Abstract
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.
The term spondyloarthritis (SpA) encompasses a heterogeneous group of chronic inflammatory diseases characterized by axial skeleton involvement, peripheral manifestations, and extramusculoskeletal features (such as psoriasis [PsO], uveitis, and inflammatory bowel disease [IBD]) that are strongly associated with the HLA-B27 antigen.1
Despite advancements in understanding and treating SpA, considerable variability in its clinical presentation and disease severity exists among different geographic areas and racial and ethnic groups that should be investigated.2-5 Variations in SpA incidence, clinical manifestations, and treatment response have been observed between Ibero-American and European populations, thus suggesting influences from genetic, environmental, and socioeconomic factors.6
Previous literature suggests a greater prevalence of peripheral arthritis and enthesitis among patients from Latin America than among those from Europe.6,7 One factor that has been potentially implicated in the observed disparities is the differential distribution of the HLA-B27 antigen. Studies have consistently reported lower frequencies of this antigen among Latin American cohorts,8-10 which could be linked to differences in disease expression, with lower rates of axial involvement but a greater incidence of peripheral manifestations.11-14 However, to our knowledge, no studies have evaluated whether the HLA-B27–positive phenotype differs between patients from European and Latin American countries.
Studies exploring the relationship between race and SpA have demonstrated disparities across different racial and ethnic groups.15-17 For instance, research suggests that certain racial groups, such as Black American patients from South Africa, may experience a greater burden of SpA than White patients, with more peripheral manifestations, structural damage, and worse quality of life.15 However, to date, few comparative studies have explored how these racial, ethnic, and geographic differences affect the clinical presentation and management of SpA. Moreover, to our knowledge, no studies have evaluated these differences according to the presence of HLA-B27 to confirm or refute whether differences in phenotypes between European and Latin American patients are because of the unbalanced distribution of this antigen. Hence, it is crucial to investigate and better understand geographic, racial, and ethnic disparities in SpA to enhance diagnosis, treatment, and disease management across diverse populations.
In this study, we aimed to compare the clinical and sociodemographic characteristics of Ibero-American patients with radiographic axial SpA (r-axSpA) to those of European patients with r-axSpA, with a particular focus on the influence of HLA-B27. Additionally, we performed a secondary analysis to explore the effect of racial stratification (White, Black American, and American Indian) on clinical manifestations and HLA-B27 prevalence. We compared these factors by using data from 2 databases: the Registry of Spondyloarthritis of Spanish Rheumatology (REGISPONSER) and the Ibero-American Registry of Spondyloarthropathies (RESPONDIA).
METHODS
Design. This was an observational, cross-sectional, multicenter study that included patients diagnosed with r-axSpA (according to the rheumatologist’s opinion) from the REGISPONSER and RESPONDIA databases. REGISPONSER and RESPONDIA share the same variables and case report form, thus allowing the merging of both registries.
Patients. REGISPONSER is a national, multicenter registry that includes patients with SpA according to the European Spondyloarthropathy Study Group (ESSG) criteria,18 conducted from March 2004 to March 2007. This study was conducted by the Spanish Group for the Study of Spondyloarthritis of the Spanish Society of Rheumatology, which has 31 participating centers. Patients were consecutively included based on the following inclusion criteria: (1) met the ESSG classification criteria, (2) had blood analysis results available within 15 days of the inclusion visit and had completed a radiographic study within the previous year, and (3) agreed to complete all the self-administered questionnaires. Patients could be included at any stage of their disease and were cross-sectionally evaluated.19
The RESPONDIA registry has a similar design and shared the same data collection form and variables with REGISPONSER.20 It was conducted between 2006 and 2007 and involved 33 centers across 10 countries—2 of which were excluded from the analyses due to a low number of patients—in the Americas and Portugal. The inclusion criteria were the same as those in REGISPONSER.
