehabilitators, rheumatologists, physiotherapists, computer scientists and graphic designers-developed a web application for the prescription of exercises (EJES-3D). Once completed, this was presented to 12 pairs of rehabilitators-rheumatologists from the same hospital in a workshop. Knowledge about exercise was tested in rheumatologists before and 6 months after the workshop, when they also evaluated the application. The EJES-3D application includes 38 multimedia videos and allows prescribing predesigned programs or customizing them. A patient can consult the prescribed exercises at any time from a device with internet connection (mobile, tablet, or computer). The vast majority of the evaluators (89%) were satisfied or very satisfied and considered that their expectations regarding the usefulness of the web application had been met. They highlighted the ability to tailor exercises adapted to the different stages of the disease and the quality and variety of the videos. They also indicated some limitations of the application and operational problems. The EJES-3D tool was positively evaluated by experts in SpA, potentially the most demanding group of users with the most critical capacity. This allows a preliminary validation of the contents, usefulness, and ease of use. Analyzing and correcting the errors and limitations detected is allowing us to improve the EJES-3D tool.

Differences between familial and sporadic early spondyloarthritis: results from the ESPERANZA cohort.

OBJECTIVES: To describe and evaluate clinical and imaging differences between patients with familial and sporadic early spondyloarthritis (SpA). METHODS: This was a cross-sectional study analysing the baseline dataset from ESPERANZA, a national programme developed for the early identification of patients with SpA. Patients fulfilling SpA ASAS classification criteria were included. Familial SpA was defined according to the ASAS/ESSG criteria as the presence in first- or second-degree relatives of any of the following: ankylosing spondylitis, psoriasis, uveitis, reactive arthritis, and inflammatory bowel disease. Socio-demographic and disease characteristics, disease activity, metrology and laboratory and imaging data were compared by descriptive and bivariate statistics. RESULTS: A total of 377 patients were included - 64% men, mean age 32, and mean disease duration 12 months. Out of these, 132 (35%) patients (101 axial and 31 peripheral SpA) were familial forms. In patients with axial SpA, statistically significant differences (p<0.05) were found between familial and sporadic forms regarding age at symptoms onset (29.4±9.2 vs. 31.5±10 years), HLA B27 positivity (83% vs. 71%), BASMI (1.2± 13 vs. 1.6 1.2) and sacroiliitis on magnetic resonance imaging (36% vs. 47%), respectively. In patients with peripheral SpA, there were no significant differences for any of the variables analysed. CONCLUSIONS: Familial axial SpA presents symptoms at a younger age, is more frequently HLA-B27 positive and shows better spinal mobility than sporadic axial SpA; this latter presenting sacroiliitis on MRI more frequently than familial axial SpA. Apparently, no differences exist in the expression of familial or sporadic peripheral SpA.

Standards of care for patients with spondyloarthritis.

To define and give priory to standards of care in patients with spondyloarthritis (SpA). A systematic literature review on SpA standards of care and a specific search in relevant and related sources was performed. An expert panel was established who developed the standards of care and graded their priority (high, mild, low, or no priority) following qualitative methodology and Delphi process. An electronic survey was sent to a representative sample of 167 rheumatologists all around the country, who also gave priority to the standards of care (same scale). A descriptive analysis is presented. The systematic literature review retrieved no article specifically related to SpA patients. A total of 38 standards of care were obtained-12 related to structure, 20 to process, and 6 to result. Access to care, treatment, and safety standards of care were given a high priority by most of rheumatologists. Standards not directly connected to daily practice were not given such priority, as standards which included a time framework. The standards generated for the performance evaluation (including patient and professionals satisfaction) were not considered especially important in general. This set of standards of care should help improve the quality of care in SpA patients.

Elevating the Standard of Care for Patients with Axial Spondyloarthritis: 'Calls to Action' from Rheumacensus, a Multistakeholder Pan-European Initiative.

