Vela-Casasempere Paloma, Otero-Varela Lucía, Gómez Sabater Silvia, Caño Alameda Rocío, Campos Fernández Cristina, Calvo-Gutiérrez Jerusalén, Pérez-Vera Yanira, Arija Sara Manrique, Bustabad Sagrario, Manero Ruiz Javier, Ruiz Montesino María Dolores, Ruíz Gutiérrez Lucía, Mera Varela Antonio, Moreno Ramos Manuel José, Sánchez-Alonso Fernando, Castrejón Isabel
Balmis General University Hospital, Miguel Hernández University, Spain, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain.
Research Unit, Spanish Society of Rheumatology, Spain, Autonomous University of Madrid Doctoral School, Madrid, Spain.
Arthritis Res Ther. 2025 May 14;27(1):103. doi: 10.1186/s13075-025-03571-2.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that can lead to progressive joint damage and irreversible disability when inadequately treated. RA is more common in women than in men. Disease characteristics differ between genders in terms of comorbidities, extra-articular manifestations, quality of life, disease activity and functional scores. There is a possibility that RA may be managed differently depending on gender: under-treated due to professional bias when prescribing advanced therapies, or over-treated due to overestimation of disease activity. Our primary objective was therefore to examine gender differences in the time course from RA diagnosis to initiation of the first biologic disease-modifying antirheumatic drug (bDMARD) or targeted synthetic DMARD (tsDMARD) and to identify factors associated with earlier or later prescribing. We also aimed to assess the differences between men and women in clinical characteristics and disease activity at initiation of the first b/tsDMARD among bio-naïve RA patients.
We analyzed RA patients from the BIOBADASER III registry who began their first b/tsDMARD between 2000 and 2023, stratified by treatment start year. Clinical characteristics were compared by sex, using linear regression models for DAS28. Kaplan-Meier curves and multivariate Cox regression identified factors influencing treatment initiation timelines.
We included 3,384 patients (78.1% women). Males presented higher cardiovascular risk, females more osteoporosis and Sjögren Syndrome. At treatment start, females had lower mean age (54.8 vs. 57 years, p < 0.001) but longer disease duration (7.3 vs. 6.7 years, p = 0.031); higher DAS28-ESR, but not DAS28-CRP; higher subjective components of DAS28 and ESR but lower CRP and no differences in objective components. Disease duration differed between sexes only in the most recent cohort (≥ 2017, HR 0.9 (95% CI 0.81; 0.99), p = 0.026): female sex, age, and treatment with csDMARDs (other than methotrexate) were associated with later prescribing, whereas tobacco, obesity and treatment with methotrexate or glucocorticoids with earlier.
Later prescribing in women despite higher activity rates merits reflection. Discrepancies between subjective and objective measures of DAS, and ESR and CRP, may reflect the need to establish different cut-off points for men and women, and opens a field of research worth exploring.
类风湿关节炎(RA)是一种慢性全身性炎症性自身免疫性疾病,若治疗不当可导致进行性关节损伤和不可逆残疾。RA在女性中比在男性中更常见。在合并症、关节外表现、生活质量、疾病活动度和功能评分方面,疾病特征存在性别差异。RA可能因性别而有不同的管理方式:在开具高级疗法时由于专业偏见而治疗不足,或由于对疾病活动度的高估而治疗过度。因此,我们的主要目标是研究从RA诊断到开始使用第一种生物性改善病情抗风湿药物(bDMARD)或靶向合成DMARD(tsDMARD)的时间过程中的性别差异,并确定与早期或晚期处方相关的因素。我们还旨在评估初治RA患者在开始使用第一种b/tsDMARD时男性和女性在临床特征和疾病活动度方面的差异。
我们分析了BIOBADASER III注册中心2000年至2023年间开始使用第一种b/tsDMARD的RA患者,并按治疗开始年份进行分层。通过性别比较临床特征,使用DAS28的线性回归模型。Kaplan-Meier曲线和多变量Cox回归确定了影响治疗开始时间的因素。
我们纳入了3384例患者(78.1%为女性)。男性有更高的心血管风险,女性有更多的骨质疏松症和干燥综合征。在开始治疗时,女性的平均年龄较低(54.8岁对57岁,p<0.001),但病程较长(7.3年对6.7年,p=0.031);DAS28-ESR较高,但DAS28-CRP不高;DAS28和ESR的主观成分较高,但CRP较低,客观成分无差异。仅在最近一组队列(≥2017年,HR 0.9(95%CI 0.81;0.99),p=0.026)中,性别间病程存在差异:女性、年龄以及使用传统合成改善病情抗风湿药物(csDMARDs,不包括甲氨蝶呤)与较晚处方相关,而吸烟、肥胖以及使用甲氨蝶呤或糖皮质激素与较早处方相关。
尽管女性疾病活动率较高但处方较晚,这值得反思。DAS、ESR和CRP主观与客观测量之间的差异,可能反映出需要为男性和女性建立不同的切点,并开辟了一个值得探索的研究领域。