The overall study population included 4410 patients (2366 from REGISPONSER and 2044 from RESPONDIA). However, for this specific analysis, we focused on patients with a diagnosis of ankylosing spondylitis (r-axSpA according to the nomenclature of the Assessment of Spondyloarthritis international Society [ASAS] criteria), totaling 2592 patients with r-axSpA. The total population was divided into European patients (Spain and Portugal; n = 1509 [58.2%]) and Ibero-American patients (Argentina, Brazil, Chile, Costa Rica, Mexico, Peru, Uruguay, and Venezuela; n = 1083 [41.8%]) once both registries were combined. This decision was based on the geographic, socioeconomic, and genetic context shared by Spain and Portugal with the rest of Europe, distinguishing them from Latin American and Brazilian countries. Despite some differences with other European regions, such as different subtypes of HLA-B27 in Northern Europe,21,22 Spain and Portugal share key European characteristics, such as healthcare systems, socioeconomic standards, and genetic markers, justifying their categorization as Europeans. Spanish patients were included in the REGISPONSER registry, and Portuguese patients were grouped with Spain for consistency and clarity.
Variables. From the REGISPONSER and RESPONDIA registries, we collected the following data:
Demographic data: The demographic data included age, sex, race (White, Black American, and American Indian), smoking status, physical exercise, disability status, and education level. Identifying the patient’s race was performed following ethical standards and established research guidelines. This information was collected through patient interviews or using previously established medical records.
Clinical data: Clinical data on musculoskeletal manifestations (alternating buttock pain, asymmetric or lower limb arthritis, enthesitis, and dactylitis) and extramusculoskeletal manifestations (PsO, uveitis, and IBD) were collected. Radiographic images of patients with sacroiliitis were also collected according to the modified New York criteria and evaluated by a local investigator.23 The diagnostic delay (years between symptom onset and disease diagnosis), time since diagnosis (years between disease diagnosis and study visit), and time since symptom onset (years between symptom onset and study visit) were also collected.
Disease activity data: Disease activity data, including the C-reactive protein level, erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI),24 and Axial Spondyloarthritis Disease Activity Score (ASDAS),25 were collected for all the patients.
Function and structural damage data: To assess function and structural damage, the Bath Ankylosing Spondylitis Functional Index (BASFI)26 and Bath Ankylosing Spondylitis Radiological Index (BASRI)27 were collected.
Treatment data: For treatment, data on concurrent and/or previous treatments, such as nonsteroidal antiinflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; sulfasalazine, methotrexate, or leflunomide), and biologic DMARDs (bDMARDs; tumor necrosis factor inhibitor treatment), were collected.
Statistical analysis. First, a descriptive analysis of the clinical and sociodemographic characteristics of the included patients was conducted. Descriptive data are expressed as the mean (SD) for quantitative variables and absolute and relative frequencies for qualitative variables.
Second, the clinical characteristics of the European and Ibero-American populations were compared. The chi-square test or Fisher exact test was used to compare categorical variables, and the t test was used to compare quantitative variables.
To evaluate whether the clinical differences between the 2 populations were explained by the prevalence of HLA-B27, the patients were divided into HLA-B27–positive and HLA-B27–negative groups. Thus, European and Ibero-American populations were compared within the HLA-B27 subgroups in terms of clinical and sociodemographic characteristics. Multivariate analyses were also conducted in HLA-B27–positive and HLA-B27–negative populations to evaluate disease characteristics that are independently associated with the European and Ibero-American populations by using variables with P < 0.20 from the univariate analysis. These 2 multivariate analyses were adjusted for the time since symptom onset and the use of biologic drugs, since they may influence the clinical characteristics of the disease. The backward stepwise method was employed, and the presence of confounding and interacting factors was evaluated.
Subsequently, the overall population was stratified by race (White, Black American, and American Indian) to assess the clinical characteristics associated with each race. Comparisons were made by using chi-square or Fisher exact tests for categorical variables and ANOVA or the Mann-Whitney U test for continuous variables.
