Luciano Nicoletta, Barone Elisa, Brunetta Enrico, D'Isanto Alessio, De Santis Maria, Ceribelli Angela, Caprioli Marta, Guidelli Giacomo M, Renna Daniela, Selmi Carlo
Department of Biomedical Sciences, Humanitas University, Via R Levi Montalcini 4, Pieve Emanuele, Milan, 20090, Italy.
Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Via A Manzoni 56, Rozzano, Milan, 20089, Italy.
Arthritis Res Ther. 2025 Jan 3;27(1):2. doi: 10.1186/s13075-024-03432-4.
There is still a significant proportion of patients with rheumatoid arthritis (RA) in whom multiple therapeutic lines are ineffective. These cases are defined by the EULAR criteria as Difficult-to-Treat RA (D2T-RA) for which there is limited knowledge of predisposing factors.
To identify the clinical features associated with D2T-RA in real-life practice.
We retrospectively collected demographic, clinical, and serological data on 458 patients consecutively seen for RA between January 2019 and January 2023. We compared patients fulfilling the D2T-RA criteria with the remaining RA cohort using univariate comparisons and logistic regression to determine the impact of clinical features, comorbidities on outcome variable, adjusted for confounders.
Seventy-one/458 (16%) patients fulfilled the 2021 EULAR criteria for D2T-RA with no significant differences for age (median 62 years interquartile range -IQR- 58- 65 vs. 62 IQR 60 - 63 in non-D2T), gender prevalence (23% in both groups) and positivity rates for rheumatoid factors (62% vs. 62% in non-D2T) and Anti-Citrullinated Protein Antibodies (ACPA) (69% vs. 61% in non-D2T). Conversely, D2T-RA cases had significant longer disease duration (median 15 years IQR 13-17 vs. 10 years IQR 9-11 in non-D2T; p < 0.0001). D2T-RA also had more erosions at baseline (24% vs. 11% in non-D2T; p < 0.0001) and higher disease activity index (CDAI) at the last follow up visit (15.7 ± 10.5 vs. 7.5 ± 8.8 in non-D2T; p < 0.0001). D2T-RA cases suffered with higher frequency of obesity (33% vs. 19% in non-D2T, p = 0.021) and fibromyalgia (25% vs. 10% in non-D2T, p < 0.0001). The multivariate analysis confirmed the correlations of D2T-RA with disease duration (Odds ratio -OR- 1.06, 95% confidence interval -CI-1.03-1.09; p < 0.0001), baseline erosions (OR 2.73, 95% CI 1.28-5.82; p = 0.009), obesity (OR 2.22, 95% CI 1.10-4.50; p = 0.026) and fibromyalgia (OR 3.91, 95% CI 1.76-8.70; p = 0.001), independent of age and gender.
High disease activity, baseline erosions and disease duration are significantly associated with the D2T phenotype of RA while we confirm the importance of obesity and fibromyalgia.
类风湿关节炎（RA）患者中仍有相当比例的患者对多种治疗方案无效。根据欧洲抗风湿病联盟（EULAR）标准，这些病例被定义为难治性RA（D2T-RA），目前对其易感因素的了解有限。
确定实际临床中与D2T-RA相关的临床特征。
我们回顾性收集了2019年1月至2023年1月期间连续就诊的458例RA患者的人口统计学、临床和血清学数据。我们使用单因素比较和逻辑回归分析，比较符合D2T-RA标准的患者与其余RA队列，以确定临床特征、合并症对结局变量的影响，并对混杂因素进行校正。
458例患者中有71例（16%）符合2021年EULAR的D2T-RA标准，两组在年龄（中位数62岁，四分位间距-IQR-58-65岁，非D2T组为62岁，IQR 60-63岁）、性别患病率（两组均为23%）、类风湿因子阳性率（62% vs.非D2T组62%）和抗瓜氨酸化蛋白抗体（ACPA）阳性率（69% vs.非D2T组61%）方面无显著差异。相反，D2T-RA病例的病程显著更长（中位数15年，IQR 13-17年，非D2T组为10年，IQR 9-11年；p<0.0001）。D2T-RA在基线时也有更多的骨侵蚀（24% vs.非D2T组11%；p<0.0001），并且在最后一次随访时疾病活动指数（CDAI）更高（15.7±10.5 vs.非D2T组7.5±8.8；p<0.00
