Eduardo Collantes-Estevez

Exercise is recommended in axial spondyloarthritis (axSpA), yet evidence on habitual exercise in routine care and whether its association with disease acti

Objective: Pain in spondyloarthritis reflects not only inflammatory activity but also social context. We quantified the association between a composite Social Factors Index (SFI) and patient‐reported pain severity on the Visual Analog Scale (VAS). Methods: We analyzed 2,042 patients from REGISPONSER (N = 1,514) and RESPONDIA (N = 528). Missing data were handled with multiple imputation (m = 20). The SFI combined education, employment, housing, income source, and Graffar class using penalized regression (sparse‐group lasso). Mutual information (MI) quantified the SFI's relative importance. Propensity scores (logistic regression) supported 1:1 caliper matching (0.2 SD on the logit), comparing the highest (Q4) and lowest (Q1) SFI quartiles. Results: Before matching, Q1 and Q4 included on average 918 and 829 patients per imputation, differing mainly in race (White 80.8% vs 86.8%; standardized mean difference [SMD] = −0.16) and country (Spain 66.2% vs 78.2%; SMD = −0.27). After matching, a mean of 745 pairs (range 731–761) were retained with excellent covariate balance (all |SMD| < 0.10). In the matched sample, patients in Q4 reported higher pain (average treatment effect on the treated +0.38 VAS points; 95% confidence interval [CI] 0.05–0.71; P = 0.023). Postmatching regression yielded an identical estimate (β = +0.37; 95% CI 0.04–0.70; P = 0.030). MI indicated the SFI carried more information about VAS than any single social variable. Stratified analyses suggested heterogeneity: Spain +0.31 (95% CI 0.08–0.71) and Latin America +0.62 (95% CI −0.22 to 1.45). Conclusion: Social disadvantage, summarized by the SFI, is independently associated with greater pain severity in spondyloarthritis after adjustment. These findings support incorporating social determinants into clinical assessment and pain management.

Objectives: To assess the incidence rate of anterior acute uveitis (AAU) in patients with longstanding axial spondyloarthritis (axSpA); to evaluate demographic and clinical characteristics associated with AAU development; and to determine the influence of AAU on bDMARD initiation and retention in this population. Methods: This two-timepoint cohort study analysed data from patients enrolled in the Spanish SpA registry REGISPONSER (2004–2007), who were re-evaluated 17 years later in the REGISPON-3 follow-up study (2021–2023). Information on the date of first AAU episode and bDMARD initiation was collected. Kaplan–Meier and Cox proportional hazards models were used to assess AAU incidence, predictors, and its association with time to bDMARD initiation and treatment retention. Results: A total of 299 patients with longstanding axSpA were included, of whom 33.4% experienced at least one episode of AAU, corresponding to an incidence rate of 1.15 per 100 person-years. The cumulative probability of a first episode of AAU increased with disease duration. The relative risk for developing a second episode after the first, compared to the overall risk of any episode in the total population, was 1.85 (95% CI: 1.34–2.57). In multivariable cox analysis, female sex and baseline enthesitis were independently associated with a higher risk of AAU. AAU did not significantly affect the likelihood of subsequent bDMARD initiation, with similar cumulative treatment probabilities in patients with and without AAU. Among treated patients, adalimumab was more frequently prescribed in those with a history of AAU. bDMARD retention rates at two and five years were comparable regardless of AAU status, suggesting that AAU was not associated with long-term treatment persistence. Conclusions: In patients with longstanding axSpA, the incidence of AAU increased steadily over time. However, the presence of AAU did not significantly influence bDMARD initiation or long-term retention in routine clinical practice.

Objectives: To evaluate whether the diagnostic delay in patients with radiographic axial spondyloarthritis (r-axSpA) is associated with poorer short-term outcomes after two years of follow-up. Methods: This was an observational, longitudinal, and prospective study including patients with r-axSpA from the national multicentre Spanish REGISPONSER-AS registry. Patients were divided into two groups according to the mean diagnostic delay (<5 years, ≥5 years). Binary logistic regression models adjusted for disease duration were constructed and used to evaluate the association between diagnostic delay and disease outcomes at two years. The retention rate for first-line treatment with anti-TNF across the groups was evaluated using a log-rank test. Results: A total of 565 patents were included. The mean diagnostic delay was 5.6 ± 6.2 years, with 325 patients experiencing a delay of <5 years and 240 patients experiencing a delay of ≥5 years. A diagnostic delay of ≥5 years was associated, after 2 years, with a higher prevalence of inflammatory bowel disease (IBD) (OR 2.01 (95%CI 1.06–3.83)), a lower prevalence of synovitis (OR 0.68 (95%CI 0.47–0.98)) and dactylitis (OR 0.24 (95%CI 0.11–0.55)), and worse disease activity after adjusting by disease duration. However, no impact was observed on quality of life, structural damage, or work disability, probably due to the short follow-up period. Finally, no differences between the groups were found with regard to the retention rate for first-line anti-TNF treatment. Conclusions: Diagnostic delay is associated with poorer short-term outcomes in terms of structural damage, dactylitis, and disability in patients with r-axSpA.

