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

Lara D. Veeken, vol. 60, pp. 2969–2975

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.

Authors 4

1. X. Matthijssen corresponding Aachen Department of Rheumatology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands

2. Ellis Niemantsverdriet Aachen Department of Rheumatology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands

3. Saskia le Cessie Aachen Department of Biomedical Data Science Department of Epidemiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Biomedical Data Science, Leiden University Medical Center, Leiden, The Netherlands

   Department of Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

4. Annette H M van der Helm–van Mil Aachen Department of Rheumatology, Leiden University Medical Center

   Leiden University Medical Center · Erasmus MC

   Affiliation as printed

   Department of Rheumatology, Erasmus Medical Center, Rotterdam, The Netherlands

   Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands