Dataset Information

Differing time-orders of inflammation decrease between ACPA subsets in RA patients suggest differences in underlying inflammatory pathways.

ABSTRACT:

Objectives

Advanced imaging modalities have shown that not only joints but also bones and tendon sheaths can be inflamed at diagnosis of RA. We aimed to better understand the time-order in which the inflamed tissues respond to DMARD treatment. Also, because ACPA status may reflect a different pathophysiology, differences in time-order of inflammation decrease were hypothesized between these disease types.

Methods

A total of 216 consecutive patients presenting with RA (n = 176) or undifferentiated arthritis (n = 40), who all started with conventional synthetic DMARD treatment, were studied. 1.5T contrast-enhanced hand and foot MRIs were performed before treatment and after 4, 12 and 24 months. Cross-lagged models evaluated the influence of two time patterns: a simultaneous pattern ('change in one inflammatory feature associated with change in another feature') and a subsequent pattern ('change in one inflammatory feature preceded change in another feature'). ACPA stratification was performed.

Results

The median symptom duration at presentation was 13 weeks. Forty-four percent of patients was ACPA-positive. All pairs of inflammatory features decreased simultaneously in all time intervals (0-4/4-12/12-24 months; P < 0.05). Moreover, time-orders were identified: synovitis decrease preceded tenosynovitis decrease (0-4 to >4-12 months; P = 0.02 and 4-12 to >12-24 months; P = 0.03). Largely similar results were obtained in both ACPA subgroups. Additionally, in ACPA-positive but not ACPA-negative patients, synovitis decrease preceded osteitis decrease (4-12 to >12-24 moths; P = 0.002).

Conclusion

This study increased the understanding of the response to treatment on the tissue level. In addition to simultaneous decrease of inflammation, synovitis decrease preceded tenosynovitis decrease. Differences in time-order of inflammation decrease between ACPA subgroups suggest differences in underlying inflammatory pathways.

SUBMITTER: Matthijssen XME

PROVIDER: S-EPMC8213431 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundObese 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.MethodsWe 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.ResultsObese 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.ConclusionThe 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.