INTRODUCTION: Several barriers to optimal care in axial spondyloarthritis (axSpA) exist, which is detrimental to patient outcomes. The Rheumacensus programme aimed to identify how the standard of care (SoC) and treatment ambition for patients with axSpA could be elevated, from the unique perspective of three key stakeholders from across Europe: patients, healthcare professionals (HCPs) and payors. METHODS: Rheumacensus followed three phases: an insights-gathering workshop to identify current unmet needs in axSpA and an area of focus, a modified Delphi process to gain consensus on improvements within the agreed area of focus, and a Consensus Council (CC) meeting to generate 'Calls to Action' (CTA) to highlight the changes needed to elevate the SoC for patients with axSpA. RESULTS: The Rheumacensus CC consisted of four patient representatives, four HCPs and four payors. All 12 members completed all three Delphi e-consultations. The shared area of focus that informed the Delphi process was patient empowerment through education on the disease and treatment options available, to enable patient involvement in management and ultimately increase treatment adherence. Four key themes emerged from the Delphi process: patient empowerment, patient knowledge, patient-HCP consultations and optimal initial treatment. These themes informed 11 overarching CTA, which demonstrate the need for a multistakeholder approach to implement a paradigm shift towards patient-centred care to elevate health outcomes in patients with axSpA. CONCLUSION: Rheumacensus identified CTA to help bridge the disparities observed in axSpA care. It is now imperative for all stakeholders to take practical steps towards addressing these CTA to elevate the SoC and treatment ambition in patients with axSpA.

Axial spondyloarthritis (axSpA) is a long-term inflammatory disease involving the spine and other joints of the body as well as where tendons and ligaments attach to bone. AxSpA is associated with a significant burden to patients which can be worsened by delays in diagnosis and poor disease management. This report is about a programme called Rheumacensus which has the overall aim of improving the standard of care (SoC) for patients with axSpA. Rheumacensus brings together the points of view of three key groups involved in the care of people with axSpA: patients, payors and healthcare professionals (HCPs) from across Europe. Together, these three groups agreed to focus on patient empowerment through education on the disease and treatment options to effectively enhance treatment adherence, as a way to raise the SoC. Through a series of exercises­to agree on the current SoC and what needs to be improved­and group discussions, four themes were established which were used by the groups to help them suggest 'Calls to action' (CTA). The CTAs were ideas of how improvements could be made or what needs to be done to improve the care patients receive. The four themes were (1) patient empowerment, (2) patient knowledge, (3) patient­HCP consultation and (4) optimal initial treatment. In total, 11 CTAs were developed across these themes that provide direction and practical next steps which patients, payors and HCPs could take to drive change and make a real difference to patients by improving their care.

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

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

Disease control in patients with ankylosing spondylitis in real clinical practice in Spain: Results of the MIDAS study.

INTRODUCTION AND OBJECTIVES: Understanding the disease activity is fundamental to improve patient prognosis and patients' quality of life. MiDAS study described disease activity in ankylosing spondylitis (AS) Spanish patients and the proportion of them with controlled disease. METHODS: Observational, cross-sectional, multicenter study carried out under conditions of routine clinical practice. Adult (≥18 years) patients with ≥6 months since AS diagnosis treated ≥3 months prior to inclusion. The primary endpoint was the percentage of patients with low disease activity assessed through BASDAI (primary endpoint) and ASDAS-CRP (secondary endpoint). RESULTS: 313 AS patients included: 75.7% male; 78.5% HLA-B*27 positive; mean (SD) baseline age of 50.4 (12.0) years; mean (SD) disease duration of 15.5 (11.6) years; 73.5% were treated with biological disease-modifying antirheumatic drugs (DMARDs), 22.4% with non-biological DMARDs and 53.7% with non-steroidal anti-inflammatory drugs, alone or in combination. Monotherapy with biologics and non-biologics was used by 29.7% and 26.8% of patients, respectively. According to BASDAI, 38.0% were in remission (BASDAI≤2) and 64.5% showed adequate disease control (BASDAI<4). According to ASDAS-CRP, 29.4% achieved remission (ASDAS-CRP<1.3) and 28.1% low disease activity (1.3≤ASDAS-CRP<2.1). CONCLUSIONS: Almost two thirds of the AS patients recruited had low disease activity, with about one third of them being in remission (BASDAI≤2, ASDAS-CRP<1.3). These results highlight the existing room for improvement in treating AS patients in clinical practice.

Resources and strategies for the optimal care of patients with axial spondyloarthritis: The CREA project.

BACKGROUND AND OBJECTIVE: Axial spondyloarthritis (axSpA) are musculoskeletal diseases with different manifestations. In clinical practice, variability, and limitations in the collection of the outcomes required for follow-up have been observed. The objective of the CREA project was to agree on improvement strategies for the initial assessment and follow-up of patients with axSpA in Spain. MATERIALS AND METHODS: A survey with 33 questions was conducted by a representative sample of rheumatologists on clinical practice, resources, and present limitations in the follow-up of patients with axSpA. The results of the survey were discussed in 10 regional meetings, and 105 strategies were proposed and evaluated through a Delphi consensus in which 85 experts participated. RESULTS: The lack of time for clinical visits, the lack of nurses and/or support staff and the delay in performing the imaging tests were the most prominent limitations in the follow-up of patients with axSpA. One hundred and five strategies were proposed related to the evaluation of disease activity, physical function, quality of life and disease impact, to the evaluation of comorbidities and extra-articular manifestations, laboratory tests; imaging tests, physical examination and metrology. Of the total, 85 were considered highly advisable. No regional differences were found. CONCLUSIONS: The proposals agreed upon as highly advisable in the present study are applicable to the entire national territory, allow tighter and more homogeneous monitoring of the patients with axSpA, facilitate more comprehensive management of the disease, and respond to the unmet needs detected in the initial survey.

Disease control in patients with psoriatic arthritis in real clinical practice in Spain: MiDAS study.

OBJECTIVE: MiDAS study assessed the percentage of psoriatic arthritis (PsA) patients treated in routine clinical practice who achieved control of disease activity according to Disease Activity in Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA). METHODS: Observational, non-interventional, cross-sectional, multicenter study conducted under conditions of routine clinical practice in 36 centers with outpatient rheumatology clinics in Spanish public hospitals. Patients included were adults (≥18 years) with ≥6 months PsA diagnosis according to classification for PsA (CASPAR) criteria and undergoing treatment ≥3 months. The main variable evaluated was the percentage of patients under remission and low disease activity, assessed through DAPSA and MDA. RESULTS: 313 patients with PsA were included: 54.3% male; with mean age of 54.1±12.2 years and mean disease duration of 10.5±9.0 years. Mean C-reactive protein (CRP) serum levels were 4.9±7.3mg/L. At the study visit, 58.5% of patients were in monotherapy (17.6% biological and 40.9% non-biological) and 41.2% were receiving biological and non-biological therapy. 59.4% of patients showed low disease activity (DAPSA≤14) and 19.8% were on remission (DAPSA≤4). Moreover, 51.4% of the patients reached an MDA status (≥5 MDA). CONCLUSIONS: Around 40% of PsA patients presented uncontrolled disease, highlighting the need to improve the management of these patients in clinical practice.

The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αß) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.

Female Sex, Age, and Unfavorable Response to Tumor Necrosis Factor Inhibitors in Patients With Axial Spondyloarthritis: Results of Statistical and Artificial Intelligence-Based Data Analyses of a National Multicenter Prospective Registry.

OBJECTIVE: Real-world studies are needed to identify factors associated with response to biologic therapies in patients with axial spondyloarthritis (SpA). The objective was to assess sex differences in response to tumor necrosis factor inhibitors (TNFi) and to explore possible risk factors associated with TNFi efficacy. METHODS: A total of 969 patients with axial SpA (315 females, 654 males) enrolled in the BIOBADASER registry (2000-2019) who initiated a TNFi (first, second, or further lines) were studied. Statistical and artificial intelligence (AI)-based data analyses were used to explore the association of sex differences and other factors to TNFi response, using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), to calculate the BASDAI50, with an improvement of at least 50% of the BASDAI score, and using the Ankylosing Spondylitis Disease Activity Score, calculated using the C-reactive protein level (ASDAS-CRP). RESULTS: Females had a lower probability of reaching a BASDAI50 response with a first line TNFi treatment at the second year of follow-up (P = 0.018) and a lesser reduction of the ASDAS-CRP at this time point. The logistic regression model showed lower BASDAI50 responses to TNFi in females (P = 0.05). Other factors, such as older age (P = 0.004), were associated with unfavorable responses. The AI data analyses reinforced the idea that age at the beginning of the treatment was the main factor associated with an unfavorable response. The combination of age with other clinical characteristics (female sex or cardiovascular risk factors and events) potentially contributed to an unfavorable response to TNFi. CONCLUSION: In this national multicenter registry, female sex was associated with less response to a first-line TNFi by the second year of follow-up. A higher age at the start of the TNFi was the main factor associated with an unfavorable response to TNFi.

Corrigendum: The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

[This corrects the article DOI: 10.3389/fimmu.2023.1191782.].

Strategies and resources to optimise the management of Psoriatic Arthritis patients: The CREA Project.

BACKGROUND AND AIM: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease that affects the musculoskeletal system and skin, and manifests heterogeneously, with a variable course. In current clinical practice, variability and limitations in its follow-up have been observed. The aim of the CREA project was to agree on strategies to improve the initial assessment and follow-up of patients with PsA in Spain. MATERIALS AND METHODS: A survey was conducted among a representative sample of expert rheumatologists in Spain, containing 33 questions on current clinical practice, available resources, and current limitations in the follow-up of patients with PsA. The results were discussed in regional meetings and 105 strategies were proposed and finally evaluated by 85 experts in a Delphi consensus. RESULTS: The most important limitations in the follow-up of PsA were lack of consultation time, lack of nursing staff, and delays in performing imaging tests. A total of 108 strategies were proposed related to the assessment of quality of life and disease-impact indices; comorbidities and extra-articular manifestations; laboratory tests; imaging tests; physical examination and metrology; and activity and function indices. Of the total, 53 were considered highly advisable, with no regional differences in consensus values. DISCUSSION AND CONCLUSIONS: The proposals offered in the current study are applicable to the entire country, respond to the unmet needs detected in the initial survey, form a minimum action framework, and ensure optimal follow-up of patients with PsA.