The hypothesis tests were 2-tailed, and P < 0.05 was considered to indicate statistical significance. The data were collected, processed, and analyzed by using IBM SPSS Statistics version 25 (IBM).
RESULTS
European patients vs Ibero-American patients. The demographic and clinical characteristics of European patients and Ibero-American patients are described in Table 1.
Comparison of the clinical and demographic characteristics between European and Ibero-American patients with r-axSpA according to the presence of HLA-B27.
A total of 2592 patients with a clinical diagnosis of r-axSpA were included in the analysis, comprising 1083 (41.8%) Ibero-American patients and 1509 (58.2%) European patients. Significant differences were observed in several variables between the 2 groups. Among patients from Ibero-America, we found a greater prevalence of smoking (21.4% vs 8.5%) and previous gastrointestinal (GI) or urogenital infections (3.7% vs 0.7%; Table 1). HLA-B27 was less prevalent in Ibero-American patients than in European patients (71.4% vs 83.4%). Higher and more significant prevalences of asymmetric or lower limb arthritis (57.2% vs 33.2%), enthesitis (54.5% vs 30.7%), and dactylitis (11.7% vs 5.3%) were also found in Ibero-American patients compared to European patients, whereas radiographic sacroiliitis was less frequent (91.4% vs 95.1%). Moreover, Ibero-Americans used more csDMARDs (59.2% vs 21.8%) and had more structural damage according to the BASRI (8.4 [SD 4.0] vs 7.3 [SD 3.9]).
European vs Ibero-American patients according to HLA-B27 status. The demographic and clinical characteristics of the 2 populations included in the study (Europeans and Ibero-Americans) according to the presence of HLA-B27 are described in Table 1.
• HLA-B27 positivity. A total of 1499 patients were HLA-B27 positive, 407 (27.2%) of whom were Ibero-Americans and 1092 (72.8%) of whom were Europeans. Among the HLA-B27–positive patients, those who were Ibero-Americans were younger (40.0 [SD 19.3] yrs vs 47.8 [SD 12.7] yrs), had a shorter delay in diagnosis (5.8 [SD 7.2] yrs vs 7.7 [SD 9.1] yrs), were less frequently unable to work (11% vs 24.5%), and smoked more (20.2% vs 8.5%) than Europeans. Among HLA-B27–positive patients, Ibero-Americans had more peripheral manifestations (asymmetric or lower limb arthritis [53.9% vs 32.2%], enthesitis [47.5% vs 30%], and dactylitis [7.9% vs 3.8%]), and less alternating buttock pain (59.7% vs 66%), with a greater prevalence of previous GI and genitourinary infections (3.2% vs 0.7%) than the European population. In terms of treatments, they used more csDMARDs (63.6% vs 19%), and they also had more loss of functionality (BASFI 4.7 [SD 2.9] vs 3.8 [SD 2.6]) and more structural damage (BASRI 8.3 [SD 4.0] vs 7.2 [SD 3.9]), than Europeans.
The results of the multivariate analysis of the factors independently associated with the Ibero-American patients after adjustment for bDMARD intake and time since symptom onset are presented in Figure 1 and Figure 2. Among patients who were HLA-B27 positive, Ibero-American status was independently associated with university education (OR 4.36, 95% CI 1.83-10.43), csDMARD intake (OR 4.21, 95% CI 2.02-8.80), asymmetric or lower limb arthritis (OR 2.33, 95% CI 1.16-4.86), enthesitis (OR 6.01, 95% CI 2.81-12.85), dactylitis (OR 6.10, 95% CI 2.11-17.60), worse structural damage according to the total BASRI (OR 1.12, 95% CI 1.00-1.24), and worse functionality according to the BASFI (OR 1.40, 95% CI 1.17-1.68; Figure 1A). Interestingly, a longer delay in diagnosis, greater use of csDMARDs, and less use of bDMARDs were associated with Ibero-American patients in the multivariate analysis.
