Clinical characteristics and associated factors of difficult-to-treat rheumatoid arthritis: a cross-sectional study

This study aimed to describe the clinical characteristics and explore factors cross-sectionally associated with difficult-to-treat rheumatoid arthritis (D2T RA) in a Chinese population, providing evidence for characterizing the clinical phenotype and identifying current associated factors in a Chinese population.

A cross-sectional study was conducted, enrolling RA patients treated at the Rheumatology Department of Dongfang Hospital, Beijing University of Chinese Medicine, from September 2022 to September 2024. Based on the 2020 EULAR criteria, adapted in accordance with the 2021 Chinese consensus on refractory rheumatoid arthritis, patients were categorized into a D2T RA group (n = 61) and a conventional RA group (n = 182). An exploratory subsample (n = 6 per group) underwent plasma cytokine analysis via Luminex assay. Data on demographics, disease activity measures, laboratory inflammatory parameters, comorbidities, and medication use were collected. Plasma cytokine levels were measured using Luminex technology. Statistical analysis was performed using R software, and associated factors were analyzed via univariate and multivariate logistic regression.

Patients in the D2T RA group were significantly younger than those in the RA group (P = 0.009) and exhibited significantly higher values in swollen joint count, VAS pain score, DAS28-ESR, CDAI, and SDAI (all P < 0.05). The prevalence of osteoporosis was significantly higher in the D2T RA group (85.25% vs. 61.54%, P = 0.001), and the usage of JAK inhibitors was also notably elevated (85.25% vs. 1.10%, P = 0.027). Regarding inflammatory markers, except for elevated plateletcrit, no significant differences were observed in CRP, ESR, IL-6, or composite inflammation indices between groups. Exploratory cytokine analysis (n = 6 per group) showed that IL-6 and IL-17A levels were significantly elevated in the D2T RA group compared to healthy volunteers, whereas no significant differences were observed between the RA and D2T RA groups. Multivariate logistic regression identified that older age was associated with lower odds of D2T RA (OR = 0.94, 95% CI: 0.91-0.98, P =  0.011), while OP remained independently associated with higher odds (OR = 4.95, 95% CI: 1.96-12.15, P < 0.001).

In this single-center Chinese cohort, D2T RA was characterized by younger age, higher disease activity, and a higher comorbidity rate of osteoporosis. Younger age and comorbid osteoporosis were cross-sectionally associated with D2T RA. These findings may assist clinicians in recognizing high-risk clinical phenotypes and inform the development of targeted intervention strategies, but require confirmation in prospective, multicenter studies.