Sex differences in axial spondyloarthritis: data from a Portuguese spondyloarthritis cohort

Authors

Rita Novais Cunha; Elsa Vieira-Sousa; Nikita Khmelinskii; Pedro Ávila-Ribeiro; Maura Couto; Maria Inês Seixas; Nádia Martins; Miguel Bernardes; Ana Martins; Ana Bento da Silva; Maria Helena Lourenço; Cláudia Miguel; Viviana Tavares; Paula Valente; José Costa; João Rovisco; Renata Aguiar; Vera Afreixo; Anabela Barcelos;

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Background: Axial spondyloarthritis (axSpA), particularly ankylosing spondylitis was historically considered a male’s disease and has been under-recognized in women. Emerging evidence reveals sex differences in pathophysiology, disease presentation and therapeutic efficacy. Objective: To identify differences between sexes in a Portuguese cohort of patients with axSpA regarding clinical manifestations, disease activity, functional capacity, patient related outcomes and presence of sacroiliitis on x-ray or magnetic resonance imaging. Methods: Patients with ≥18 years fulfilling the ASAS- Assessment of Spondyloarthritis International Society classification criteria for axSpA registered in the electronic Rheumatic Diseases Portuguese Register (Reuma.pt) were included in this multicentric cross-sectional study. Sociodemographic data, clinical features and imaging were collected from the first record in Reuma.pt. These variables were compared between sexes using Mann-Whitney test and Chi-Square test. Variables with a significant association with variable sex were considered in the multiple variable analysis to adjust the sex effect on the outcome variables. Statistical analysis was performed with R version 4.0.2 and p <0.05 was considered statistically significant. Results: A total of 1995 patients were included, 1114 (55.9%) men and 881 (44.1%) women. Men had an earlier disease onset (25.1 vs 28.4, p <0.001), were younger at diagnosis (26.9 vs 30.4, p<0.001) and were more frequently smokers (32.1% vs 15.7%, p <0.001). Comparing to women, men had worse Bath Ankylosing Spondylitis Metrological Index scores (4.0 vs 3.4, p<0.001), higher levels of C-Reactive Protein (10.5 vs 6.9 mg/L, p <0.001) and were more often Human Leukocyte Antigen-B27 positive (67.8% vs 54%, p <0.001). In contrast, women more frequently had inflammatory bowel disease (8.8% vs 4.9%, p =0.004), higher levels of erythrocyte sedimentation rate (25.0 vs 21.0mm/h, p=0.003) and worse patient-related outcomes- Bath Ankylosing Spondylitis Disease Activity Index (5.7 vs 4.5, p<0.001), Patient Global Assessment (60.0 vs 50.0, p <0.001) and fatigue (6.2 vs 5.0, p <0.001). Discussion: In this large multicentric study from a Portuguese axSpA cohort, we confirmed sex differences in patients with axSpA. This work brings awareness to these differences, resulting in less underdiagnosis and misdiagnosis, optimizing treatment strategies, and improving outcomes in axSpA.

Rita Novais Cunha
Serviço de Reumatologia, Centro Hospitalar do Baixo Vouga, Aveiro, Portugal

Elsa Vieira-Sousa
Serviço de Reumatologia, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte; Unidade de Investigação em Reumatologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Portugal

Nikita Khmelinskii
Serviço de Reumatologia, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte; Unidade de Investigação em Reumatologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Portugal

Pedro Ávila-Ribeiro
Serviço de Reumatologia, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte; Unidade de Investigação em Reumatologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Portugal

Maura Couto
Serviço de Reumatologia, Centro Hospitalar Tondela-Viseu, Viseu, Portugal

Maria Inês Seixas
Serviço de Reumatologia, Centro Hospitalar Tondela-Viseu, Viseu, Portugal

Nádia Martins
Serviço de Reumatologia, Centro Hospitalar Tondela-Viseu, Viseu, Portugal

Miguel Bernardes
Serviço de Reumatologia, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculdade de Medicina da Universidade do Porto, Departamento de Medicina e CINTESIS, Porto, Portugal

Ana Martins
Serviço de Reumatologia, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculdade de Medicina da Universidade do Porto, Departamento de Medicina e CINTESIS, Porto, Portugal

Ana Bento da Silva
Serviço de Reumatologia, CHLO - Hospital de Egas Moniz, Lisboa, Portugal; Comprehensive Health Research Center – CHRC, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School, Faculdade de Ciências Médicas, Lisboa, Portugal

Maria Helena Lourenço
Serviço de Reumatologia, CHLO - Hospital de Egas Moniz, Lisboa, Portugal; Comprehensive Health Research Center – CHRC, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School, Faculdade de Ciências Médicas, Lisboa, Portugal

Cláudia Miguel
Serviço de Reumatologia, Instituto Português de Reumatologia, Lisboa, Portugal

Viviana Tavares
Serviço de Reumatologia, Hospital Garcia de Orta, Almada, Portugal

Paula Valente
Serviço de Reumatologia, Centro Hospitalar Entre Douro e Vouga, Aveiro, Portugal

José Costa
Serviço de Reumatologia, Unidade Local de Saúde do Alto Minho, Ponte de Lima, Portugal

João Rovisco
Serviço de Reumatologia, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal; Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal

Renata Aguiar
Serviço de Reumatologia, Centro Hospitalar do Baixo Vouga, Aveiro, Portugal

Vera Afreixo
Department of Mathematics and CIDMA, Center for Research & Development in Mathematics and Applications, University of Aveiro, Portugal

Anabela Barcelos
Serviço de Reumatologia, Centro Hospitalar do Baixo Vouga, Aveiro, Portugal; Public Health Research Centre, NOVA National School of Public Health, Public Health Research Centre, Universidade NOVA de Lisboa, Portugal; Comprehensive Health Research Center

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