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.

Background: Obese RA patients have higher disease activity scores (DAS). Previous research showed that obese RA patients have higher tender joint count (TJC) and VAS general health. However, it remains unclear whether DAS components measuring local and systemic inflammation (swollen joint count (SJC), CRP) are increased and if this is present in the total RA population or confined to an ACPA subgroup. As ACPA is suggested to enhance inflammatory responses, we hypothesized that the association of obesity with SJC and CRP is present especially in ACPA-positive RA. We therefore studied associations of obesity with courses of DAS components in ACPA subgroups.

Methods: We studied 649 RA patients (291 ACPA-positive), included in the Leiden Early Arthritis Clinic. Five-year courses of DAS44 and DAS44 components (SJC-44, TJC-53, CRP, VAS (0-100)) were compared between RA patients with normal weight (BMI 18.5-24.9), overweight (25.0-29.9), and obesity (≥ 30.0), stratified for ACPA. Linear/Poisson mixed models with a knot at 4 months were used.

Results: Obese RA patients had + 0.32 higher DAS compared to normal weight during the 5-year follow-up. In ACPA-positive RA, obese patients had + 0.43 (95% CI: 0.22, 0.64) higher DAS, whereas in ACPA-negative RA, this difference was smaller and not statistically significant: + 0.19 (95% CI: - 0.01, 0.38). In ACPA-positive RA, all DAS components were significantly higher in obese patients compared to normal weight: SJC + 60% (IRR1.60; 95% CI: 1.18, 2.16), CRP + 3.7 mg/L (95% CI:0.95, 6.53), TJC + 55% (IRR1.55; 95% CI:1.15, 2.10), and VAS + 9 (95% CI: 4.0, 14.2). ACPA-negative obese RA patients tended to have higher TJC (IRR1.22; 95% CI: 0.96, 1.55) and VAS (β4.3; 95% CI: - 0.4, 9.0), while SJC (IRR1.07; 95% CI:0.85, 1.33) and CRP (β0.24; 95% CI: - 1.29, 3.32) were unaffected.

Conclusion: The association of obesity with a worse DAS course is mainly present in ACPA-positive RA; especially SJC and CRP levels remain higher in ACPA-positive RA patients with obesity but not ACPA-negative RA patients. This is the first demonstration that obesity influences the disease course of ACPA-positive and ACPA-negative RA differently.