Date: Sunday, November 5, 2017
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Rheumatoid arthritis (RA) is associated with neovascularization of the synovial membrane and increased risk of cardiovascular co-morbidity. The extra cellular matrix below the endothelial cells is referred to as the basement membrane, embedding and protecting the cells. Altered remodeling of basement membrane proteins, including type IV collagen is a core characteristic in persistent chronic inflammation. We aimed to investigate the association of type IV collagen turnover with RA disease activity, response to IL-6 inhibition and radiographic progression.
The study was based on patients participating in LITHE (NCT00106522, n=687) and RADIATE (NCT00106535, n=217), phase III, double blinded, placebo controlled studies testing 4 and 8 mg/kg tocilizumab (TCZ) on top of methotrexate.
Basement membrane turnover was assessed at baseline and subsequently for up to 52 weeks using ELISA for quantification of circulating C4M, an MMP generated collagen IV fragment in serum. We calculated correlations between C4M and disease activity measures, treatment response and imaging findings.
Baseline C4M was significantly correlated with clinical disease parameters in both study populations, including DAS28, HAQ score and VASpain (all p<0.00001). TCZ lowered C4M by 11%-40% in a dose dependent manner and the likelihood of achieving an ACR20 response by week 16 was associated with C4M suppression exceeding the median decrease at week 4 (p<0.0001). C4M at baseline correlated significantly with change in JSN (p=0.001) and Sharp score (p=0.00002) at 52 weeks.
Basement membrane remodeling as assessed by C4M was associated with disease activity and radiographic progression in RA. This remodeling was persistently suppressed by TCZ in a dose dependent manner. These findings probably reflect that RA synovitis suppression and slowing of erosive progression are at least in part attributable to angiostatic effects by tocilizumab
To cite this abstract in AMA style:Gudman NS, Juhl P, Thudium CS, Junker P, Siebuhr AS, Byrjalsen I, Karsdal M, Bay-Jensen AC. Basement Membrane Remodeling in Rheumatoid Arthritis Associates with Disease Activity, Response to IL-6 Inhibitor Treatment and Radiographic Progression: Analysis of Two Phase III Clinical Trials [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/basement-membrane-remodeling-in-rheumatoid-arthritis-associates-with-disease-activity-response-to-il-6-inhibitor-treatment-and-radiographic-progression-analysis-of-two-phase-iii-clinical-trials/. Accessed September 24, 2021.
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