Obesity and fibromyalgia are associated with Difficult-to-Treat Rheumatoid Arthritis (D2T-RA) independent of age and gender.

Background: 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.

Objective: To identify the clinical features associated with D2T-RA in real-life practice.

Methods: 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.

Results: 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.

Conclusions: 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.