Fibromyalgia, Obesity Linked to Difficult-to-Treat RA

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Research published in Arthritis Research & Therapy revealed the factors associated with difficult-to-treat rheumatoid arthritis (D2T-RA) include obesity, fibromyalgia, high disease activity, baseline erosions and longer disease duration. Investigators believe these results highlight the need for tailored strategies to manage this challenging subset of RA.

D2T-RA is estimated to affect between 5% and 20% of patients with RA. Although the criteria for D2T-RA — a subset that affects patients with disease that fails multiple therapies — is well defined, risk factors for developing the condition are not well understood.

“It is crucial to define how comorbidities can influence the clinical picture of patients with RA, particularly associating to D2T cases,” wrote lead investigator Nicoletta Luciano, M.D., assistant professor in rheumatology at Humanitas University in Milan, Italy.

To identify these clinical features and predisposing factors in real-life practice to improve the understanding and management of this condition, investigators performed a retrospective analysis of 458 patients with RA who visited the Rheumatology Outpatient Clinic at Humanitas Research Hospital in Milan between January 2019 and January 2023.

People who met the criteria for D2T-RA were compared with others to evaluate the demographic, clinical and serological factors. Relevant comorbidities included in the assessment were obesity, fibromyalgia, neuropsychiatric syndromes, cardiovascular diseases and diabetes.

Within the total cohort, 16% met the criteria for D2T-RA. No significant differences in age (median 62 years), gender (77% female in both cohorts), rheumatoid factor (RF) positivity or anti-citrullinated protein antibody (ACPA) positivity were observed between groups. RA was difficult to manage in 82% of patients in the D2T-RA group, according to their doctors.

Results showed patients with a longer disease duration (median 15 years compared with 10 years) were more likely to develop D2T-RA. Additionally, patients with D2T-RA had a higher prevalence of baseline erosions (24% versus 11%, respectively). This group also had greater disease activity, as measured by the Clinical Disease Activity Index (CDAI; 15.7 versus 7.5, respectively).

Comorbidities also influenced the safety and efficacy of treatment for RA. The D2T-RA cohort exhibited a greater prevalence of obesity (33% versus 19%, respectively) and fibromyalgia (25% versus 10%, respectively). Investigators encouraged nonpharmacological treatment methods for patients with D2T-RA, including regular psychologist and physiotherapist evaluations. Additionally, previous research has touted the benefits of weight loss programs on pain control, disease activity and physical functioning among patients with D2T-RA and obesity.

The multivariate analysis confirmed disease duration, baseline erosions, fibromyalgia and obesity were associated with this challenging condition, independent of age and gender.

Investigators viewed the real-world setting using data from a single tertiary center with a standardized approach to care as a strength of the study. However, the retrospective study design was a limitation. Additionally, they did not include certain variables, such as adherence to treatment and socioeconomic status, which could be linked to a higher risk of D2T-RA. The patients’ experience of their condition was also not included. Although fibromyalgia was diagnosed using the latest classification criteria, investigators said the clinical features and pathophysiology may be different among those with chronic conditions associated with pain. Finally, this study enrolled a heterogenous population of patients with high disease activity whose disease failed multiple drugs.

“Our explorative analysis suggests that further characterization is warranted to better phenotype patients with D2T-RA, particularly to understand the contribution of chronic inflammation, altered pain perception, and the role of both organic and psychological comorbidities in assessing disease activity and residual pain,” investigators concluded.