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

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

Treatment Failure in Axial Spondyloarthritis: Insights for a Standardized Definition.

Axial spondyloarthritis is a chronic inflammatory rheumatic disease that affects the axial skeleton and causes severe pain and disability. It may be also associated with extra-articular manifestations. Early diagnosis and appropriate treatment can reduce the severity of the disease and the risk of progression. The biological disease-modifying antirheumatic drugs (bDMARDs) tumor necrosis factor alpha (TNFα) inhibitors (TNFi) and the anti-interleukin (IL)-17A antibodies secukinumab and ixekizumab are effective agents to reduce disease activity and minimize the inflammation that damages the joints. New alternatives such as Janus kinase (JAK) inhibitors are also available. Unfortunately, response rates to bDMARDs are far from optimal, and many patients experience so-called treatment failure. The definition of treatment failure definition is often vague and may depend on the rigorousness of the therapeutic goal, the inclusion or not of peripheral symptoms/extra-articular manifestations, or patients' overall health. After an exhaustive bibliographic review, we propose a definition based on loss of the following status: low disease activity assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, absence of extra-articular manifestations, and low disease impact on the patients' general health. Apart from discontinuing the therapy because of safety or intolerance reasons, two types of treatment failure can be differentiated depending on when it occurs: primary failure (no response within 6 months after treatment initiation, or lack of efficacy) and secondary failure (response within 6 months but lost thereafter, or loss of efficacy over time). Physicians should carefully consider the moment and the reason for the treatment failure to decide the next therapeutic step. In the case of primary failure on a first TNFi, it seems reasonable to switch to another class of drugs, i.e., an anti-IL-17 agent, as phase III trials showed that the response to IL-17 blockade was higher than to placebo in patients previously exposed to TNFi. When secondary failure occurs, and loss of efficacy is suspected to be caused by antidrug antibodies (ADAs), it is advisable to analyze serum TNFi and ADAs concentrations, if possible; in the presence of ADAs and low TNFi levels, changing the TNFi is rational as it may restore the TNFα blocking capacity. If ADAs are absent/low with adequate drug therapeutic levels, switching to another target might be the best strategy.

Disease activity indexes might not capture the same disease aspects in males and females with ankylosing spondylitis: A real-world nationwide analysis.

Background: To evaluate gender differences in disease activity and health status (HS) in patients with radiographic axial spondyloarthritis (r-axSpA)/ankylosing spondylitis (AS). Methods: Ancillary analysis of the MIDAS study, an observational, non-interventional, cross-sectional and retrospective multicenter nationwide study to assess disease activity and its relationship with HS in clinical practice. Adult patients with AS diagnosis, fulfilling ASAS and modified New York criteria, treated for ≥3 months upon study inclusion according to clinical practice were included. The primary outcome was "disease control" assessed by the percentage of patients in remission and low disease activity (BASDAI and ASDAS-CRP scores). HS was evaluated using the ASAS health index (ASAS-HI). Patients' responses and characteristics were analyzed by gender. Results: We analyzed 313 patients with AS, 237 (75.7%) males and 76 (24.3%) females. A total of 202 (64.5%) patients had adequate disease control (BASDAI < 4); 69.2% of males [mean (SD) BASDAI 2.9 (2.1)] and 50.0% of females [mean (SD) BASDAI 3.8 (2.4); p = 0.01]. According to ASDAS-CRP, 57.5% of patients were adequately controlled (ASDAS-ID +ASDAS-LDA); 138 (58.2%) males and 42 (55.3%) females. The mean (SD) ASDAS-CRP was 1.9 (1.1); being 1.9 (1.0) in males and 2.0 (1.1) in females. Overall, the impact of AS on HS was low to moderate [mean (SD) ASAS-HI 5.8 (4.4)]; being 5.5 (4.4) for males and 6.8 (4.2) for females (p = 0.02). Conclusion: This study showed a higher proportion of females with AS and active disease using the BASDAI definition. When using the ASDAS-CRP definition these differences by gender were less pronounced. The impact of disease activity on HS appears to be higher in females than males.