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Inclusion of fibrinoid necrosis increases the accuracy of synovial tissue assessment in predicting response to methotrexate: analysis of the UCLouvain Brussels ERA Cohort
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Inclusion of fibrinoid necrosis increases the accuracy of synovial tissue assessment in predicting response to methotrexate: analysis of the UCLouvain Brussels ERA Cohort
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Journal Article
Inclusion of fibrinoid necrosis increases the accuracy of synovial tissue assessment in predicting response to methotrexate: analysis of the UCLouvain Brussels ERA Cohort
2024
Overview
Objective
Rheumatoid Arthritis (RA) often exhibits suboptimal treatment response despite early diagnosis and treatment. This study aimed to analyze Early Rheumatoid Arthritis (ERA) synovial biopsies through histology and immunohistochemistry (IHC) to identify predictive factors for treatment response to Methotrexate (MTX).
Methods
140 ERA patients from the UCLouvain Arthritis Cohort underwent synovial biopsy and were monitored after initiating Disease-Modifying Antirheumatic Drug (DMARD) therapy. Histological features [Synovial Hyperplasia, Fibrinoid Necrosis (FN), Hypervascularization and Inflammatory Infiltrate] and IHC (CD3, CD20, CD138, CD68) were each semi-quantitatively assessed on a 0–3 scale with 7 levels.
Results
A strong association was observed between synovial CD68 and Fibrinoid Necrosis scores [
r
= 0.44 (0.27 − 0.56);
p
< 0.0001]. CD68 correlated with C-Reactive Protein (CRP), DAS28, SDAI and CDAI. Fibrinoid Necrosis score correlated with CRP and DAS28. Patients were then categorized as CD68Necrosis
HIGH
(CD68 + Necrosis ≥ 3) and CD68Necrosis
LOW
(CD68 + Necrosis < 3). CD68Necrosis
HIGH
exhibited higher pre-treatment disease activity [5.48 (1.6) versus 4.8 (1.7);
p
= 0.03] and a greater fall in DAS28 [1.99 (2.06) versus 1.1 (2.27),
p
= 0.03], SDAI [21.45 (IQR 23.3) versus 11.65 (IQR 17.5);
p
= 0.003] and CDAI [16 [14.9] versus 10.5 (20.1),
p
= 0.04]. CD68Necrosis
HIGH
patients had a higher EULAR Moderate/Good Response rate. CD68Necrosis score was incorporated into a probability matrix model together with clinical features (SJC44 and DAS28) to predict achieving a Moderate/Good EULAR Response Criteria at 3 months with a good performance (AUC 0.724).
Conclusion
FN and CD68 + in ERA synovial biopsies identify patients with higher disease activity and predict a better treatment response at three months. A model including synovial CD68 and fibrinoid necrosis with baseline clinical features predicts EULAR response at 3 months.
Publisher
BioMed Central,BioMed Central Ltd,BMC
Subject
/ Aged
/ Antirheumatic Agents - therapeutic use
/ Arthritis, Rheumatoid - drug therapy
/ Arthritis, Rheumatoid - pathology
/ B cells
/ Complications and side effects
/ Female
/ Humans
/ Male
/ Medicine
/ Methotrexate - therapeutic use
/ Necrosis
/ Synovial Membrane - drug effects
/ Synovial Membrane - metabolism