Factors associated with Ibero-American countries vs European countries in (A) HLA-B27–positive patients and (B) HLA-B27–negative patients. ASDAS: Axial Spondyloarthritis Disease Activity Score; BASFI: Bath Ankylosing Spondylitis Functional Index; BASRI: Bath Ankylosing Spondylitis Radiological Index; bDMARD: biologic DMARD; csDMARD: conventional synthetic DMARD; DMARD: disease-modifying antirheumatic drug.
Clinical expression of r-axSpA and its association with HLA-B27 in European and Ibero-American populations: data from the REGISPONSER and RESPONDIA registries. ASDAS: Axial Spondyloarthritis Disease Activity Score; BASFI: Bath Ankylosing Spondylitis Functional Index; BASRI: Bath Ankylosing Spondylitis Radiological Index; bDMARD: biologic DMARD; csDMARD: conventional synthetic DMARD; DMARD: disease-modifying antirheumatic drug; r-axSpA: radiographic axial spondyloarthritis; REGISPONSER: Registry of Spondyloarthritis of Spanish Rheumatology; RESPONDIA: Ibero-American Registry of Spondyloarthropathies.
• HLA-B27 negativity. A total of 380 patients were HLA-B27 negative, 163 (42.9%) of whom were Ibero-Americans and 217 (57.1%) of whom were Europeans. We found similar differences to those previously described, with greater peripheral manifestations (such as asymmetric or lower limb arthritis, enthesitis, and dactylitis) in Ibero-American patients. We also found a higher prevalence of previous infections, although the differences were not significant. Among HLA-B27–negative patients, Ibero-American patients used bDMARDs less frequently (3.2% vs 19.5%) but csDMARDs more frequently (78.7% vs 28.6%) than Europeans.
Multivariate analysis of HLA-B27-negative patients demonstrated that Ibero-Americans were independently associated with enthesitis (OR 11.67, 95% CI 3.69-36.84), csDMARDs (OR 15.51, 95% CI 4.13-58.23), and total BASRI (OR 1.34, 95% CI 1.11-1.62) after adjusting for time since symptom onset and bDMARD use (Figure 1B).
Differences across races. Of the 1950 patients with available data for race, 1502 (77%) were White, 220 (8.5%) were Black American, and 228 (11.7%) were American Indian.
A description of the demographic and clinical characteristics of the 3 races (White race vs Black American race vs American Indian race) is provided in Table 2.
Comparison of the clinical and demographic characteristics of White vs Black American vs American Indian patients with r-axSpA (N = 1950).
Analysis of clinical characteristics demonstrated some disparities based on racial categories. On average, White patients were older than Black American and American Indian patients, as well as had a longer time since diagnosis (12.3 yrs vs 5.6 yrs vs 6.5 yrs for White, Black American, and American Indian patients, respectively). The smoking prevalence was highest among American Indian patients (20.2%), followed by Black American patients (16.7%) and White patients (15%).
Clinical manifestations also varied across racial groups, with differences noted in the prevalence of peripheral joint manifestations, such as increased incidences of arthritis and enthesitis in the American Indian population compared with White and Black American patients. PsO was more prevalent in the White patient group (10.8%), followed by the American Indian population (7.1%), and the Black American population (5%).
Laboratory variables such as HLA-B27 positivity also significantly differed among the groups. There was a greater percentage of HLA-B27 positivity in White patients (82.3%) than in American Indian patients (56.8%) and Black American patients (68.9%). Treatment patterns varied, with Black American (64.3%) and American Indian patients (55.3%) showing higher utilization rates of csDMARDs than White patients (29.8%). In contrast, White individuals used more bDMARDs (18.9%) than Black American (10%) and American Indian patients (9.6%).
The demographic and clinical characteristics of the 3 races (White vs Black American vs American Indian) according to HLA-B27 status are described in Table 3.
Comparison of the clinical and demographic characteristics of White vs Black American vs American Indian patients with r-axSpA according to the presence of HLA-B27.
