Session Information
Date: Tuesday, November 10, 2015
Title: Rheumatoid Arthritis - Clinical Aspects IV: Biomarkers, Disease Progression and Treatment Response
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose:
The inflammatory cell infiltrate in RA synovium has been recognised to organise into lymphocytic aggregates (Ags) with data to suggest that these structures are immunologically competent and can support chronic inflammation. However, their clinical significance has been controversial with conflicting publications reporting diverse associations with disease outcome. Therefore the aim of this study was to determine whether synovial pathotypes associate with clinical phenotype and predict radiographic damage at 12 months in early RA.
Methods:
A cohort of 119 consecutive DMARD-naïve early RA patients (<12 months duration, 2010 ACR/EULAR criteria) were recruited as part of the MRC-funded Pathobiology of Early Arthritis Cohort (PEAC) http://www.peac-mrc.mds.qmul.ac.uk/at Barts and the London Hospital and underwent a pre-treatment baseline US-guided synovial biopsy. Baseline demographics (including ESR, CRP, RF, ACPA and DAS28) and US score (0-3, synovial thickness (ST) and power doppler (PD) of biopsied joint and 12-joint total US score (10 MCP and 2 wrist joints), at baseline were determined. Furthermore, baseline and 12 month hand/feet radiographs underwent Sharp/van der Heijde scoring (SHS). All patients were treated with DMARD combination therapy +/- oral steroids with a treat to target approach (DAS<2.6). Paraffin embedded sections of synovial tissue underwent routine immunohistochemical staining for CD20+ B cells and CD68+ macrophages. Patients were then categorised as aggregate (AG) if grade 2/3 CD20+ Ags were identified and following semi-quantitative scoring (0-4) for CD68+ sublining macrophages into pauciimmune (PI) (≤ 2 CD68+) or diffuse (D) (>2 CD68+, +/- grade 1 Ags). Finally significant differences in clinical parameters at baseline and progression in SHS (≥1) score at 12 months between the 3 synovial pathotypes was determined.
Results: (Table)
At baseline a significantly higher DAS28 score (p=0.02) was seen in the AG vs D or PI pathotype. The number of patients sero + for RF and ACPA was also significantly higher (p=0.029, 0.038) in the AG group. Furthermore US-ST and US-PD scores of the biopsied joint were significantly higher and a trend for higher total US-ST and US-PD scores was also seen in the AG group. Finally a significantly higher number of radiographic progressors were seen in the AG group (p=0.02).
Conclusion:
The significant association between synovial lymphocytic Ags and high disease activity/ sero positivity in patients with early RA suggests a critical role for these structures in RA pathogenesis. Furthermore in this cohort despite a treat to target approach patients with an AG pathotype were significantly more likely to develop progressive radiographic damage. Such data suggests the potential for early patient stratification in order to target effective therapies according to clinical need.
Table 1: Clinical, US and radiographic characteristics according to synovial pathotype
|
N=119 |
Synovial pathotype |
P value (Anova or Chi sq as appropriate) |
|||
|
Mean (SD) |
Pauciimmune (38) |
Diffuse (39) |
Aggregate (42) |
||
|
Age |
48.9 (14.0) |
51.6 (19.0) |
53.3 (17.7) |
0.52 |
|
|
Disease duration (months) |
5.3 (3.6) |
4.9 (2.5) |
5.6 (3.5) |
0.61 |
|
|
ESR (mm/hr) |
25.3 (28.5)) |
29.8 (21.2) |
52.1 (29.2) |
<0.0001 |
|
|
CRP (mg/l) |
11.5 (37.1) |
16.2 (21.9) |
23.6 (25.3) |
0.17 |
|
|
RF+/RF- |
25/13 |
22/17 |
35/7 |
0.029 |
|
|
ACPA+/- |
24/14 |
25/14 |
36/6 |
0.038 |
|
|
Swollen Joints |
6.7 (6.4) |
6.8 (4.7) |
8.2 (5.9) |
0.42 |
|
|
Tender Joints |
11.1 (7.9) |
9.8 (6.2) |
12.6 (7.2) |
0.20 |
|
|
VAS (mm) |
59.6 (27.0) |
59.1 (27.8) |
69.1 (21.7) |
0.14 |
|
|
DAS28 |
4.9 (1.7) |
5.3 (1.2) |
6.1 (1.5) |
0.02 |
|
|
HAQ |
1.4 (0.9) |
1.4 (0.7) |
1.6 (0.79) |
0.47 |
|
|
SHS (baseline) (n=104) |
1.9 (4.1) |
1.8 (4.1) |
4.7 (10.2) |
0.14 |
|
|
US biopsied joint (0-3) |
ST |
1.9 (0.8) |
2(0.77) |
2.73(0.45) |
<0.0001 |
|
PD |
1.2 (1) |
1.5 (0.98) |
2.3 (0.75) |
<0.0001 |
|
|
US total (12 joint, 0-36) |
ST |
14.8 (8.4) |
16.1 (8.9) |
16.8 (9.7) |
0.67 |
|
PD |
4.2 (5.3) |
6.4 (5.8) |
7.5 (6.6) |
0.08 |
|
|
Mean corticosteroid dose (mg) |
3.2 (3.2) |
4.4 (3.6) |
4.1 (2.7) |
0.26 |
|
|
Mean MTX dose (mg) |
11.2 (7.7) |
13.8 (7.4) |
13.8 (8.16) |
0.29 |
|
|
SHSS progressors/non progressors (n=88) |
2/26 |
2/27 |
9/22 |
0.021 |
|
To cite this abstract in AMA style:
DiCicco M, Humby F, Kelly S, Hands R, ng N, Mahto A, Lazarou I, Rocher V, Zou L, Bombardieri M, Buckley C, van der Helm- van Mil AHM, Landewé RBM, van der Heijde D, McInnes IB, Taylor PC, Pitzalis C. Synovial Lymphocytic Aggregates Associate with Highly Active RA and Predict Erosive Disease at 12 Months: Results from the Pathobiology of Early Arthritis Cohort [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/synovial-lymphocytic-aggregates-associate-with-highly-active-ra-and-predict-erosive-disease-at-12-months-results-from-the-pathobiology-of-early-arthritis-cohort/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/synovial-lymphocytic-aggregates-associate-with-highly-active-ra-and-predict-erosive-disease-at-12-months-results-from-the-pathobiology-of-early-arthritis-cohort/