Background/Purpose: Cardiorenal-metabolic (CRM) therapies, such as SGLT-2 inhibitors and GLP-1 agonists, are medications that target interconnected pathways between cardiovascular, renal, and metabolic systems and may provide additional benefits for patients with rheumatoid arthritis (RA) by potentially reducing systemic inflammation. Our objectives were to (1) To assess the prevalence of CRM conditions and eligibility for CRM therapies based on approved indications and investigational (off-label) use in early RA (ERA). (2) To examine differences in clinical characteristics, including sex-based variations, for patients with and without CRM conditions.

Methods: Data were from the Canadian Early Arthritis Cohort, a cross-sectional study of patients recruited between 2017 and 2023, including baseline BMI, creatinine, Clinical Disease Activity Index (CDAI), and CDAI at 12 months. We estimated the baseline prevalence of approved Canadian CRM indications: (1) type 2 diabetes, (2) obesity (BMI ≥30 kg/m2), (3) heart failure, or (4) overweight (BMI ≥27 and < 30 kg/m2) + ≥ 1 weight-related complication of hypertension and/or dyslipidemia. Off-label indications included (5) chronic kidney disease (< eGFR < 60 mL/min/1.73 m2), (6) overweight BMI with elevated C-reactive protein (CRP >5mg/L), or (7) large joint osteoarthritis1. Descriptive statistics were done for the overall cohort. Stratification by sex was used to identify differences associated with CRM conditions.

Results: Out of 855 recruited patients, the final sample included 278 patients and 67% were female. The mean age was 57 ± 14 years, and mean symptom duration was 5.1 ± 2.7 months. At baseline, nearly all patients (90%) had moderate or high Clinical Disease Activity Index (CDAI) scores. Overall, 54% had one CRM condition and 45% met approved indications for CRM therapy, primarily for obesity (Table). Overlapping conditions increased (14% had ≥2 CRM) when off-label indications such as knee OA or overweight BMI + elevated CRP were considered. Patients with CRM conditions were older and had more non-metabolic comorbidities. However, there were no significant differences in disease activity components beyond inflammatory makers (mean CRP 9.5 mg/L vs. 4.8mg/L, p=0.01), nor were there differences in initial DMARD or corticosteroid strategies. In sex stratified analyses, no differences were observed between male and females for the number or type of CRM conditions (Table).

Conclusion: In this real-world ERA cohort, 45% of patients met criteria for approved CRM therapy, primarily for obesity and diabetes. Obesity is known to negatively affect RA disease activity and treatment response, making it a critical target for intervention. The lack of significant sex-based differences in CRM conditions further highlights the universal relevance of CRM conditions in RA management. Future research should explore how CRM therapies, particularly those targeting obesity, could improve metabolic health and RA outcomes, warranting their study in this population.Reference: 1. Bliddal H et al. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. N Engl J Med. 2024 Oct 31;391(17):1573-1583.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/exploring-the-potential-for-cardiorenal-metabolic-therapies-to-target-comorbidities-in-early-rheumatoid-arthritis/