A total of 1062 patients were HLA-B27 positive, of which 915 (86.2%) were White, 93 (8.8%) were Black American, and 54 (5.1%) were American Indian. In contrast, a total of 280 patients were HLA-B27 negative, of which 197 (70.4%) were White, 42 (15%) were Black American, and 41 (14.6%) were American Indian. In both the HLA-B27–positive and HLA-B27–negative groups, White individuals had the lowest prevalence of arthritis in comparison with Black Americans and American Indians, whereas American Indians had the lowest prevalence of sacroiliitis in both groups.
DISCUSSION
In this study, we provide new data on the clinical differences between Ibero-American and European populations with r-axSpA after considering HLA-B27 status. We found that in our study, Ibero-American patients with r-axSpA exhibit more peripheral manifestations, greater structural damage, and worse functionality than patients from Europe, regardless of the presence of HLA-B27. These results suggest that the low prevalence of HLA-B27 in Ibero-American patients is not the sole reason for this predominant peripheral phenotype, as other environmental and genetic factors may be involved in these differences.
This comparative analysis of European and Ibero-American patients with r-axSpA provides information about the complex interplay of genetic, demographic, and clinical factors influencing disease manifestation and management. Our results agree with previous studies highlighting the heterogeneous nature of SpA across different populations and the need for tailored therapeutic approaches and improved diagnostic strategies.28,6
In our study, we observed some disparities in demographic characteristics that may have influenced the results, such as the prevalence of smokers and university-educated individuals. We have observed that Europeans consume less tobacco, which is a factor that, in previous studies, has been associated with a lower incidence of peripheral manifestations and a paradoxical protective effect.29,30 Another disparity to highlight is the differences observed in the prevalence of university education, with higher rates in Ibero-American countries, which is possibly a result of differences in healthcare infrastructure. In Ibero-America, access to healthcare may be influenced by one’s ability to afford private healthcare (eg, patients with a higher educational level may better be able to afford such costs), whereas in Spain and Portugal, healthcare is free and publicly available.
The pronounced discrepancy in HLA-B27 positivity between European and Ibero-American cohorts aligns with previous literature emphasizing the strong genetic predisposition conferred by this antigen in patients with axSpA.31 Numerous studies have underscored the significant role of HLA-B27 in disease susceptibility and phenotype heterogeneity, with prevalence rates varying widely across racial and ethnic groups.32 Our observations corroborate prior evidence suggesting a greater prevalence of HLA-B27 positivity among European patients with r-axSpA than among Ibero-American patients.33,34,9 To prevent the discrepancies that were observed between the 2 groups from being influenced by the presence of HLA-B27, we divided the groups according to the presence of this antigen.
The distinct clinical manifestations noted between the European and Ibero-American cohorts underscore the multifaceted nature of r-axSpA. Although European patients exhibit a lower prevalence of peripheral manifestations such as enthesitis and dactylitis, they report a greater frequency of alternating buttock pain. These results are in conjunction with those of previous studies, in which we observed a greater incidence of peripheral manifestations in patients from Latin America.6,7 Based on previous studies, this scenario could be because of a lower prevalence of HLA-B27 in these countries11-14; however, in our study, we observed that peripheral manifestations are still present regardless of the presence of HLA-B27. These observations may reflect underlying differences in disease phenotype and severity, which may be influenced by genetic, environmental, and sociodemographic factors or other factors, such as the microbiome.35
The observed disparity in the prevalence of genitourinary or GI infections between the 2 groups, regardless of the presence of HLA-B27, could be explained by environmental factors and hygiene practices across regions. Ibero-American countries may face challenges related to sanitation infrastructure and cultural norms surrounding hygiene practices, which could contribute to higher rates of infection in these patients than in European patients. The higher incidence of infections in Ibero-American countries may also contribute to the increased burden of arthritis in these regions.
In relation to the treatments used, Ibero-American patients were more frequently treated with csDMARDs than European patients, which has already been described in previous studies.6,8 This may be because of the greater prevalence of peripheral manifestations in these patients. Notably, biologics are less commonly used in Ibero-American countries than in European countries.