J Rheumatol 2025; doi:10.3899/jrheum.2024-1085The funding statement has been revised to the following: "This study was partially funded by the SER-GRESSER/JANSSEN grant, with no involvement from Janssen in its development."This correction applies only to the February 15 2025 First Release. The correct text appears in the print and online issues.

Objective: To compare the clinical and sociodemographic characteristics of Ibero-American patients with radiographic axial spondyloarthritis (r-axSpA) to those of European patients with r-axSpA, with a particular focus on the influence of HLA-B27. Methods: This was an observational, cross-sectional, and multicenter study of 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). Univariate and multivariate analyses between European and Ibero-American populations stratified by HLA-B27 status were conducted. Race stratification (White, Black American, and American Indian) was also performed to evaluate clinical differences according to HLA-B27. Results: A total of 2592 patients with a clinical diagnosis of r-axSpA were included in the analysis: 1083 (41.8%) Ibero-American patients and 1509 (58.2%) European patients. Among the patients who were HLA-B27 positive, Ibero-American status was independently associated with conventional synthetic disease-modifying antirheumatic drug (csDMARD) intake (odds ratio [OR] 4.21), arthritis (OR 2.33), enthesitis (OR 6.01), dactylitis (OR 6.10), severe structural damage (Bath Ankylosing Spondylitis Radiological Index [BASRI]; OR 1.12), and poor functionality (Bath Ankylosing Spondylitis Functional Index; OR 1.40). Multivariate analysis of patients who were HLA-B27 negative revealed that Ibero-American status was independently associated with enthesitis (OR 11.67), csDMARDs (OR 15.51), and total BASRI (OR 1.34). Clinical manifestations also varied across racial groups, with differences noted in the prevalence of peripheral joint manifestations, such as more arthritis and enthesitis in American Indian patients than in White and Black American patients. Conclusion: Ibero-American patients with r-axSpA in our study exhibit more peripheral manifestations, more structural damage, and worse functionality than European patients, regardless of the presence of HLA-B27.

Background: Switching to biosimilars is an effective and safe practice in treating inflammatory diseases; however, a nocebo effect may arise as a result of the way in which the switch is communicated to a given patient. Objective: We aimed to design a gaming-based digital educational tool (including a discussion algorithm) to support the training of health care professionals in efficiently communicating the switch to biosimilars, minimizing the generation of a nocebo effect and thus serving as an implementation strategy for the recommended switch. Methods: The tool was developed based on interviews and focus group discussions with key stakeholders, both patients and health care professionals. Messages likely to either generate trust or to trigger a nocebo effect were generated on the basis of the interviews and focus group discussions. Results: A total 7 clinicians and 4 nurses specializing in rheumatology, gastroenterology, and dermatology, with balanced levels of responsibility and experience, as well as balance between geographic regions, participated in the structured direct interviews and provided a list of arguments they commonly used, or saw used, to justify the switching, and objections given by the patients they attended. Patients with immune-mediated inflammatory diseases who were taking biologic drugs with (n=4) and without (n=5) experience in switching attended the focus groups and interviews. Major topics of discussion were the reason for the change, the nature of biosimilars, and their quality, safety, efficacy, and cost. Based on these discussions, a list of objections and of potential arguments was produced. Patients and health care professionals rated the arguments for their potential to evoke trust or a nocebo effect. Two sets of arguments, related to savings and sustainability, showed discrepant ratings between patients and health care professionals. Objections and arguments were organized by categories and incorporated into the tool as algorithms. The educators then developed additional arguments (with inadequate answers) to complement the valid ones worked on in the focus groups. The tool was then developed as a collection of clinical situations or vignettes that appear randomly to the user, who then has to choose an argument to counteract the given objections. After each interaction, the tool provides feedback. The tool was further supported by accredited medical training on biosimilars and switching. Conclusions: We have developed a digital training tool to improve communication on switching to biosimilars in the clinic and prevent a nocebo effect based on broad and in-depth experiences of patients and health care professionals. The validation of this implementation strategy is ongoing.

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.

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