Obesity Linked to Increased Disease Activity in ACPA-Positive Rheumatoid Arthritis

Findings from a recent study suggest rheumatoid arthritis (RA) patients’ body mass index (BMI) may influence their disease activity, specifically in the case of anti-citrullinated protein autoantibody (ACPA)-positive RA.¹

Results showed worse disease activity scores (DAS), especially regarding elevated swollen joint count (SJC) and CRP, in patients with ACPA-positive RA and obesity but not ACPA-negative RA patients, suggesting obesity influences the disease course of ACPA-positive and ACPA-negative RA differently.¹

According to the US Centers for Disease Control and Prevention, being obese can increase the risk of developing RA. Additionally, a growing body of research has suggested disease outcomes and response to therapy may differ in patients with RA and obesity compared to patients who are normal-weight, including greater rates of chronic pain and elevated inflammatory markers.^2,3

“In addition to obesity, in vitro data suggested that auto-antibodies such as ACPA could also enhance inflammatory responses by increasing TNF-α production and complement system activation. This could contribute to the more severe disease course in ACPA-positive RA patients compared to ACPA-negative RA patients,” wrote investigators.¹ “However, it is unclear whether obesity affects disease activity, local and systemic inflammation similarly in ACPA-positive and ACPA-negative RA.”

To determine the effect of obesity on disease activity in relation to ACPA, Henk van Steenbergen, associate professor at the Cognitive Psychology unit at Leiden University, and colleagues examined patient data for Leiden Early Arthritis Clinic participants, a Netherlands population-based inception cohort consecutively including all newly presenting patients with recent onset arthritis ≥ 1 joint and a symptom duration < 2 years. Only patients with RA who were included from June 2011 onwards were assessed to ensure similar treatments and treatment strategies were used in all assessed patients.¹

In total, 649 patients with RA, 291 of whom were ACPA-positive, were included in the present study. At the first visit, patients and rheumatologists completed questionnaires, a physical examination was performed, and blood samples were taken for routine laboratory procedures.¹

Follow-up visits were performed at 4, 8, and 12 months during the first year and yearly thereafter. Follow-up ended in case of release from care due to prolonged sustained DMARD-free remission, withdrawal of informed consent while remaining treated, or death.¹

DAS44 was assessed at each visit and consisted of 4 components: SJC consisting of 44 joints (SJC-44), CRP, tender joint count (TJC) consisting of 53 joints (TJC-53), and visual analog scale general health (VAS). Investigators compared 5-year courses of DAS44 and DAS44 components between RA patients with normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), and obesity (≥ 30.0), stratified for ACPA.¹

Among the cohort, the mean age was 59.7 years, 63% of patients were female, the median BMI was 26.0, and the median DAS was 3.1. Investigators pointed out ACPA-positive patients had a lower median BMI (25.4 vs 26.4) and DAS (2.8 vs 3.3) compared to ACPA-negative patients.¹

Upon analysis, patients with obesity had a significantly greater DAS course compared to normal-weight patients. All DAS courses significantly decreased during follow-up, but patients with obesity had a 0.31 (95% CI, 0.17-0.45) higher DAS compared to normal-weight patients at diagnosis and during the entire follow-up.¹

In ACPA-positive RA, patients with obesity had a significantly higher DAS during the entire 5-year follow-up compared to normal weight patients (β0.43; 95% CI, 0.23-0.64), whereas in ACPA-negative RA, this difference was smaller and not statistically significant (β0.16; 95% CI; 0.03-0.36). Investigators pointed out the association between obesity and greater DAS scores in RA patients appeared to be predominantly present in ACPA-positive RA patients.¹

Additionally, patients with ACPA-positive RA and obesity had a significantly elevated SJC course compared to normal-weight patients (Incidence rate ratio [IRR], 1.59; 95% CI, 1.18-2.15). Of note, this association was not present in ACPA-negative patients with obesity.¹

Compared to ACPA-positive normal weight patients, ACPA-positive patients with obesity had 3.7 mg/L higher CRP levels at baseline and during 5-year follow-up (β3.7; 95% CI, 0.96-6.52). In ACPA-negative RA patients, however, CRP levels did not significantly differ for patients with overweight or obesity compared with normal weight patients (β0.17; 95% CI, 1.82-2.15 and β1.02; 95% CI, 1.29-3.33, respectively).¹

For TJC, investigators noted it was 56% higher in ACPA-positive RA patients with obesity compared to normal-weight patients (IRR, 1.56; 95% CI, 1.16-2.10). In ACPA-negative RA, a statistically non-significant trend towards an 18% higher TJC in patients with obesity was observed (IRR, 1.18; 95% CI, 0.93-1.50).¹

In ACPA-positive RA, both patients considered overweight (6; 95% CI, 2.5-10.2) and patients with obesity (9; 95% CI, 4.5-14.4) had significantly greater VAS scores compared to normal weight. In ACPA-negative RA, only RA patients with obesity had a trend towards an increased VAS (4; 95% CI, 0.8-8.5).¹

“In this large longitudinal study, we confirmed that patients with obesity tend to have a higher disease activity during the course of their disease compared to normal weight RA patients, and we identified that this adverse association is only present in ACPA-positive RA,” investigators concluded.¹

References:

1. ^{Hollander N.K.d., Boeren A.M.P., van der Helm-van Mil A.H.M. et al. Patients with obesity have more inflamed joints and higher CRP levels during the disease course in ACPA-positive RA but not in ACPA-negative RA. Arthritis Res Ther. https://doi.org/10.1186/s13075-023-03248-8}
2. ^{US Centers for Disease Control and Prevention. Rheumatoid Arthritis. Arthritis. April 7, 2022. Accessed February 14, 2024. https://www.cdc.gov/arthritis/types/rheumatoid-arthritis.html}
3. ^{Poudel D, George MD, Baker JF. The Impact of Obesity on Disease Activity and Treatment Response in Rheumatoid Arthritis. Curr Rheumatol Rep. 2020;22(9):56. doi:10.1007/s11926-020-00933-4}