Structural damage was more common in Ibero-American countries than in European countries, despite a shorter time since symptom onset and diagnosis delay in the former, as well as no differences in disease activity. Genetic factors may play a role in disease pathogenesis and progression in these patients. These differences were maintained regardless of the presence of HLA-B27, although in the group of patients who were negative for HLA-B27, these differences were not statistically significant. Additionally, we observed a greater loss of functionality in patients from Ibero-American countries, which was possibly a result of greater structural damage.
Our analysis also demonstrated significant racial disparities in disease presentation among patients with r-axSpA. When considering demographic factors, the prevalence of smoking varied significantly among racial groups, with American Indian patients demonstrating the highest rates. Education level emerged as another differentiating factor, with Black American patients showing a greater proportion having undertaken university studies. This could be because of the limitations of accessing private healthcare for patients with fewer resources in countries with a lower socioeconomic level, as we have previously discussed. Similarly, variations in inability-to-work rates indicate potential disparities in work-related disability and access to supportive services.
Regarding the disease phenotype according to race, American Indian patients had a greater prevalence of peripheral manifestations, followed by Black American patients. Although HLA-B27–positive Black American patients demonstrated a greater incidence of arthritis than White and American Indian patients, American Indian patients exhibited a greater prevalence of arthritis in the HLA-B27–negative group. The prevalence of enthesitis was greater in the American Indian group, despite the increased presence of HLA-B27. A greater presence of peripheral manifestations has been observed in Black Americans compared to White individuals in previous literature,33 although, to our knowledge, no studies have compared the prevalence of peripheral manifestations in Black Americans with that in American Indian individuals.
A greater prevalence of PsO has been observed in White patients, which is consistent with findings from previous studies.36,37,38 These differences are maintained if we take into consideration HLA-B27 status. In terms of uveitis incidence, it was greater in American Indian patients than in patients in other racial groups. These differences are maintained regardless of the presence of HLA-B27.
In terms of treatment, Black American and American Indian patients were more likely to use csDMARDs than White patients, which is likely because of the greater presence of peripheral manifestations. Conversely, White patients were more commonly treated with biologic therapy in our study, regardless of HLA-B27 status, which is perhaps because of the often higher socioeconomic status of these patients.
When comparing the 3 races, Black American patients had a higher ESR and greater loss of functionality (according to the BASFI), which is consistent with results from a previous study.39 The differences in the ESR persisted even when we distinguished the groups by the presence of HLA-B27; moreover, worse functionality was observed in these patients. In our study, we observed greater structural damage in American Indian patients than in Black American and White patients. Among the factors that could cause greater loss of functionality and structural damage in Black American and American Indian patients, genetic factors or lower use of biologic therapies compared to White patients could be identified.
These findings highlight the importance of considering racial factors in the diagnosis and management of the disease, as they may influence disease severity and treatment response.
Our study had several limitations and strengths. One limitation was the cross-sectional nature of the registry and the inability to make causal assumptions. Further, the groups were not homogeneous in terms of race, with the White race being the most common. Future research efforts should be conducted to address these limitations through prospective, multicenter studies incorporating comprehensive clinical and genetic profiling to elucidate the underlying mechanisms driving regional disparities in patients with r-axSpA. Another limitation of this study is the antiquity of the cohort, as the data were collected between 2004 and 2007 for the REGISPONSER registry and between 2006 and 2007 for the RESPONDIA registry. Because of this, there may be an overrepresentation of HLA-B27–positive cases. During the time of data collection, HLA-B27 testing was commonly used to confirm the diagnosis of SpA because magnetic resonance imaging had not yet been introduced as a diagnostic tool, and this could have led to a higher proportion of HLA-B27–positive patients being included in the registries. One aspect to highlight related to this is that only patients with r-axSpA were included, and this could have excluded patients in earlier disease stages or those with nonradiographic forms of axSpA. We note that this approach, although limiting, ensures a more homogeneous study population for comparison. One strength of this study was the large number of patients and the representation of the whole spectrum of patients with r-axSpA because of the combination of both registries (RESPONDIA and REGISPONSER). Another strength of this study involved the evaluation of the clinical differences across races in patients with r-axSpA, which has not been intensively studied previously.
Our study highlights the importance of tailored therapeutic strategies and culturally sensitive healthcare approaches for addressing the diverse needs of patients with r-axSpA across different regions. Clinicians should remain vigilant to regional variations in disease presentation, genetic predisposition, and treatment response, thus advocating for personalized care pathways informed by an understanding of patient demographics and clinical phenotypes. In the future, collaborative efforts among researchers, clinicians, and policymakers are essential to optimize patient outcomes and mitigate disparities in care delivery on a global scale.
In conclusion, our study highlights the complex interplay of demographic, racial, and socioeconomic factors in the presentation and management of patients with r-axSpA. Compared with patients from Europe, the Ibero-American patients with r-axSpA in our study exhibited more peripheral manifestations, more structural damage, and worse functionality, regardless of the presence of HLA-B27. Along with American Indian patients, Black American patients had a greater prevalence of peripheral manifestations and a greater loss of functionality regardless of HLA-B27 positivity.
ACKNOWLEDGMENT
The authors would like to thank all the investigators from the REGISPONSER and RESPONDIA study groups. REGISPONSER: P. Zarco-Montejo, Hospital Fundación Alcorcón, Madrid; C. González, Hospital Gregorio Marañón, Madrid; J. Mulero-Mendoza, Hospital Puerta de Hierro, Madrid; J.L. Fernández-Sueiro, Hospital Juan Canalejo, La Coruña; R. Almodóvar, Hospital Fundación Alcorcón, Madrid; C. Montilla, Hospital Virgen de la Vega, Salamanca; E. Moreno, Hospital San Rafael, Barcelona; A. Juan-Mas, Hospital Fundación Son Llatzer, Mallorca; P. Fernández-Dapica, Hospital 12 de Octubre, Madrid; M.C. Fernández-Espartero, Hospital de Móstoles, Madrid; V. Villaverde, Hospital de Móstoles, Madrid; M.E. Brito-Brito, Hospital Universitario Ramón y Cajal, Madrid; J.C. Torre-Alonso, Hospital Monte Naranco, Oviedo; E. Batlle-Gualda, Hospital General Universitario, Alicante; E. Cuende-Quintana, Hospital Universitario Príncipe de Asturias, Madrid; T. Clavaguera-Poch, Hospital de Palmaos, Girona; M. Fernández-Prada, Hospital Universitario de Guadalajara, Guadalajara; and E. Judez-Navarro, Hospital Virgen del Perpetuo Socorro, Albacete. RESPONDIA: A. Alvarellos, Hospital Privado de Córdoba, Córdoba, Argentina; C. Asnal, Hospital Alemán, Buenos Aires, Argentina; J.C. Barreira, Hospital Británico, Buenos Aires, Argentina; A.G. Bernard Medina, Hospital F. Antonio Alcalde, Guadalajara, México; M.B. Bertolo, Universidade Campinas, Brazil; W.A. Bianchi, Santa Casa do Rio de Janeiro, Brazil; R. Bonfiglioli, Pontifícia Universidade Católica de Campinas, Brazil; S. Carneiro, Universidade Federal do Rio de Janeiro, Brazil; H.M.S. Carvalho, Hospital de Base, Brasília, Brazil; G.C. Casado, Hospital Militar Central, Buenos Aires, Argentina; J. Casasola Vargas, Hospital General de México, México City, México; F.A. Castro da Rocha, Universidade Federal do Ceará, Fortaleza, Brazil; R.L. Chacón, Policlínica Méndez Gimón, Caracas, Venezuela; I.P. Costa, Universidade Federal do Mato Grosso do Sul, Campo Grande, Brazil; A.P. Duarte, Universidade Federal de Pernambuco, Recife, Brazil; J. Espinoza-Villalpando, Hospital Regional PEMEX, Reynosa, México; M.H. Esteva, Hospital Central San Cristóbal, San Cristóbal, Táchira, Venezuela; C. Fuentealba, Hospital San Boraja Arriarán, Santiago, Chile; Y. Granados, Hospital Núñez Tovar, Maturín Monagas, Venezuela; G. Huerta-Sil, CLIDITER, México, México; M. Keiserman, Pontifícia Universidade Católica de Porto Alegre, Brazil; C.L. Kohem, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; N.H. Leite, Faculdade Souza Marques, Rio de Janeiro, Brazil; S.A.L. Lima, Hospital do Servidor Público Estadual de São Paulo, São Paulo, Brazil; E.S. Meirelles, Universidade de São Paulo, Brazil; R. Menin, Faculdade de Medicina de São José do Rio Preto, Brazil; O. Neira, Hospital del Salvador, Santiago, Chile; S. Paira, Hospital JM Cullen, Santa Fé, Argentina; F. Pimentel, Complexo Hospitalar Egas Moniz, Lisbon, Portugal; M. Pinheiro, Universidade Federal de São Paulo, Brazil; E. Polito, Santa Casa de Belo Horizonte, Brazil; G. Resende, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; S.L.E. Ribeiro, Universidade Federal do Amazonas, Manaus, Brazil; O.L. Rillo, Hospital Tornú, Buenos Aires, Argentina; M.B. Santiago, Escola de Saúde Pública da Bahia, Salvador, Brazil; H. Santos H, Instituto Portugués de Reumatología, Lisbon, Portugal; H. Scherbarth H, Mar del Plata, Argentina; M.F.L.C. Sauma, Universidade Federal do Pará, Belém, Brazil; T.L. Skare, Hospital Evangélico de Curitiba, Brazil; E. Sousa, Centro Hospitalar Lisboa Norte, Lisbon, Portugal; E. Spangenberg, Instituto Nacional de Reumatología, Montevideo, Uruguay; V. Valin, Universidade Federal do Espírito Santo, Vitória, Brazil; C. Vera, Hospital Luis Vernaza, Guayaquil, Ecuador; U. Verdejo, Hospital Carlos van Buren, Valparaíso, Chile; W.P. Vieira, Hospital Geral de Fortaleza, Brazil; R. Wong, S. Plaza, Rosario, Argentina.
The researchers listed in the acknowledgments section contributed to the recruitment of patients but did not actively participate in the writing or analysis of the manuscript.
Footnotes
CONTRIBUTIONS
MAPL: conceptualization, methodology, writing – original draft. LLP: data curation, investigation, writing – review & editing. PFU: formal analysis, visualization, writing – review & editing. RBV: investigation, resources, writing – review & editing. PSB: investigation, resources, writing – review & editing. JMC: investigation, resources, writing – review & editing. AB: investigation, resources, writing – review & editing. JG: conceptualization, methodology, writing – review & editing. XJ: investigation, resources, writing – review & editing. AEC: supervision, visualization, writing – review & editing. JVM: investigation, resources, writing – review & editing. IAR: software, investigation, writing – review & editing. ECE: conceptualization, methodology, supervision, original draft, supervision. CLM: conceptualization, methodology, writing – original draft, supervision.
FUNDING
This study was partially funded by the SER-GRESSER/JANSSEN grant, with no involvement from Janssen in its development.
COMPETING INTERESTS
The authors declare no conflicts of interest relevant to this article.
ETHICS AND PATIENT CONSENT
This study was approved by the ethics committee (Comision de Ética e Investigacion Sanitarias) of the Reina Sofia University Hospital from Cordoba, Spain, on April 21, 2006. Consent to participate was obtained from all participants prior to the commencement of the study.
- Accepted for publication January 3, 2025.
- Copyright © 2025 by the Journal of Rheumatology
